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Cerebral Palsy v1.367 REPS2 Mark Cleghorn gene: REPS2 was added
gene: REPS2 was added to Cerebral Palsy. Sources: Other
Mode of inheritance for gene: REPS2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: REPS2 were set to complex neurodevelopmental disorder MONDO:0100038; Cerebral palsy HP:0100021
Penetrance for gene: REPS2 were set to unknown
Review for gene: REPS2 was set to AMBER
Added comment: REPS2
Hao Hu, Guangzhou Women and Children’s MC
ESHG talk 1/6/24, unpublished

Proposed X-linked cerebral palsy + NDD gene

4 unrelated males with predicted deleterious hemizygous REPS2 variants, 2 PTC, 2 missense. 2 de novo, 2 maternally inherited
Phenotypes: 2 w CP + moderate ID/ASD, 2 w NDD NOS
Variants described:
c.1050_1052delGAA;p.K351del
c.1040T>C; p.I347T
c.962C>G; p.S321C
c.1736delA; p.N579Tfs*17

In vitro assay of above 4 variants suggest reduced REPS2 protein stability
Zebrafish model: REPS2 expressed in neuronal cells, REPS2 knock down have reduced motor activity and abN neuronal morphology
Mouse model hemizygous w one of above variants (not specified): reduced performance in cognitive tasks, abnormal neuronal migration pattern on post mortem examination
Mechanism may relate to dopamine signalling?
Sources: Other
Cerebral Palsy v1.367 TBCK Clare van Eyk gene: TBCK was added
gene: TBCK was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TBCK was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCK were set to PMID: 39213953
Phenotypes for gene: TBCK were set to Hypotonia, infantiale with psychomotor retardation and characteristic facies 3, MIM#616900
Review for gene: TBCK was set to RED
Added comment: Single individual with biallelic variants in TBCK reported in a monocentric cohort study (PMID: 39213953). Clinically, hypotonic CP, DD, muscle weakness, hyperlaxicity, epilepsy.
Sources: Literature
Cerebral Palsy v1.367 TBCD Clare van Eyk gene: TBCD was added
gene: TBCD was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TBCD was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBCD were set to PMID: 39213953
Phenotypes for gene: TBCD were set to Encephalopathy, progressive, early-onset, with brain atrophy and thin corpus callosum MIM#617193
Review for gene: TBCD was set to RED
Added comment: Single individual with homozygous missense variant reported in a monocentric cohort study (PMID: 39213953). Clinically, spastic quadriplegia, DD, ID, regression, focal epilepsy, cerebral atrophy, atrophy corpus callosum and brainstem. Initially diagnosed with CP.
Sources: Literature
Cerebral Palsy v1.367 RTN4IP1 Clare van Eyk gene: RTN4IP1 was added
gene: RTN4IP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RTN4IP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RTN4IP1 were set to PMID: 39213953
Phenotypes for gene: RTN4IP1 were set to Optic atrophy 10 with or without ataxia, impaired intellectual development, and seizures, MIM#616732
Review for gene: RTN4IP1 was set to RED
Added comment: Single individual with biallelic variants in RTN4IP1 reported in a monocentric cohort study (PMID: 39213953). Clinically, ataxia, axial hypotonia, DD, epilepsy, nystagmus, opticus neuropathy, dysmorphic features.
Sources: Literature
Cerebral Palsy v1.367 COQ4 Clare van Eyk gene: COQ4 was added
gene: COQ4 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: COQ4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ4 were set to PMID: 39213953
Phenotypes for gene: COQ4 were set to Coenzyme Q10 deficiency, primary, MIM#616276; Spastic ataxia 10, autosomal recessive, MIM#620666
Review for gene: COQ4 was set to RED
Added comment: Two individuals with homozygous p.Thr77Ile variant reported in a monocentric cohort study (PMID: 39213953), both with spastic diplegia, DD but one also with hearing loss.
Sources: Literature
Cerebral Palsy v1.367 RNU7-1 Clare van Eyk gene: RNU7-1 was added
gene: RNU7-1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RNU7-1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU7-1 were set to PMID: 39213953
Phenotypes for gene: RNU7-1 were set to Aicardi-Goutières syndrome 9, MIM#619487
Review for gene: RNU7-1 was set to AMBER
Added comment: Two individuals with biallelic LP/P variants in RNU7-1 reported in a monocentric cohort study (PMID: 39213953). Both have recurrent RNU7-1 40_47DEL.

One with spastic quadriplegia, epilepsy, DD, hypomyelination, cerebral atrophy, old ishemic lesions, calcifications on CT.

Other with peripheral hypertonia, axial hypotonia, dystonia, calcifications, PVL, delayed myelination.
Sources: Literature
Cerebral Palsy v1.367 KMT2D Clare van Eyk edited their review of gene: KMT2D: Added comment: Additional individual with de novo splice variant reported in a monocentric cohort study (PMID: 39213953). Clinically, hypotonia, DD, ASD, dysmorphic features. No functional assessment of variant impact.; Changed publications: PMID: 38693247, PMID: 39213953
Cerebral Palsy v1.367 CLN6 Clare van Eyk gene: CLN6 was added
gene: CLN6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CLN6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CLN6 were set to PMID: 39213953
Phenotypes for gene: CLN6 were set to Neuronal Ceroid Lipofuscinosis 6, MIM#601780
Review for gene: CLN6 was set to RED
Added comment: Single individual with compound heterozygous LP/P variants in CLN6 reported in a monocentric cohort study (PMID: 39213953). Patient reported to have progressive dystonia, developmental regression, DD, ID, with initial diagnosis of CP.
Sources: Literature
Cerebral Palsy v1.367 SMG8 Clare van Eyk gene: SMG8 was added
gene: SMG8 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SMG8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SMG8 were set to PMID: 39213953
Phenotypes for gene: SMG8 were set to Alzahrani-Kuwahara syndrome, MIM#619268
Review for gene: SMG8 was set to RED
Added comment: Single individual with biallelic variants in SMG8 reported in a monocentric CP cohort study (PMID: 39213953). Clinically, spastic CP with DD, ID, peripheral hypertonia, dysmorphic features.
Sources: Literature
Cerebral Palsy v1.367 CHD3 Clare van Eyk edited their review of gene: CHD3: Added comment: Additional individual with de novo missense variant reported in a monocentric cohort study (PMID: 39213953). Clinically, ataxic CP, DD, ID, bilateral widened frontal subarachnoid space.; Changed publications: PMID: 38168508, PMID: 39213953
Cerebral Palsy v1.367 TSEN54 Clare van Eyk gene: TSEN54 was added
gene: TSEN54 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TSEN54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSEN54 were set to PMID: 39213953
Phenotypes for gene: TSEN54 were set to Pontocerebellar hypoplasia type 2, MIM#277470
Review for gene: TSEN54 was set to RED
Added comment: Two individuals with recurrent homozygous variant reported in a monocentric cohort study (PMID: 39213953). Not clear if they are related.

One with spastic CP, DD, epilepsy, feeding difficulties, behavioral problems, vision problems, pontocerebellar atrophy. Other with spastic CP and axial hypotonia, peripheral hypertonia, DD, ID, cortical visual impairment, pontocerebellar atrophy.
Sources: Literature
Cerebral Palsy v1.367 KCNK9 Clare van Eyk gene: KCNK9 was added
gene: KCNK9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNK9 was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: KCNK9 were set to PMID: 39213953
Phenotypes for gene: KCNK9 were set to Birk-Barel syndrome (KCNK9 imprinting syndrome), MIM#612292
Review for gene: KCNK9 was set to RED
Added comment: Single individual with de novo missense variant reported in a monocentric cohort study (PMID: 39213953). Clinically, hypotonic CP, hyperlaxicity, DD, ID.
Sources: Literature
Cerebral Palsy v1.367 PIK3CA Clare van Eyk gene: PIK3CA was added
gene: PIK3CA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIK3CA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3CA were set to PMID: 39213953
Phenotypes for gene: PIK3CA were set to Megalencephaly-capillary malformation-polymicrogyria syndrome, somatic, MIM#602501
Review for gene: PIK3CA was set to RED
Added comment: Single individual with novel de novo in-frame deletion reported in a monocentric cohort study (PMID: 39213953). Clinically hypotonia, hyperlaxity, bilateral polymicrogyria, incomplete inversion hippocampi, prominent cerebellum.
Sources: Literature
Cerebral Palsy v1.367 ERCC8 Clare van Eyk changed review comment from: An additional individual reported with CP and a homozygous frameshift variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.; to: An additional individual reported with CP and a homozygous frameshift variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Single individual with homozygous splice variant reported in a monocentric cohort study (PMID: 39213953). Clinically, spastic CP with hypertonia, DD, ID, corpus callosum hypoplasia, hyperintensities in the deep white matter.
Cerebral Palsy v1.367 ALDH7A1 Clare van Eyk gene: ALDH7A1 was added
gene: ALDH7A1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ALDH7A1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH7A1 were set to PMID: 39213953
Phenotypes for gene: ALDH7A1 were set to Epilepsy, pyridoxine-dependent, MIM#266100
Review for gene: ALDH7A1 was set to RED
Added comment: Single individual with compound heterozygous varianta reported in a monocentric cohort study (PMID: 39213953). Clinically, spastic CP with mild hypertonia, ASD, ADHD, epilepsy not reported. Movement disorders, including CP in one case, are reported in one study of young adults with PDE-ALDH7A1 (PMID: 35782612).
Sources: Literature
Cerebral Palsy v1.367 BRAF Clare van Eyk gene: BRAF was added
gene: BRAF was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: BRAF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRAF were set to PMID: 39213953
Phenotypes for gene: BRAF were set to Cardiofaciocutaneous syndrome, MIM#115150
Review for gene: BRAF was set to AMBER
Added comment: Two individuals each with a de novo missense variant reported in a monocentric cohort study (PMID: 39213953).

One with spastic CP with spasticity, hypertonia, ASD, PFO, mild pulmonary artery stenosis, failure to thrive, nystagmus, dysmorphic features.

The other with hypotonic CP with axial and peripheral hypotonia, DD, ID, mild pulmonary artery stenosis, dysmorphic features, hypothyroidism, small subacute subdural bleeding, small intraventricular haemorrhage, small cerebellum.
Sources: Literature
Cerebral Palsy v1.367 TRIT1 Clare van Eyk gene: TRIT1 was added
gene: TRIT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRIT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRIT1 were set to PMID: 39213953
Phenotypes for gene: TRIT1 were set to Combined oxidative phosphorylation deficiency 35, MIM#617873
Review for gene: TRIT1 was set to RED
Added comment: Single individual with compound heterozygous variants (nonsense and missense) reported in a monocentric cohort study (PMID: 39213953). Clinically axial hypotonia, peripheral hypertonia, microcephaly, spastic CP, widened ventricular system, widened subarachnoid space.
Sources: Literature
Cerebral Palsy v1.367 KIF5C Clare van Eyk gene: KIF5C was added
gene: KIF5C was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KIF5C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIF5C were set to PMID: 39213953
Phenotypes for gene: KIF5C were set to Cortical dysplasia, complex, with other brain malformations 2 MIM#615282
Review for gene: KIF5C was set to RED
Added comment: Single individual with de novo missense variant reported in a monocentric cohort study (PMID: 39213953). Clinically spastic diplegia, DD, severe ID, epilepsy, polymicrogyria.
Sources: Literature
Cerebral Palsy v1.367 KIAA1109 Clare van Eyk gene: KIAA1109 was added
gene: KIAA1109 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KIAA1109 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIAA1109 were set to PMID: 39213953
Phenotypes for gene: KIAA1109 were set to Alkuraya-Kucinskas syndrome, MIM#617822
Review for gene: KIAA1109 was set to RED
Added comment: Single individual with compound heterozygous variants (1 nonsense, 1 missense) reported in a monocentric cohort study (PMID: 39213953). Clinically West syndrome with evolution to Lennox-Gastaut, severe DD, ID, vision problems, microcephaly, feeding difficulties, spasticity, corpus callosum hypoplasia, cerebral atrophy, heterotopia.
Sources: Literature
Cerebral Palsy v1.367 CYFIP2 Clare van Eyk edited their review of gene: CYFIP2: Added comment: Additional individual with de novo missense variant in CYFIP2 reported in a monocentric cohort study (PMID: 39213953). Clinically ID, spastic quadriplegia, ASD.; Changed rating: AMBER; Changed publications: PMID: 38843839, PMID: 39213953
Cerebral Palsy v1.367 CLCN4 Clare van Eyk edited their review of gene: CLCN4: Added comment: Additional hemizygous male (de novo missense mutation) in monocentric cohort study (PMID: 39213953). Clinically spastic quadriplegia, epilepsy, osteoporosis, cerebral atrophy, corpus callosum hypoplasia.; Changed publications: PMID: 38693247, PMID: 37789889, PMID: 39213953
Cerebral Palsy v1.367 TRIO Clare van Eyk gene: TRIO was added
gene: TRIO was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRIO was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIO were set to PMID: 39213953
Phenotypes for gene: TRIO were set to Intellectual developmental disorder, autosomal dominant 44, with microcephaly MIM#617061
Review for gene: TRIO was set to RED
Added comment: Single individual with de novo missense variant in TRIO reported in a monocentric cohort study (PMID: 39213953). Clinically spastic quadriplegia, microcephaly, cortical visual impairment, Lennox Gastaut epilepsy, cerebral atrophy, megacisterna magna, aberrant skull morphology.
Sources: Literature
Cerebral Palsy v1.367 EBF3 Clare van Eyk gene: EBF3 was added
gene: EBF3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EBF3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EBF3 were set to PMID: 39213953
Phenotypes for gene: EBF3 were set to Hypotonia, ataxia and delayed development syndrome MIM#617330
Review for gene: EBF3 was set to RED
Added comment: Single individual with de novo missense variant in EBF3 reported in a monocentric cohort study (PMID: 39213953). Clinically DD, ataxia, dysarthria, strabism, cortical visual impairment.
Sources: Literature
Cerebral Palsy v1.367 ZMYND11 Clare van Eyk gene: ZMYND11 was added
gene: ZMYND11 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZMYND11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYND11 were set to PMID: 39213953
Phenotypes for gene: ZMYND11 were set to Intellectual developmental disorder 30, MIM#616083
Review for gene: ZMYND11 was set to RED
Added comment: Single individual with novel de novo missense variant and dyskinetic CP with ID, dystonia, peripheral hypertonia and delayed myelination.
Sources: Literature
Cerebral Palsy v1.367 PGAP2 Clare van Eyk gene: PGAP2 was added
gene: PGAP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PGAP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PGAP2 were set to PMID: 39213953
Phenotypes for gene: PGAP2 were set to Hyperphosphatasia with impaired intellectual development syndrome 3, MIM#614207
Review for gene: PGAP2 was set to RED
Added comment: Single individual with homozygous missense variant and severe DD, epilepsy, axial hypotonia, dyskinetic quadriplegia, feeding difficulties.
Sources: Literature
Cerebral Palsy v1.367 PUM1 Clare van Eyk gene: PUM1 was added
gene: PUM1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PUM1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PUM1 were set to PMID: 39213953
Phenotypes for gene: PUM1 were set to Neurodevelopmental disorder with motor abnormalities, seizures, and facial dysmorphism, MIM#620719; Spinocerebellar ataxia 47, MIM#617931
Review for gene: PUM1 was set to RED
Added comment: Single individual with de novo missense variant in PUM1 reported in a monocentric cohort study (PMID: 39213953). Reported with spastic CP, severe DD, epilepsy, microcephaly, cerebral atrophy, thin corpus callosum.
Sources: Literature
Cerebral Palsy v1.367 IREB2 Clare van Eyk gene: IREB2 was added
gene: IREB2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: IREB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IREB2 were set to PMID: 39213953
Phenotypes for gene: IREB2 were set to Neurodegeneration, early-onset, with choreoathetoid movements and microcytic anemia, MIM#618451
Review for gene: IREB2 was set to RED
Added comment: Single individual with compound heterozygous LP/P variants in IREB2 and hypotonic quadriplegia, severe DD, microcytic anemia, elevated ferritin, retinal dystrophy.
Sources: Literature
Cerebral Palsy v1.367 FRRS1L Clare van Eyk reviewed gene: FRRS1L: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 27236917, 39213953; Phenotypes: Developmental and epileptic encephalopathy MIM#616981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.367 CACNA1B Clare van Eyk Deleted their comment
Cerebral Palsy v1.367 CACNA1B Clare van Eyk edited their review of gene: CACNA1B: Added comment: 1 individual reported with biallelic variants (1 missense, 1 splice variant but functional assessment not performed) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Additional case study reporting compound heterozygous frameshift variants in a child with epilepsy and cerebral palsy (PMID: 39005920).
Sources: Literature; Changed publications: PMID: 38693247, PMID: 39005920
Cerebral Palsy v1.367 CACNA1B Clare van Eyk changed review comment from: 1 individual reported with biallelic variants (1 missense, 1 splice) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature; to: 1 individual reported with biallelic variants (1 missense, 1 splice variant but functional assessment not performed) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Additional case study reporting compound heterozygous frameshift variants in a child with epilepsy and cerebral palsy (PMID: 39005920).
Sources: Literature
Cerebral Palsy v1.366 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID: 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Cerebral Palsy v1.364 TRPM3 Clare van Eyk gene: TRPM3 was added
gene: TRPM3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRPM3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRPM3 were set to PMID: 37684057
Phenotypes for gene: TRPM3 were set to Neurodevelopmental disorder with hypotonia, dysmorphic facies, and skeletal anomalies, with or without seizures (NEDFSS), MIM#620224)
Review for gene: TRPM3 was set to RED
Added comment: Single case report of child with a likely pathogenic de novo missense variant in the ion transport domain of TRPM3 and neurodevelopmental delay with CP (PMID: 37684057). Cerebral palsy has not previously been reported.
Sources: Literature
Cerebral Palsy v1.356 ACADM Clare van Eyk reviewed gene: ACADM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38843839; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.356 CYFIP2 Clare van Eyk gene: CYFIP2 was added
gene: CYFIP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CYFIP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CYFIP2 were set to PMID: 38843839
Phenotypes for gene: CYFIP2 were set to Developmental and epileptic encephalopathy 65, MIM#618008
Review for gene: CYFIP2 was set to RED
Added comment: One individual with a complex neurodevelopmental disorder including cerebral palsy reported with a de novo missense variant in CYFIP2 (PMID: 38843839).
Sources: Literature
Cerebral Palsy v1.356 DHPS Clare van Eyk gene: DHPS was added
gene: DHPS was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DHPS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHPS were set to PMID: 30661771; 38843839
Phenotypes for gene: DHPS were set to Neurodevelopmental disorder with seizures and speech and walking impairment (NEDSSWI), MIM#618480
Review for gene: DHPS was set to AMBER
Added comment: NEDSSWI is an autosomal recessive disorder with onset in infancy. In the first case series of 5 patients from 4 families, pregnancy complications including pregnancy-induced hypertension, preeclampsia, oligohydramnios, low blood pressure and premature birth were reported (PMID: 30661771). Patients show global developmental delay and hypotonia, hypertonia, spasticity, or poor coordination. 2 individuals have been reported with a cerebral palsy diagnosis (PMID: 30661771;38843839).
Sources: Literature
Cerebral Palsy v1.356 GFAP Clare van Eyk gene: GFAP was added
gene: GFAP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GFAP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GFAP were set to PMID: 38843839
Phenotypes for gene: GFAP were set to Alexander disease, MIM#203450
Review for gene: GFAP was set to RED
Added comment: One individual with a complex neurodevelopmental disorder including cerebral palsy reported with a de novo missense variant in GFAP (PMID: 38843839). Alexander disease has variable onset and progression, with frequent spasticity and ataxia reported.
Sources: Literature
Cerebral Palsy v1.356 GCH1 Clare van Eyk gene: GCH1 was added
gene: GCH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GCH1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: GCH1 were set to PMID: 21935284; 1899474; 33875303; 34908184
Phenotypes for gene: GCH1 were set to Dystonia, DOPA-responsive, MIM#128230; Hyperphenylalaninemia, BH4-deficient, B, MIM#233910
Review for gene: GCH1 was set to GREEN
Added comment: Mutations in the GTP cyclohydrolase I gene (GCH1) are associated with early onset dopa-responsive dystonia with or without hyperphenylalaninemia which is frequently clinically diagnosed as cerebral palsy (PMID: 21935284; 1899474; 33875303; 34908184).
Sources: Literature
Cerebral Palsy v1.354 ZIC2 Clare van Eyk gene: ZIC2 was added
gene: ZIC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZIC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZIC2 were set to PMID: 38553553
Phenotypes for gene: ZIC2 were set to Holoprosencephaly, MIM#609637
Review for gene: ZIC2 was set to RED
Added comment: Single individual with de novo frameshift deletion described in WGS study of clinically confirmed CP (PMID: 38553553).
Sources: Literature
Cerebral Palsy v1.354 ZDHHC9 Clare van Eyk edited their review of gene: ZDHHC9: Added comment: Additional hemizygous male (maternally inherited) with splice variant described in WGS study of clinically confirmed CP (PMID: 38553553).; Changed publications: PMID: 33528536, PMID: 38693247, PMID: 38553553
Cerebral Palsy v1.348 TRIP12 Clare van Eyk gene: TRIP12 was added
gene: TRIP12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRIP12 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TRIP12 were set to PMID: 36747006
Phenotypes for gene: TRIP12 were set to Intellectual developmental disorder, autosomal dominant 49, MIM#617752
Review for gene: TRIP12 was set to RED
Added comment: Single individual with de novo splice variant described in WGS study of clinically confirmed CP (PMID: 38553553). Motor delays are reported to be common in TRIP12 syndrome.
Sources: Literature
Cerebral Palsy v1.348 SOX2 Clare van Eyk gene: SOX2 was added
gene: SOX2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SOX2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX2 were set to PMID: 38553553
Phenotypes for gene: SOX2 were set to Microphthalmia, syndromic 3; Optic nerve hypoplasia and abnormalities of the central nervous system, MIM#206900
Review for gene: SOX2 was set to RED
Added comment: Single individual with de novo frameshift deletion described in WGS study of clinically confirmed CP (PMID: 38553553). SOX2 disorders are associated with a spectrum of phenotypes which frequently include psychomotor delay, hypotonia, dystonia (including status dystonicus), spastic diplegia/quadriplegia.
Sources: Literature
Cerebral Palsy v1.348 PIK3R2 Clare van Eyk gene: PIK3R2 was added
gene: PIK3R2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIK3R2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PIK3R2 were set to PMID: 38553553
Phenotypes for gene: PIK3R2 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, MIM#603387
Mode of pathogenicity for gene: PIK3R2 was set to Other
Review for gene: PIK3R2 was set to AMBER
Added comment: Single individual with de novo heterozygous p.G373R variant described in WGS study of clinically confirmed CP (PMID: 38553553). This variant is reported multiple times in ClinVar and literature as a recurrent pathogenic activating mutation. Additional case in literature with same variant and spastic hemiplegia (PMID: 26860062). Constitutional and mosaic mutations in PIK3R2 are associated with a range of developmental brain disorders.
Sources: Literature
Cerebral Palsy v1.348 PHKA2 Clare van Eyk gene: PHKA2 was added
gene: PHKA2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PHKA2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PHKA2 were set to PMID: 38553553
Phenotypes for gene: PHKA2 were set to Glycogen storage disease, type IXa, 306000
Review for gene: PHKA2 was set to RED
Added comment: Single individual with de novo hemizygous variant described in WGS study of clinically confirmed CP (PMID: 38553553). Variant has multiple entries in ClinVar - pathogenic/likely pathogenic. GSD9A is primarily associated with liver dysfunction, however dysregulation of glucose metabolism can cause damage to the CNS.
Sources: Literature
Cerebral Palsy v1.348 PHIP Clare van Eyk edited their review of gene: PHIP: Added comment: Additional individual with a pathogenic de novo frameshift insertion described in WGS study of clinically confirmed CP (PMID: 38553553).; Changed rating: GREEN; Changed publications: PMID: 38693247, PMID:33528536, PMID: 38553553
Cerebral Palsy v1.348 PDE10A Clare van Eyk gene: PDE10A was added
gene: PDE10A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PDE10A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: PDE10A were set to PMID: 38553553
Phenotypes for gene: PDE10A were set to Dyskinesia, limb and orofacial, infantile-onset, autosomal recessive, MIM#616921; Striatal degeneration, autosomal dominant, MIM#616922
Review for gene: PDE10A was set to RED
Added comment: Single individual with de novo frameshift deletion described in WGS study of clinically confirmed CP (PMID: 38553553).

Biallelic variants have been reported to cause a hyperkinetic movement disorder with onset in infancy (PMID: 27058446).
Sources: Literature
Cerebral Palsy v1.348 MEF2C Clare van Eyk reviewed gene: MEF2C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38553553; Phenotypes: Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language MIM#613443; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.348 KDM3B Clare van Eyk gene: KDM3B was added
gene: KDM3B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KDM3B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KDM3B were set to PMID: 38553553
Phenotypes for gene: KDM3B were set to Diets-Jongmans syndrome, MIM#618846
Review for gene: KDM3B was set to RED
Added comment: Single individual with de novo likely pathogenic variant described in WGS study of clinically confirmed CP (PMID: 38553553).
Sources: Literature
Cerebral Palsy v1.348 GATAD2B Clare van Eyk edited their review of gene: GATAD2B: Added comment: Additional case with de novo heterozygous LP variant described in WGS study of clinically confirmed CP (PMID: 38553553). Same variant previously reported pathogenic from clinical testing in ClinVar, but no phenotypic data.; Changed publications: PMID: 38693247, PMID: 38553553
Cerebral Palsy v1.348 ERLIN2 Clare van Eyk gene: ERLIN2 was added
gene: ERLIN2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ERLIN2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ERLIN2 were set to PMID: 38553553
Phenotypes for gene: ERLIN2 were set to Spastic paraplegia 18A, autosomal dominant, MIM#620512; Spastic paraplegia 18B, autosomal recessive, MIM#611225
Review for gene: ERLIN2 was set to RED
Added comment: Single individual with homozygous frameshift insertion in ERLIN2 described in WGS study of clinically confirmed CP (PMID: 38553553). Both monoallelic and biallelic variants have been reported to cause hereditary spastic paraplegia.
Sources: Literature
Cerebral Palsy v1.326 THOC2 Zornitza Stark Marked gene: THOC2 as ready
Cerebral Palsy v1.326 THOC2 Zornitza Stark Added comment: Comment when marking as ready: Amber rating due to lack of phenotypic data in the large cohort study.
Cerebral Palsy v1.326 THOC2 Zornitza Stark Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.326 THOC2 Zornitza Stark Classified gene: THOC2 as Amber List (moderate evidence)
Cerebral Palsy v1.326 THOC2 Zornitza Stark Gene: thoc2 has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.315 ZMYM2 Clare van Eyk gene: ZMYM2 was added
gene: ZMYM2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZMYM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZMYM2 were set to PMID: 38168508
Phenotypes for gene: ZMYM2 were set to Neurodevelopmental-craniofacial syndrome with variable renal and cardiac abnormalities, MIM#619522
Review for gene: ZMYM2 was set to RED
Added comment: Single case with de novo pathogenic variant in ZMYM2, diagnosed with spastic quadriplegic cerebral palsy originally attributed to other causes (PMID: 38168508).
Sources: Literature
Cerebral Palsy v1.315 ABHD16A Clare van Eyk gene: ABHD16A was added
gene: ABHD16A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ABHD16A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ABHD16A were set to PMID: 38168508
Phenotypes for gene: ABHD16A were set to Spastic paraplegia 86, autosomal recessive, MIM#619735
Review for gene: ABHD16A was set to RED
Added comment: Single case with homozygous LP variant in ABHD16A, diagnosed with hypotonic-ataxic cerebral palsy with unclear cause (PMID: 38168508). SPG86 is associated with global developmental delay/intellectual disability, progressive spasticity affecting the upper and lower limbs, and corpus callosum and white matter anomalies.
Sources: Literature
Cerebral Palsy v1.315 CHD3 Clare van Eyk gene: CHD3 was added
gene: CHD3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CHD3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD3 were set to PMID: 38168508
Phenotypes for gene: CHD3 were set to Snijders Blok-Campeau syndrome, MIM#618205
Review for gene: CHD3 was set to RED
Added comment: Single case with de novo LP variant in CHD3, diagnosed with spastic hemiplegic cerebral palsy with unclear cause (PMID: 38168508). Causal link not established.
Sources: Literature
Cerebral Palsy v1.315 KCNB1 Clare van Eyk edited their review of gene: KCNB1: Added comment: Additional case with de novo likely pathogenic variant, diagnosed with spastic diplegic cerebral palsy with unclear cause (PMID: 38168508).; Changed rating: GREEN; Changed publications: PMID: 38693247, 38168508
Cerebral Palsy v1.315 POLR2A Clare van Eyk gene: POLR2A was added
gene: POLR2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POLR2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POLR2A were set to PMID: 38168508
Phenotypes for gene: POLR2A were set to Neurodevelopmental disorder with hypotonia and variable intellectual and behavioral abnormalities, MIM#618603
Review for gene: POLR2A was set to RED
Added comment: Single case with de novo LP variant in POLR2A, diagnosed with hypotonic-ataxic cerebral palsy with unclear cause (PMID: 38168508).
Sources: Literature
Cerebral Palsy v1.315 MAPK8IP3 Clare van Eyk gene: MAPK8IP3 was added
gene: MAPK8IP3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MAPK8IP3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAPK8IP3 were set to PMID: 38168508
Phenotypes for gene: MAPK8IP3 were set to Neurodevelopmental disorder with or without variable brain abnormalities, MIM#618443
Review for gene: MAPK8IP3 was set to AMBER
Added comment: Single case with pathogenic MAPK8IP3 variant, inheritance not confirmed, diagnosed with spastic diplegic cerebral palsy with unclear cause (PMID: 38168508).

Additional cases series reported two recurrent de novo missense variants in MAPK8IP3 in 5 individuals from four families with a core set of neurodevelopmental symptoms, including spastic diplegia, intellectual disability, and corpus callosum hypoplasia (PMID: 30945334).
Sources: Literature
Cerebral Palsy v1.315 RARB Clare van Eyk gene: RARB was added
gene: RARB was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RARB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: RARB were set to PMID: 38168508
Phenotypes for gene: RARB were set to Microphthalmia, syndromic 12, MIM#615524
Mode of pathogenicity for gene: RARB was set to Other
Review for gene: RARB was set to RED
Added comment: 1 individual reported with phenotype mimicking CP and recurrent p.Leu213Pro GOF variant in RARB. GOF variants in RARB are associated with severe global developmental delay with progressive motor impairment due to spasticity and/or dystonia (with or without chorea). Biallelic truncating variants also reported to cause microphthalmia and diaphragmatic hernia.
Sources: Literature
Cerebral Palsy v1.315 B4GALNT1 Clare van Eyk edited their review of gene: B4GALNT1: Added comment: Additional case with compound heterozygous variants in B4GALNT1, diagnosed with spastic diplegic cerebral palsy with unclear cause (PMID: 38168508).; Changed rating: AMBER; Changed publications: PMID: 38693247, PMID: 38168508
Cerebral Palsy v1.315 ZDHHC9 Clare van Eyk gene: ZDHHC9 was added
gene: ZDHHC9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZDHHC9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ZDHHC9 were set to PMID: 33528536; PMID: 38693247
Phenotypes for gene: ZDHHC9 were set to Intellectual developmental disorder, X-linked syndromic, Raymond type, MIM#300799
Review for gene: ZDHHC9 was set to AMBER
Added comment: Single males hemizygous for P/LP variants reported in each of 2 large CP sequencing studies (PMID: 33528536; PMID: 38693247). Detailed clinical information not supplied for either. Genome-wide significant burden of rare variants in ZDHHC9 reported in panel resequencing study of CP cohort (PMID: 31700678).
Sources: Literature
Cerebral Palsy v1.315 THOC2 Clare van Eyk gene: THOC2 was added
gene: THOC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: THOC2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: THOC2 were set to PMID: 38168508; PMID: 38693247; PMID: 32116545
Phenotypes for gene: THOC2 were set to Intellectual developmental disorder, X-linked 12, MIM#300957
Review for gene: THOC2 was set to GREEN
Added comment: 3 hemizygous males with pathogenic/likely pathogenic variants reported in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Additional female with cryptogenic spastic quadriplegic CP also reported with heterozygous de novo pathogenic THOC2 variant (PMID: 38168508). Some females reported in literature previously. Dyskinesia, dystonia and spasticity are reported as clinical features in several additional cases in a series (PMID: 32116545).
Sources: Literature
Cerebral Palsy v1.315 TAF1 Clare van Eyk reviewed gene: TAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, X-linked syndromic 33, OMIM #300966, Dystonia-Parkinsonism, X-linked, OMIM #314250; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 PQBP1 Clare van Eyk gene: PQBP1 was added
gene: PQBP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PQBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PQBP1 were set to PMID: 38693247
Phenotypes for gene: PQBP1 were set to Renpenning syndrome, MIM#309500
Review for gene: PQBP1 was set to RED
Added comment: 1 hemizygous male reported with splice variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Spastic diplegia is a common feature in individuals with Renpenning syndrome.
Sources: Literature
Cerebral Palsy v1.315 POLA1 Clare van Eyk gene: POLA1 was added
gene: POLA1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POLA1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: POLA1 were set to PMID: 38693247
Phenotypes for gene: POLA1 were set to Van Esch-O'Driscoll syndrome, MIM#301030
Review for gene: POLA1 was set to AMBER
Added comment: 3 males with hemizygous LOF variants reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Spasticity has been reported as a rare feature of VEODS.
Sources: Literature
Cerebral Palsy v1.315 PHF6 Clare van Eyk gene: PHF6 was added
gene: PHF6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PHF6 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: PHF6 were set to PMID: 38693247
Phenotypes for gene: PHF6 were set to Borjeson-Forssman-Lehmann syndrome, MIM#301900
Review for gene: PHF6 was set to RED
Added comment: Single male proband with hemizygous variant impacting splicing of the first non-coding exon reported in large-scale exome sequencing study (PMID: 38693247). In silico prediction is strong, but functional impact not assessed. Detailed clinical information not supplied. BFLS is characterized by short stature, obesity, hypogonadism, hypotonia, intellectual disability, distinctive facial features, fleshy ears, and finger and toe abnormalities.
Sources: Literature
Cerebral Palsy v1.315 PLP1 Clare van Eyk reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Pelizaeus-Merzbacher disease MIM#312080, Spastic paraplegia 2, X-linked MIM#312920; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 PIGA Clare van Eyk reviewed gene: PIGA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868, Neurodevelopmental disorder with epilepsy and hemochromatosis MIM#301072, Paroxysmal nocturnal hemoglobinuria, somatic MIM#300818; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 OPHN1 Clare van Eyk gene: OPHN1 was added
gene: OPHN1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: OPHN1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: OPHN1 were set to PMID: 38693247
Phenotypes for gene: OPHN1 were set to Intellectual developmental disorder, X-linked syndromic, Billuart type, MIM#300486
Review for gene: OPHN1 was set to RED
Added comment: 1 male with hemizygous variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MRXSBL is associated with generalized hypotonia and delayed psychomotor development from infancy, with some individuals developing ataxia associated with cerebellar hypoplasia.
Sources: Literature
Cerebral Palsy v1.315 MED12 Clare van Eyk changed review comment from: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.

1 additional female with a de novo heterozygous variant reported in large retrospective cohort study of patients with cerebral palsy (PMID 33528536); to: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.

1 additional female with a de novo likely pathogenic heterozygous variant reported in large retrospective cohort study of patients with cerebral palsy (PMID 33528536)
Cerebral Palsy v1.315 MED12 Clare van Eyk reviewed gene: MED12: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID 33528536; Phenotypes: Opitz-Kaveggia syndrome, MIM#305450; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 MED12 Clare van Eyk Deleted their review
Cerebral Palsy v1.315 MED12 Clare van Eyk changed review comment from: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.
Sources: Literature; to: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.

1 additional female with a de novo heterozygous variant reported in large retrospective cohort study of patients with cerebral palsy (PMID 33528536)
Sources: Literature
Cerebral Palsy v1.315 MED12 Clare van Eyk gene: MED12 was added
gene: MED12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: MED12 were set to PMID: 38693247
Phenotypes for gene: MED12 were set to Opitz-Kaveggia syndrome, MIM#305450
Review for gene: MED12 was set to RED
Added comment: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity.
Sources: Literature
Cerebral Palsy v1.315 L1CAM Clare van Eyk reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID 33528536; Phenotypes: CRASH syndrome, MIM# 303350; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 KDM5C Clare van Eyk reviewed gene: KDM5C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534, MONDO:0010355; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 HPRT1 Clare van Eyk reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Hyperuricemia, HRPT-related MIM#300323, Lesch-Nyhan syndrome MIM#300322; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.315 HCFC1 Clare van Eyk gene: HCFC1 was added
gene: HCFC1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HCFC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: HCFC1 were set to PMID: 38693247
Phenotypes for gene: HCFC1 were set to Methylmalonic aciduria and homocysteinemia, cblX type, MIM#309541
Review for gene: HCFC1 was set to AMBER
Added comment: 2 males reported with hemizygous LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MAHCX is characterized by severely delayed psychomotor development apparent in infancy.
Sources: Literature
Cerebral Palsy v1.315 CCDC22 Clare van Eyk changed review comment from: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in RTSC2 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals.
Sources: Literature; to: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in CCDC22 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals.
Sources: Literature
Cerebral Palsy v1.315 FGD1 Clare van Eyk gene: FGD1 was added
gene: FGD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FGD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: FGD1 were set to PMID: 38693247; PMID:33528536
Phenotypes for gene: FGD1 were set to Aarskog-Scott syndrome; Intellectual developmental disorder, X-linked syndromic 16, MIM#305400
Review for gene: FGD1 was set to RED
Added comment: 1 individual reported with hemizygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Additional male with de novo hemizygous pathogenic variant reported in a clinical laboratory referral cohort (PMID:33528536). No clear phenotypic overlap with CP.
Sources: Literature
Cerebral Palsy v1.315 EBP Clare van Eyk gene: EBP was added
gene: EBP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EBP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: EBP were set to PMID: 38693247
Phenotypes for gene: EBP were set to MEND syndrome, MIM#300960
Review for gene: EBP was set to RED
Added comment: 1 individual reported with hemizygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MEND syndrome is associated with severe neurological involvement (e.g. intellectual disability, delayed psychomotor development, seizures, hydrocephalus, cerebellar/corpus callosum hypoplasia, Dandy-Walker malformation, hypotonia).
Sources: Literature
Cerebral Palsy v1.315 CLCN4 Clare van Eyk reviewed gene: CLCN4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 37789889; Phenotypes: Raynaud-Claes syndrome MIM#300114; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.315 CCDC22 Clare van Eyk gene: CCDC22 was added
gene: CCDC22 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CCDC22 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: CCDC22 were set to PMID: 38693247
Phenotypes for gene: CCDC22 were set to Ritscher-Schinzel syndrome 2, MIM#300963
Review for gene: CCDC22 was set to RED
Added comment: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in RTSC2 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals.
Sources: Literature
Cerebral Palsy v1.312 SYNE1 Zornitza Stark Phenotypes for gene: SYNE1 were changed from Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743 to Spinocerebellar ataxia, autosomal recessive 8 MIM#610743
Cerebral Palsy v1.310 TH Zornitza Stark Publications for gene: TH were set to 34788679
Cerebral Palsy v1.309 TH Zornitza Stark Classified gene: TH as Green List (high evidence)
Cerebral Palsy v1.309 TH Zornitza Stark Gene: th has been classified as Green List (High Evidence).
Cerebral Palsy v1.294 ARHGEF9 Clare van Eyk gene: ARHGEF9 was added
gene: ARHGEF9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARHGEF9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ARHGEF9 were set to PMID: 38693247
Phenotypes for gene: ARHGEF9 were set to Developmental and epileptic encephalopathy 8, MIM#300607
Review for gene: ARHGEF9 was set to RED
Added comment: 1 individual reported with hemizygous pathogenic variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Impaired psychomotor development is a feature of DEE8.
Sources: Literature
Cerebral Palsy v1.294 ABCD1 Clare van Eyk gene: ABCD1 was added
gene: ABCD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ABCD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: ABCD1 were set to PMID: 38693247
Phenotypes for gene: ABCD1 were set to Adrenoleukodystrophy, MIM#300100
Review for gene: ABCD1 was set to RED
Added comment: 1 male with hemizygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Variable age of onset, even within same family. Heterozygous females may develop spastic paraparesis with bowel and bladder difficulties.
Sources: Literature
Cerebral Palsy v1.294 SMC1A Clare van Eyk gene: SMC1A was added
gene: SMC1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SMC1A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SMC1A were set to PMID: 38693247; 26358754
Phenotypes for gene: SMC1A were set to Developmental and epileptic encephalopathy 85, with or without midline brain defects, MIM#301044
Review for gene: SMC1A was set to RED
Added comment: 1 male reported with apparently hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). LOF variants thought to be male-lethal. Detailed clinical information not supplied.

1 female in literature with a heterozygous de novo splice site mutation in SMC1A and severe encephalopathy with early-onset epilepsy who developed spastic tetraparesis (PMID: 26358754)
Sources: Literature
Cerebral Palsy v1.294 SLC35A2 Clare van Eyk gene: SLC35A2 was added
gene: SLC35A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC35A2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: SLC35A2 were set to PMID: 38693247
Phenotypes for gene: SLC35A2 were set to Congenital disorder of glycosylation, type IIm, MIM#300896
Review for gene: SLC35A2 was set to RED
Added comment: 1 individual reported with hemizygous stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Variants cause an epileptic encephalopathy which has been associated with ataxia and hypotonia.
Sources: Literature
Cerebral Palsy v1.294 PDHA1 Clare van Eyk reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency MIM#312170; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 PCDH19 Clare van Eyk changed review comment from: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. 1 female with heterozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.; to: 1 female with heterozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Cerebral Palsy v1.294 PCDH19 Clare van Eyk commented on gene: PCDH19: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. 1 female with heterozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Cerebral Palsy v1.294 MECP2 Clare van Eyk reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Encephalopathy, neonatal severe - 300673, Intellectual developmental disorder, X-linked syndromic, Lubs type - 300260, Intellectual developmental disorder, X-linked, syndromic 13 - 300055, Rett syndrome - 312750; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 IQSEC2 Clare van Eyk reviewed gene: IQSEC2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder MIM#309530; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 HUWE1 Clare van Eyk reviewed gene: HUWE1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Turner type, MIM#309590; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 CDKL5 Clare van Eyk reviewed gene: CDKL5: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy 2, MIM#300672; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.294 WDR62 Clare van Eyk gene: WDR62 was added
gene: WDR62 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: WDR62 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR62 were set to PMID: 38693247
Phenotypes for gene: WDR62 were set to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, MIM#604317
Review for gene: WDR62 was set to RED
Added comment: 1 individual reported with biallelic pathogenic variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

MCPH2 is associated with primary microcephaly with variable other neurodevelopmental features. Spastic quadriplegia, hemiplegia, hypertonia are reported.
Sources: Literature
Cerebral Palsy v1.294 VPS53 Clare van Eyk gene: VPS53 was added
gene: VPS53 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: VPS53 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS53 were set to PMID: 38693247
Phenotypes for gene: VPS53 were set to Pontocerebellar hypoplasia, type 2E, MIM#615851
Review for gene: VPS53 was set to RED
Added comment: 1 individual reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Pontocerebellar hypoplasia type 2E is an autosomal recessive neurodegenerative disorder characterized by profound intellectual disability, progressive microcephaly, spasticity, and early-onset epilepsy. 1 family reported with complex hereditary spastic paraparesis phenotype (PMID: 31418091).
Sources: Literature
Cerebral Palsy v1.294 VPS13B Clare van Eyk gene: VPS13B was added
gene: VPS13B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: VPS13B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS13B were set to PMID: 38693247
Phenotypes for gene: VPS13B were set to Cohen syndrome, MIM#216550
Review for gene: VPS13B was set to RED
Added comment: 2 individuals with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.294 TH Clare van Eyk reviewed gene: TH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 28904579; Phenotypes: Segawa syndrome, recessive, MIM#605407; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.294 SYNE1 Clare van Eyk reviewed gene: SYNE1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 30275942; Phenotypes: Spinocerebellar ataxia, autosomal recessive 8 MIM#610743; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.294 SLC25A12 Clare van Eyk gene: SLC25A12 was added
gene: SLC25A12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC25A12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC25A12 were set to PMID: 31403263; PMID: 38693247
Phenotypes for gene: SLC25A12 were set to Developmental and epileptic encephalopathy 39, MIM#612949
Review for gene: SLC25A12 was set to RED
Added comment: 1 patient with novel compound heterozygous variants reported with spastic quadriplegic cerebral palsy (PMID: 31403263). Additional individual reported with homozygous missense variant in large-scale exome sequencing study (PMID: 38693247), however detailed clinical information and functional support for pathogenicity were not supplied.
Sources: Literature
Cerebral Palsy v1.294 RTTN Clare van Eyk gene: RTTN was added
gene: RTTN was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RTTN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RTTN were set to PMID: 38693247
Phenotypes for gene: RTTN were set to Microcephaly, short stature, and polymicrogyria with seizures, MIM#614833
Review for gene: RTTN was set to RED
Added comment: 1 individual reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Hypotonia and spasticity have been reported in MSSP.
Sources: Literature
Cerebral Palsy v1.294 ROGDI Clare van Eyk gene: ROGDI was added
gene: ROGDI was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ROGDI was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ROGDI were set to PMID: 38693247
Phenotypes for gene: ROGDI were set to Kohlschutter-Tonz syndrome, MIM#226750
Review for gene: ROGDI was set to RED
Added comment: 1 individual reported with biallelic pathogenic LOF variants (1 stopgain,1 splice) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

Kohlschutter-Tonz syndrome is characterized by a consistent phenotype of severe global developmental delay, early-onset intractable seizures, progressive spasticity, and amelogenesis imperfecta causing discoloration of both primary and secondary teeth.
Sources: Literature
Cerebral Palsy v1.291 POLG Clare van Eyk gene: POLG was added
gene: POLG was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POLG were set to PMID: 33528536; PMID: 38693247
Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4a, MIM#203700, Mitochondrial DNA Depletion Syndrome 4B, MIM#613662, Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), MIM#607459
Review for gene: POLG was set to AMBER
Added comment: 1 individual reported with biallelic P/LP missense variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Additional individual reported in clinical referral cohort (PMID: 33528536). Mutations in POLG are associated with a wide range of clinical features including lactic acidosis, seizures, ataxia, peripheral neuropathy, developmental delay, myopathy, chronic progressive external ophthalmoplegia, and hepatopathy.
Sources: Literature
Cerebral Palsy v1.291 PLA2G6 Clare van Eyk reviewed gene: PLA2G6: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.291 PIGN Clare van Eyk edited their review of gene: PIGN: Added comment: An additional individual reported with biallelic stopgain variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.; Changed publications: PMID: 33528536, PMID: 34540776, PMID: 38693247
Cerebral Palsy v1.291 PIDD1 Clare van Eyk gene: PIDD1 was added
gene: PIDD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIDD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIDD1 were set to PMID: 38693247
Phenotypes for gene: PIDD1 were set to Intellectual developmental disorder, autosomal recessive 75, with neuropsychiatric features and variant lissencephaly, MIM#619827
Review for gene: PIDD1 was set to RED
Added comment: 1 individual reported with biallelic LOF variants reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. PIDD1 is associated with an intellectual developmental disorder with variant lissencephaly.
Sources: Literature
Cerebral Palsy v1.291 PCLO Clare van Eyk gene: PCLO was added
gene: PCLO was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PCLO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCLO were set to PMID: 38693247
Phenotypes for gene: PCLO were set to Pontocerebellar hypoplasia, type 3, MIM#608027
Review for gene: PCLO was set to RED
Added comment: 1 individual reported with homozygous stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.291 MYO9A Clare van Eyk gene: MYO9A was added
gene: MYO9A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MYO9A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MYO9A were set to PMID: 38693247
Phenotypes for gene: MYO9A were set to Myasthenic syndrome, congenital, 24, presynaptic, MIM#618198
Review for gene: MYO9A was set to RED
Added comment: 2 individuals reported with biallelic P/LP variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.291 PCDH12 Clare van Eyk commented on gene: PCDH12: 2 additional individuals reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Cerebral Palsy v1.291 MUT Clare van Eyk gene: MUT was added
gene: MUT was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MUT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MUT were set to PMID: 38693247
Phenotypes for gene: MUT were set to Methylmalonic aciduria, MIM#251000
Review for gene: MUT was set to AMBER
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Methylmalonic aciduria has a broad clinical spectrum, with neurologic manifestations, such as seizure, encephalopathy, and stroke, frequently reported.
Sources: Literature
Cerebral Palsy v1.291 MOCS1 Clare van Eyk reviewed gene: MOCS1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Molybdenum cofactor deficiency A MIM#252150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.291 MMACHC Clare van Eyk gene: MMACHC was added
gene: MMACHC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MMACHC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MMACHC were set to PMID: 38693247
Phenotypes for gene: MMACHC were set to Methylmalonic aciduria and homocystinuria, cblC type, MIM#277400
Review for gene: MMACHC was set to AMBER
Added comment: 3 individuals reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Variable age at onset with frequent neurological and cardiovascular sequelae.
Sources: Literature
Cerebral Palsy v1.291 MCCC2 Clare van Eyk gene: MCCC2 was added
gene: MCCC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MCCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCCC2 were set to PMID: 38693247
Phenotypes for gene: MCCC2 were set to 3-Methylcrotonyl-CoA carboxylase 2 deficiency, MIM#210210
Review for gene: MCCC2 was set to AMBER
Added comment: 1 individual reported with homozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MCC2D is an autosomal recessive disorder of leucine catabolism. Highly variable clinical phenotype ranging from neonatal onset with severe neurologic involvement to asymptomatic adults. Additional individuals with a clinical diagnosis of CP or overlapping clinical presentation can be found in the literature (e.g. PMID: 9187484, PMID: 10485305)
Sources: Literature
Cerebral Palsy v1.291 LZTR1 Clare van Eyk gene: LZTR1 was added
gene: LZTR1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: LZTR1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LZTR1 were set to PMID: 38693247
Phenotypes for gene: LZTR1 were set to Noonan syndrome 2, MIM#605275
Review for gene: LZTR1 was set to RED
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.291 LRP2 Clare van Eyk gene: LRP2 was added
gene: LRP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: LRP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRP2 were set to PMID: 38693247
Phenotypes for gene: LRP2 were set to Donnai-Barrow syndrome, MIM#222448
Review for gene: LRP2 was set to RED
Added comment: 1 individual reported with compound heterozygous predicted LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. DBS is associated with multiple congenital anomalies.
Sources: Literature
Cerebral Palsy v1.291 LAMA1 Clare van Eyk gene: LAMA1 was added
gene: LAMA1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: LAMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LAMA1 were set to PMID: 38693247
Phenotypes for gene: LAMA1 were set to Poretti-Boltshauser syndrome, MIM#615960
Review for gene: LAMA1 was set to RED
Added comment: 1 individual reported with biallelic pathogenic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Cerebellar cysts and periventricular white matter abnormalities are common imaging findings in Poretti-Boltshauser syndrome.
Sources: Literature
Cerebral Palsy v1.290 KIF14 Clare van Eyk gene: KIF14 was added
gene: KIF14 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KIF14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF14 were set to PMID: 38693247
Phenotypes for gene: KIF14 were set to Microcephaly 20, primary, MIM#617914
Review for gene: KIF14 was set to RED
Added comment: 1 individual reported with biallelic variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.284 Zornitza Stark removed gene:AGA from the panel
Cerebral Palsy v1.283 HSPD1 Clare van Eyk gene: HSPD1 was added
gene: HSPD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HSPD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HSPD1 were set to PMID: 38693247
Phenotypes for gene: HSPD1 were set to Leukodystrophy, hypomyelinating, 4, MIM#612233
Review for gene: HSPD1 was set to RED
Added comment: 1 individual reported with homozygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. HLD4 has been reported to show rapidly progressive prominent spasticity and developmental regression.
Sources: Literature
Cerebral Palsy v1.283 GCDH Clare van Eyk reviewed gene: GCDH: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Glutaricaciduria, type I MIM#231670; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.283 GBA Clare van Eyk gene: GBA was added
gene: GBA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GBA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GBA were set to PMID: 38693247
Phenotypes for gene: GBA were set to Gaucher disease, MIM#231000
Review for gene: GBA was set to RED
Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Gaucher disease can be associated with ataxia, dystonia and spasticity with variable age of onset.
Sources: Literature
Sources: Literature
Cerebral Palsy v1.281 GAMT Clare van Eyk gene: GAMT was added
gene: GAMT was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GAMT was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GAMT were set to PMID: 38693247
Phenotypes for gene: GAMT were set to Cerebral creatine deficiency syndrome 2, MIM#612736
Review for gene: GAMT was set to AMBER
Added comment: 1 individual reported with CP and biallelic variants (missense and stopgain) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Cerebral creatine deficiency syndrome 2 is associated with prominent movement disturbances and can be initially diagnosed as CP (PMID: 31380813).
Sources: Literature
Cerebral Palsy v1.281 FAM20C Clare van Eyk gene: FAM20C was added
gene: FAM20C was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FAM20C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM20C were set to PMID: 38693247
Phenotypes for gene: FAM20C were set to Raine syndrome, MIM#259775
Review for gene: FAM20C was set to RED
Added comment: 1 individual reported with biallelic variants (1 stopgain, 1 frameshift) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Raine syndrome was originally described as a neonatal osteosclerotic bone dysplasia of early and aggressive onset usually resulting in death within the first few weeks of life, however more recently non-lethal cases with a variable spectrum of features including neurological have been described (PMID: 32299476).
Sources: Literature
Cerebral Palsy v1.281 GALC Clare van Eyk gene: GALC was added
gene: GALC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GALC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GALC were set to PMID: 38693247
Phenotypes for gene: GALC were set to Krabbe disease, MIM#245200
Review for gene: GALC was set to AMBER
Added comment: 2 individuals reported with biallelic P/LP variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Krabbe disease is associated with progressive spasticity with variable at age at onset. Later onset can be associated with a slower progression and can mimic CP.
Sources: Literature
Cerebral Palsy v1.275 ERCC8 Clare van Eyk reviewed gene: ERCC8: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Cockayne syndrome MIM#216400; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.275 EPG5 Clare van Eyk gene: EPG5 was added
gene: EPG5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EPG5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EPG5 were set to PMID: 38693247
Phenotypes for gene: EPG5 were set to Vici syndrome, MIM#242840
Review for gene: EPG5 was set to RED
Added comment: 1 individual reported with a homozygous stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Vici syndrome is a neurodevelopmental and immunological disorder affecting multiple systems. Structural abnormalities of the brain along with profound psychomotor retardation have been reported.
Sources: Literature
Cerebral Palsy v1.275 DUOX2 Clare van Eyk gene: DUOX2 was added
gene: DUOX2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DUOX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DUOX2 were set to PMID: 38693247
Phenotypes for gene: DUOX2 were set to Thyroid dyshormonogenesis 6, MIM#607200
Review for gene: DUOX2 was set to RED
Added comment: 1 individual reported with biallelic variants (1 missense, 1 stopgain) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Congenital hypothyroidism is associated with increased risk of cerebral palsy if untreated, amongst other developmental sequelae.
Sources: Literature
Cerebral Palsy v1.275 DIAPH1 Clare van Eyk gene: DIAPH1 was added
gene: DIAPH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DIAPH1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: DIAPH1 were set to PMID: 38693247; 34125151
Phenotypes for gene: DIAPH1 were set to Seizures, cortical blindness, and microcephaly syndrome, MIM#616632
Review for gene: DIAPH1 was set to AMBER
Added comment: 1 individual reported with biallelic LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.

De novo and rare, transmitted damaging variants in DIAPH1 have been reported as a risk factor for Moyamoya disease resulting in ischemic stroke, however CP was not reported as a sequelae in this case series (PMID:34125151).
Sources: Literature
Cerebral Palsy v1.275 DHCR7 Clare van Eyk gene: DHCR7 was added
gene: DHCR7 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DHCR7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DHCR7 were set to PMID: 38693247
Phenotypes for gene: DHCR7 were set to Smith-Lemli-Opitz syndrome, MIM#270400
Review for gene: DHCR7 was set to RED
Added comment: 1 individual reported with biallelic P/LP variants (1 missense, 1 frameshift) in a large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Hypotonia in infancy followed by later hypertonia are described, usually presenting with multiple congenital anomalies.
Sources: Literature
Cerebral Palsy v1.275 DDX59 Clare van Eyk edited their review of gene: DDX59: Changed rating: RED
Cerebral Palsy v1.275 DDX59 Clare van Eyk gene: DDX59 was added
gene: DDX59 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DDX59 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDX59 were set to PMID: 38693247
Phenotypes for gene: DDX59 were set to Orofaciodigital syndrome V, MIM#174300
Added comment: 1 individual reported with biallelic variants (1 missense, 1 frameshift) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. OFD5 has not been previously associated with CP, however white matter abnormalities on MRI have been reported.
Sources: Literature
Cerebral Palsy v1.194 CYP2U1 Clare van Eyk reviewed gene: CYP2U1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spastic paraplegia 56, autosomal recessive, MIM#615030; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.194 COL6A3 Clare van Eyk gene: COL6A3 was added
gene: COL6A3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: COL6A3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COL6A3 were set to PMID: 38693247
Phenotypes for gene: COL6A3 were set to Dystonia 27, MIM#616411
Review for gene: COL6A3 was set to RED
Added comment: 2 individuals reported with biallelic variants in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 CEP290 Clare van Eyk gene: CEP290 was added
gene: CEP290 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CEP290 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CEP290 were set to PMID: 38693247
Phenotypes for gene: CEP290 were set to Joubert syndrome 5, MIM#610188
Review for gene: CEP290 was set to RED
Added comment: 1 individual reported with biallelic variants (1 frameshift insertion, 1 splice) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 CACNA1B Clare van Eyk gene: CACNA1B was added
gene: CACNA1B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CACNA1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CACNA1B were set to PMID: 38693247
Phenotypes for gene: CACNA1B were set to Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements, MIM#618497
Review for gene: CACNA1B was set to RED
Added comment: 1 individual reported with biallelic variants (1 missense, 1 splice) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 B4GALNT1 Clare van Eyk gene: B4GALNT1 was added
gene: B4GALNT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: B4GALNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: B4GALNT1 were set to PMID: 38693247
Phenotypes for gene: B4GALNT1 were set to Spastic paraplegia 26, autosomal recessive, MIM#609195
Review for gene: B4GALNT1 was set to RED
Added comment: 1 individual reported with homozygous frameshift variant in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 ATR Clare van Eyk gene: ATR was added
gene: ATR was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATR were set to PMID: 38693247
Phenotypes for gene: ATR were set to Seckel syndrome, MIM#210600
Review for gene: ATR was set to RED
Added comment: 1 individual reported with biallelic splice variants in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 ASPA Clare van Eyk gene: ASPA was added
gene: ASPA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ASPA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASPA were set to PMID: 38693247
Phenotypes for gene: ASPA were set to Canavan disease, MIM#271900
Review for gene: ASPA was set to RED
Added comment: 1 individual reported with biallelic P/LP variants (1 missense and 1 stopgain) in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.194 AGA Clare van Eyk Deleted their review
Cerebral Palsy v1.194 AGA Clare van Eyk gene: AGA was added
gene: AGA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: AGA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: AGA were set to PMID: 38693247
Phenotypes for gene: AGA were set to Canavan disease, MIM#271900
Review for gene: AGA was set to RED
Added comment: Single individual with biallelic variants (1 missense, 1 stopgain) reported in large-scale CP exome sequencing study (PMID: 38693247). No detailed clinical information provided. Rapid progression typically observed.
Sources: Literature
Cerebral Palsy v1.194 ASL Clare van Eyk gene: ASL was added
gene: ASL was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ASL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ASL were set to PMID: 38693247
Phenotypes for gene: ASL were set to Argininosuccinic aciduria, MIM#207900
Review for gene: ASL was set to RED
Added comment: 1 individual with biallelic P variants reported in large-scale CP exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 ARSA Clare van Eyk gene: ARSA was added
gene: ARSA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARSA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARSA were set to PMID: 38693247
Phenotypes for gene: ARSA were set to Metachromatic leukodystrophy, MIM#250100
Review for gene: ARSA was set to AMBER
Added comment: 3 individuals with biallelic P/LP variants reported in large-scale CP exome sequencing study (PMID: 38693247). No detailed clinical information provided. MLD is associated with progressive neurologic dysfunction, however variable rate of progression.
Sources: Literature
Cerebral Palsy v1.194 ARMC9 Clare van Eyk gene: ARMC9 was added
gene: ARMC9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARMC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARMC9 were set to PMID: 38693247
Phenotypes for gene: ARMC9 were set to Joubert syndrome 30, MIM#617622
Review for gene: ARMC9 was set to RED
Added comment: 1 individual with biallelic variants (1 stopgain, 1 missense) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 ACAD9 Clare van Eyk gene: ACAD9 was added
gene: ACAD9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ACAD9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACAD9 were set to PMID: 38693247
Phenotypes for gene: ACAD9 were set to Mitochondrial complex I deficiency, nuclear type 20, MIM#611126
Review for gene: ACAD9 was set to RED
Added comment: 1 individual with biallelic splice variants reported in large-scale exome sequencing study (PMID: 38693247). No functional assessement reported. No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 AP4M1 Clare van Eyk reviewed gene: AP4M1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spastic paraplegia 50, autosomal recessive, MIM# 612936; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.194 SPTBN2 Clare van Eyk reviewed gene: SPTBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spinocerebellar ataxia 5 MIM#600224, Spinocerebellar ataxia, autosomal recessive 14 MIM#615386; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cerebral Palsy v1.194 ITPR1 Clare van Eyk reviewed gene: ITPR1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spinocerebellar ataxia 29, congenital nonprogressive MIM#117360; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 ZEB2 Clare van Eyk reviewed gene: ZEB2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Mowat-Wilson syndrome, MIM # 235730; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 ZBTB18 Clare van Eyk gene: ZBTB18 was added
gene: ZBTB18 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZBTB18 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZBTB18 were set to PMID: 38693247
Phenotypes for gene: ZBTB18 were set to Intellectual developmental disorder, autosomal dominant 22, MIM#612337
Review for gene: ZBTB18 was set to AMBER
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided. Spasticity, ataxia, hypotonia are reported features, but not diagnosed CP (PMID: 27598823).
Sources: Literature
Cerebral Palsy v1.194 UBE3A Clare van Eyk reviewed gene: UBE3A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Angelman syndrome, MIM #105830; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 TUBG1 Clare van Eyk gene: TUBG1 was added
gene: TUBG1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBG1 were set to PMID: 38693247
Phenotypes for gene: TUBG1 were set to Cortical dysplasia, complex, with other brain malformations 4, MIM#615412
Review for gene: TUBG1 was set to RED
Added comment: 1 individual with a LP missense variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 TUBB4A Clare van Eyk reviewed gene: TUBB4A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Dystonia 4, torsion, autosomal dominant, MIM#128101, Leukodystrophy, hypomyelinating, 6, MIM#612438; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 TUBB2B Clare van Eyk reviewed gene: TUBB2B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Cortical dysplasia, complex, with other brain malformations 7, MIM#610031; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 TSHR Clare van Eyk gene: TSHR was added
gene: TSHR was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TSHR was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSHR were set to PMID: 38693247
Phenotypes for gene: TSHR were set to Hyperthyroidism, nonautoimmune, MIM#609152
Review for gene: TSHR was set to RED
Added comment: 2 individuals with LP variants reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 TSC2 Clare van Eyk gene: TSC2 was added
gene: TSC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TSC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSC2 were set to PMID: 38693247
Phenotypes for gene: TSC2 were set to Tuberous sclerosis-2, MIM#613254
Review for gene: TSC2 was set to RED
Added comment: 1 individual with splice variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 TOR1A Clare van Eyk gene: TOR1A was added
gene: TOR1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TOR1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TOR1A were set to PMID: 38693247
Phenotypes for gene: TOR1A were set to Dystonia-1, torsion, MIM#128100
Review for gene: TOR1A was set to RED
Added comment: 1 individual with heterozygous in-frame deletion reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 TGM6 Clare van Eyk gene: TGM6 was added
gene: TGM6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TGM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TGM6 were set to PMID: 38693247
Phenotypes for gene: TGM6 were set to Spinocerebellar ataxia 35, MIM#613908
Review for gene: TGM6 was set to AMBER
Added comment: 2 individuals with LP/P variants reported in large-scale exome sequencing study (PMID: 38693247). No additional clinical information provided.

Age of onset of SCA35 is reported to be teenage-adult years.
Sources: Literature
Cerebral Palsy v1.194 TCF4 Clare van Eyk reviewed gene: TCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Pitt-Hopkins syndrome, MIM# 610954; Mode of inheritance: None
Cerebral Palsy v1.194 TBX6 Clare van Eyk gene: TBX6 was added
gene: TBX6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TBX6 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TBX6 were set to PMID: 38693247
Phenotypes for gene: TBX6 were set to Spondylocostal dysostosis 5, MIM#122600
Review for gene: TBX6 was set to RED
Added comment: 1 individual with likely pathogenic missense variant reported in large-scale exome sequencing study (PMID: 38693247). No additional clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 TBR1 Clare van Eyk gene: TBR1 was added
gene: TBR1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TBR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBR1 were set to PMID: 38693247
Phenotypes for gene: TBR1 were set to Intellectual developmental disorder with autism and speech delay, MIM#606053
Review for gene: TBR1 was set to RED
Added comment: 1 individual with mono-allelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247). No additional clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 TANC2 Clare van Eyk gene: TANC2 was added
gene: TANC2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TANC2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TANC2 were set to PMID: 38693247
Phenotypes for gene: TANC2 were set to Intellectual developmental disorder with autistic features and language delay, with or without seizures, MIM#618906
Review for gene: TANC2 was set to RED
Added comment: 1 individual with mono-allelic splice variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SYNGAP1 Clare van Eyk reviewed gene: SYNGAP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, autosomal dominant 5, MIM#612621; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 SPAST Clare van Eyk reviewed gene: SPAST: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 SOX10 Clare van Eyk gene: SOX10 was added
gene: SOX10 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SOX10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SOX10 were set to PMID: 38693247
Phenotypes for gene: SOX10 were set to PCWH syndrome, MIM#609136; Waardenburg syndrome, type 2E, with or without neurologic involvement, MIM#611584
Review for gene: SOX10 was set to RED
Added comment: 1 individual with mono-allelic LOF (stopgain variant) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SON Clare van Eyk reviewed gene: SON: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 37168776; Phenotypes: ZTTK syndrome MIM#617140; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 SMC3 Clare van Eyk gene: SMC3 was added
gene: SMC3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SMC3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMC3 were set to PMID: 38693247
Phenotypes for gene: SMC3 were set to Cornelia de Lange syndrome 3, MIM#610759
Review for gene: SMC3 was set to RED
Added comment: 1 individual with mono-allelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SMARCA4 Clare van Eyk gene: SMARCA4 was added
gene: SMARCA4 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SMARCA4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA4 were set to PMID: 38693247
Phenotypes for gene: SMARCA4 were set to Coffin-Siris syndrome 4, MIM#614609
Review for gene: SMARCA4 was set to RED
Added comment: 1 individual with mono-allelic splice variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 SMARCA2 Clare van Eyk gene: SMARCA2 was added
gene: SMARCA2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SMARCA2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SMARCA2 were set to PMID: 38693247
Phenotypes for gene: SMARCA2 were set to Blepharophimosis-impaired intellectual development syndrome, MIM#619293; Nicolaides-Baraitser syndrome, MIM#601358
Review for gene: SMARCA2 was set to RED
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SLC6A5 Clare van Eyk gene: SLC6A5 was added
gene: SLC6A5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC6A5 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SLC6A5 were set to PMID: 38693247
Phenotypes for gene: SLC6A5 were set to Hyperekplexia 3, MIM#614618
Review for gene: SLC6A5 was set to AMBER
Added comment: 2 individuals with mono-allelic pathogenic stopgain variants reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SLC1A2 Clare van Eyk gene: SLC1A2 was added
gene: SLC1A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLC1A2 were set to PMID: 38693247; PMID:33528536
Phenotypes for gene: SLC1A2 were set to Developmental and epileptic encephalopathy 41, MIM#617105
Review for gene: SLC1A2 was set to AMBER
Added comment: 1 individual with mono-allelic stopgain variant reported in large-scale exome sequencing study (PMID: 38693247). 1 individual with mono-allelic de novo missense variant reported in large retrospective analysis of WES data from a clinical laboratory referral cohort and healthcare cohort (PMID:33528536).
Sources: Literature
Cerebral Palsy v1.194 SIK1 Clare van Eyk gene: SIK1 was added
gene: SIK1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SIK1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SIK1 were set to PMID: 38693247
Phenotypes for gene: SIK1 were set to Developmental and epileptic encephalopathy 30, MIM#616341
Review for gene: SIK1 was set to RED
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SGCE Clare van Eyk gene: SGCE was added
gene: SGCE was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SGCE was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SGCE were set to PMID: 38693247
Phenotypes for gene: SGCE were set to Dystonia-11, myoclonic, MIM#159900
Review for gene: SGCE was set to RED
Added comment: 1 individual with mono-allelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 PHIP Clare van Eyk edited their review of gene: PHIP: Added comment: 2 individuals reported with cerebral palsy and P/LP splice variants in PHIP in a large retrospective analysis of WES data from a clinical laboratory referral cohort and healthcare cohort (PMID:33528536).; Changed rating: AMBER; Changed publications: PMID: 38693247, PMID:33528536
Cerebral Palsy v1.194 SETD2 Clare van Eyk gene: SETD2 was added
gene: SETD2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SETD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETD2 were set to PMID: 38693247; 33528536
Phenotypes for gene: SETD2 were set to Intellectual developmental disorder, autosomal dominant 70, MIM#620157; Luscan-Lumish syndrome, MIM#61683; Rabin-Pappas syndrome, MIM#620155
Review for gene: SETD2 was set to AMBER
Added comment: 1 individual with mono-allelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.

1 individual reported with cerebral palsy and maternally inherited pathogenic stopgain variant in a large retrospective analysis of WES data from a clinical laboratory referral cohort and healthcare cohort (PMID:33528536).
Sources: Literature
Cerebral Palsy v1.194 SETBP1 Clare van Eyk gene: SETBP1 was added
gene: SETBP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SETBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SETBP1 were set to PMID: 38693247
Phenotypes for gene: SETBP1 were set to Intellectual developmental disorder, autosomal dominant 29, MIM#616078; Schinzel-Giedion midface retraction syndrome, MIM#269150
Review for gene: SETBP1 was set to RED
Added comment: 1 individual with mono-allelic stopgain variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 SCN8A Clare van Eyk reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: None; Publications: 38693247; Phenotypes: Epileptic encephalopathy 13 MIM# 614558, Cognitive impairment with or without cerebellar ataxia MIM# 614306; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.194 SCN2A Clare van Eyk edited their review of gene: SCN2A: Added comment: 3 additional individuals with mono-allelic P/LP variants (2 missense, 1 stopgain) reported in large-scale exome sequencing study (PMID: 38693247).; Changed publications: 33528536, 29761117, 34114234, 38693247
Cerebral Palsy v1.194 SCN1A Clare van Eyk commented on gene: SCN1A: 1 additional individual with LP missense variant reported in large-scale exome sequencing study (PMID: 38693247).
Cerebral Palsy v1.194 PPM1D Clare van Eyk gene: PPM1D was added
gene: PPM1D was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PPM1D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PPM1D were set to PMID: 38693247
Phenotypes for gene: PPM1D were set to Jansen-de Vries syndrome, MIM#617450
Review for gene: PPM1D was set to RED
Added comment: 1 individual with mono-allelic splice variant reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 PHIP Clare van Eyk gene: PHIP was added
gene: PHIP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PHIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PHIP were set to PMID: 38693247
Phenotypes for gene: PHIP were set to Chung-Jansen syndrome, MIM#617991
Review for gene: PHIP was set to RED
Added comment: 1 individual with monoallelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.

LOF variants in PHIP are associated with developmental delay, intellectual disability, anxiety, hypotonia, poor balance, obesity, and dysmorphic features.
Sources: Literature
Cerebral Palsy v1.194 PACS1 Clare van Eyk gene: PACS1 was added
gene: PACS1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PACS1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PACS1 were set to PMID: 38693247
Phenotypes for gene: PACS1 were set to Schuurs-Hoeijmakers syndrome, MIM#615009
Review for gene: PACS1 was set to AMBER
Added comment: 2 individuals with mono-allelic variants (1 missense, 1 splice) reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided. PACS1 variants are associated with hypotonia starting in the new-born period which may persist throughout childhood.
Sources: Literature
Cerebral Palsy v1.194 NSD2 Clare van Eyk gene: NSD2 was added
gene: NSD2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NSD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSD2 were set to PMID: 38693247
Phenotypes for gene: NSD2 were set to Rauch-Steindl syndrome, MIM#619695
Review for gene: NSD2 was set to RED
Added comment: 1 individual with mono-allelic LOF variant (frameshift) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 NSD1 Clare van Eyk gene: NSD1 was added
gene: NSD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NSD1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSD1 were set to PMID: 38693247
Phenotypes for gene: NSD1 were set to Sotos syndrome, MIM#117550
Review for gene: NSD1 was set to RED
Added comment: 2 individuals with mono-allelic LOF (1 stopgain, 1 frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247). No additional clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 NR2F1 Clare van Eyk gene: NR2F1 was added
gene: NR2F1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NR2F1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NR2F1 were set to PMID: 38693247
Phenotypes for gene: NR2F1 were set to Bosch-Boonstra-Schaaf optic atrophy syndrome, MIM#615722; NR2F1-related neurodevelopmental disorder
Review for gene: NR2F1 was set to RED
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 NOTCH1 Clare van Eyk gene: NOTCH1 was added
gene: NOTCH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NOTCH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NOTCH1 were set to PMID: 38693247
Phenotypes for gene: NOTCH1 were set to Adams-Oliver syndrome 5, MIM#616028
Review for gene: NOTCH1 was set to AMBER
Added comment: 3 individuals with mono-allelic P/LP variants (1 splice, 1 stopgain, 1 missense) reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 NFIB Clare van Eyk gene: NFIB was added
gene: NFIB was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NFIB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIB were set to PMID: 38693247
Phenotypes for gene: NFIB were set to Macrocephaly, acquired, with impaired intellectual development, MIM#618286
Review for gene: NFIB was set to RED
Added comment: 1 individual with mono-allelic LOF (frameshift deletion) reported in large-scale exome sequencing study (PMID: 38693247).
Sources: Literature
Cerebral Palsy v1.194 NFE2L2 Clare van Eyk gene: NFE2L2 was added
gene: NFE2L2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NFE2L2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFE2L2 were set to PMID: 38693247
Phenotypes for gene: NFE2L2 were set to Immunodeficiency, developmental delay, and hypohomocysteinemia , MIM#617744
Review for gene: NFE2L2 was set to RED
Added comment: 1 individual with mono-allelic stopgain variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.194 NEFL Clare van Eyk gene: NEFL was added
gene: NEFL was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NEFL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NEFL were set to Charcot-Marie-Tooth disease, dominant intermediate G, MIM#617882
Review for gene: NEFL was set to RED
Added comment: 1 individual with mono-allelic stopgain variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.194 NALCN Clare van Eyk edited their review of gene: NALCN: Added comment: 1 additional individual with mono-allelic LP splice variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.; Changed publications: PMID:33528536, PMID:34364746, PMID: 38693247
Cerebral Palsy v1.193 MYH2 Clare van Eyk gene: MYH2 was added
gene: MYH2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MYH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MYH2 were set to PMID: 38693247
Phenotypes for gene: MYH2 were set to Congenital myopathy 6 with ophthalmoplegia, MIM#605637
Review for gene: MYH2 was set to RED
Added comment: 1 individual with mono-allelic stopgain variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 MFN2 Clare van Eyk reviewed gene: MFN2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2A2A MIM#609260, Hereditary motor and sensory neuropathy VIA MIM#601152; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 MED13L Clare van Eyk gene: MED13L was added
gene: MED13L was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MED13L was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MED13L were set to PMID: 38693247
Phenotypes for gene: MED13L were set to Impaired intellectual development and distinctive facial features with or without cardiac defects, OMIM#616789
Review for gene: MED13L was set to AMBER
Added comment: 1 individual with mono-allelic stopgain variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 MBD5 Clare van Eyk gene: MBD5 was added
gene: MBD5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MBD5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MBD5 were set to PMID: 38693247
Phenotypes for gene: MBD5 were set to Intellectual developmental disorder, autosomal dominant 1, MIM#156200
Review for gene: MBD5 was set to AMBER
Added comment: 1 individuals with mono-allelic stopgain variants and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 MACF1 Clare van Eyk gene: MACF1 was added
gene: MACF1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MACF1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MACF1 were set to PMID: 38693247
Phenotypes for gene: MACF1 were set to Lissencephaly 9 with complex brainstem malformation, MIM#618325
Review for gene: MACF1 was set to AMBER
Added comment: 1 individual with mono-allelic LP missense variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided. Spasticity and involuntary movements described in some cases.
Sources: Literature
Cerebral Palsy v1.193 KMT2D Clare van Eyk gene: KMT2D was added
gene: KMT2D was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KMT2D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2D were set to PMID: 38693247
Phenotypes for gene: KMT2D were set to Kabuki syndrome 1, MIM#147920
Review for gene: KMT2D was set to AMBER
Added comment: 2 individuals with mono-allelic splice variants and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 KMT2B Clare van Eyk reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Dystonia 28, childhood-onset MIM#617284, Intellectual developmental disorder, autosomal dominant MIM#619934; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KMT2A Clare van Eyk reviewed gene: KMT2A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Wiedemann-Steiner syndrome - #605130; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KIF1A Clare van Eyk reviewed gene: KIF1A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spastic paraplegia 30, autosomal dominant, MIM# 610357; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KIDINS220 Clare van Eyk reviewed gene: KIDINS220: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spastic paraplegia, intellectual disability, nystagmus, and obesity - #617296; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KCNT1 Clare van Eyk reviewed gene: KCNT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy MIM#614959; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KCNQ5 Clare van Eyk gene: KCNQ5 was added
gene: KCNQ5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNQ5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNQ5 were set to PMID: 38693247
Phenotypes for gene: KCNQ5 were set to Intellectual developmental disorder, autosomal dominant 46, MIM#617601
Review for gene: KCNQ5 was set to AMBER
Added comment: 1 individual with mono-allelic splice variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.

Additional individuals described have motor delays, mostly with hypotonia (PMID: 35583973).
Sources: Literature
Cerebral Palsy v1.193 KCNQ3 Clare van Eyk gene: KCNQ3 was added
gene: KCNQ3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNQ3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNQ3 were set to PMID: 38693247
Phenotypes for gene: KCNQ3 were set to Seizures, benign neonatal, 2, MIM#121201
Review for gene: KCNQ3 was set to RED
Added comment: 1 individual with mono-allelic frameshift deletion and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided. No evidence for clinical overlap.
Sources: Literature
Cerebral Palsy v1.193 KCNH1 Clare van Eyk gene: KCNH1 was added
gene: KCNH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNH1 were set to PMID: 38693247
Phenotypes for gene: KCNH1 were set to Temple-Baraitser syndrome, MIM#611816; Zimmermann-Laband syndrome 1, MIM#135500
Review for gene: KCNH1 was set to AMBER
Added comment: 4 individuals with mono-allelic LP missense variants and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 KCNB1 Clare van Eyk reviewed gene: KCNB1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy 26, MIM#616056; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 KAT6B Clare van Eyk gene: KAT6B was added
gene: KAT6B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KAT6B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT6B were set to PMID: 38693247
Phenotypes for gene: KAT6B were set to SBBYSS syndrome, MIM#603736; Genitopatellar syndrome, MIM#606170
Review for gene: KAT6B was set to AMBER
Added comment: 1 individual with mono-allelic stopgain variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 KAT6A Clare van Eyk reviewed gene: KAT6A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Arboleda-Tham syndrome MIM#616268; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 HIVEP2 Clare van Eyk gene: HIVEP2 was added
gene: HIVEP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HIVEP2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HIVEP2 were set to PMID: 38693247
Phenotypes for gene: HIVEP2 were set to Intellectual developmental disorder, autosomal dominant 43, MIM#616977
Review for gene: HIVEP2 was set to RED
Added comment: 1 individual with mono-allelic stopgain variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 HECW2 Clare van Eyk reviewed gene: HECW2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Neurodevelopmental disorder with hypotonia, seizures, and absent language, MIM#617268; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 GRIN2A Clare van Eyk gene: GRIN2A was added
gene: GRIN2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GRIN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIN2A were set to PMID: 38693247
Phenotypes for gene: GRIN2A were set to Epilepsy, focal, with speech disorder and with or without impaired intellectual development, MIM#245570
Review for gene: GRIN2A was set to RED
Added comment: 1 individual with mono-allelic frameshift deletion and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 GNB1 Clare van Eyk reviewed gene: GNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, autosomal dominant 42 MIM# 616973; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 GNAO1 Clare van Eyk reviewed gene: GNAO1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 GATAD2B Clare van Eyk gene: GATAD2B was added
gene: GATAD2B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GATAD2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GATAD2B were set to PMID: 38693247
Phenotypes for gene: GATAD2B were set to GAND syndrome, MIM#615076
Review for gene: GATAD2B was set to AMBER
Added comment: 2 individuals with mono-allelic stopgain variants and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided. Some clinical overlap with CP.
Sources: Literature
Cerebral Palsy v1.193 GABBR2 Clare van Eyk gene: GABBR2 was added
gene: GABBR2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GABBR2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABBR2 were set to PMID: 38693247
Phenotypes for gene: GABBR2 were set to Developmental and epileptic encephalopathy 59, MIM#617904; Neurodevelopmental disorder with poor language and loss of hand skills, MIM#617903
Review for gene: GABBR2 was set to AMBER
Added comment: 1 individual with mono-allelic LP missense variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 FUS Clare van Eyk gene: FUS was added
gene: FUS was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FUS was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FUS were set to PMID: 38693247
Phenotypes for gene: FUS were set to Essential tremor, MIM#614782
Review for gene: FUS was set to RED
Added comment: 1 individual with mono-allelic splice variant and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 FGFR1 Clare van Eyk gene: FGFR1 was added
gene: FGFR1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FGFR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FGFR1 were set to PMID: 38693247
Phenotypes for gene: FGFR1 were set to Hartsfield syndrome, MIM#615465
Review for gene: FGFR1 was set to RED
Added comment: 1 individual reported with mono-allelic splice variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 EZH2 Clare van Eyk gene: EZH2 was added
gene: EZH2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EZH2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EZH2 were set to PMID: 38693247
Phenotypes for gene: EZH2 were set to Weaver syndrome, MIM#277590
Review for gene: EZH2 was set to RED
Added comment: 1 individual reported with mono-allelic LP variant (frameshift deletion) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 EHMT1 Clare van Eyk gene: EHMT1 was added
gene: EHMT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EHMT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EHMT1 were set to PMID: 38693247
Phenotypes for gene: EHMT1 were set to Kleefstra syndrome, MIM#610253
Review for gene: EHMT1 was set to RED
Added comment: Single individual reported with mono-allelic splice variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 EEF1A2 Clare van Eyk reviewed gene: EEF1A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy MIM#616409; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 DYRK1A Clare van Eyk reviewed gene: DYRK1A: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, MIM#614104; Mode of inheritance: None
Cerebral Palsy v1.193 DNMT3A Clare van Eyk gene: DNMT3A was added
gene: DNMT3A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DNMT3A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNMT3A were set to PMID: 38693247
Phenotypes for gene: DNMT3A were set to Heyn-Sproul-Jackson syndrome, MIM#618724; Tatton-Brown-Rahman syndrome, MIM#615879
Review for gene: DNMT3A was set to AMBER
Added comment: 2 individuals reported with mono-allelic frameshift deletions in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 DNM2 Clare van Eyk gene: DNM2 was added
gene: DNM2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DNM2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DNM2 were set to PMID: 38693247
Phenotypes for gene: DNM2 were set to Charcot-Marie-Tooth disease, axonal type 2M, MIM#606482
Review for gene: DNM2 was set to RED
Added comment: 1 individual reported with mono-allelic missense variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 DLG4 Clare van Eyk changed review comment from: 1 individual reported with mono-allelic stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature; to: 1 individual reported with mono-allelic stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 DLG4 Clare van Eyk gene: DLG4 was added
gene: DLG4 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DLG4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DLG4 were set to PMID: 38693247
Phenotypes for gene: DLG4 were set to Intellectual developmental disorder, autosomal dominant 62, MIM#618793
Review for gene: DLG4 was set to AMBER
Added comment: 1 individual reported with mono-allelic stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 DCC Clare van Eyk gene: DCC was added
gene: DCC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DCC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DCC were set to PMID: 38693247
Phenotypes for gene: DCC were set to Mirror movements 1 and/or agenesis of the corpus callosum, MIM#157600
Review for gene: DCC was set to RED
Added comment: 1 individual reported with mono-allelic stopgain in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CUL3 Clare van Eyk gene: CUL3 was added
gene: CUL3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CUL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CUL3 were set to PMID: 38693247
Phenotypes for gene: CUL3 were set to Neurodevelopmental disorder with or without autism or seizures, MIM#619239, Pseudohypoaldosteronism, type IIE, MIM#614496
Review for gene: CUL3 was set to AMBER
Added comment: 1 individual reported with mono-allelic splice variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CTNNB1 Clare van Eyk reviewed gene: CTNNB1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Neurodevelopmental disorder with spastic diplegia and visual defects, MIM#615075; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 CTCF Clare van Eyk gene: CTCF was added
gene: CTCF was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CTCF was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTCF were set to PMID: 38693247
Phenotypes for gene: CTCF were set to Intellectual developmental disorder, autosomal dominant 21, MIM#615502
Review for gene: CTCF was set to RED
Added comment: 1 individual reported with mono-allelic stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CTBP1 Clare van Eyk reviewed gene: CTBP1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome MIM#617915; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 COL4A1 Clare van Eyk changed review comment from: Additional 2 individuals reproted with mono-allelic P/LP variants (1 frameshift deletion and 1 stopgain) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.; to: Additional 2 individuals reported with mono-allelic P/LP variants (1 frameshift deletion and 1 stopgain) in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Cerebral Palsy v1.193 CREBBP Clare van Eyk reviewed gene: CREBBP: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Menke-Hennekam syndrome MIM#618332, Rubinstein-Taybi syndrome MIM#180849; Mode of inheritance: None
Cerebral Palsy v1.193 COL4A2 Clare van Eyk reviewed gene: COL4A2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Brain small vessel disease 2 MIM# 614483; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.193 COL4A1 Clare van Eyk reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Brain small vessel disease MIM#614483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 CLCN7 Clare van Eyk gene: CLCN7 was added
gene: CLCN7 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CLCN7 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: CLCN7 were set to PMID: 38693247
Phenotypes for gene: CLCN7 were set to Hypopigmentation, organomegaly, and delayed myelination and development, MIM#175780; Osteopetrosis, autosomal recessive 4; OPTB4, MIM#602727
Review for gene: CLCN7 was set to RED
Added comment: 1 individual with homozygous splice variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Bi-allelic variants have been reported to cause osteopetrosis.
Sources: Literature
Cerebral Palsy v1.193 CHD7 Clare van Eyk gene: CHD7 was added
gene: CHD7 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CHD7 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD7 were set to PMID: 38693247
Phenotypes for gene: CHD7 were set to CHARGE syndrome, MIM#608892
Review for gene: CHD7 was set to AMBER
Added comment: 2 individuals with mono-allelic LOF variants (1 stopgain, 1 splicing) reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CHD4 Clare van Eyk gene: CHD4 was added
gene: CHD4 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CHD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD4 were set to PMID: 38693247
Phenotypes for gene: CHD4 were set to Sifrim-Hitz-Weiss syndrome, MIM#617159
Review for gene: CHD4 was set to AMBER
Added comment: 2 individuals with mono-allelic missense variants reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CHCHD10 Clare van Eyk gene: CHCHD10 was added
gene: CHCHD10 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CHCHD10 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHCHD10 were set to PMID: 38693247
Phenotypes for gene: CHCHD10 were set to Myopathy, isolated mitochondrial, MIM#616209
Review for gene: CHCHD10 was set to AMBER
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CAMK2G Clare van Eyk gene: CAMK2G was added
gene: CAMK2G was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CAMK2G was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2G were set to PMID: 38693247
Phenotypes for gene: CAMK2G were set to Intellectual developmental disorder, autosomal dominant 59, MIM#618522
Review for gene: CAMK2G was set to AMBER
Added comment: 1 individual with mono-allelic missense variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CAMK2B Clare van Eyk gene: CAMK2B was added
gene: CAMK2B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CAMK2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMK2B were set to PMID: 38693247
Phenotypes for gene: CAMK2B were set to Intellectual developmental disorder, autosomal dominant 54, MIM#617799
Review for gene: CAMK2B was set to AMBER
Added comment: 1 individual with mono-allelic splice variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied.
Sources: Literature
Cerebral Palsy v1.193 CACNA1G Clare van Eyk gene: CACNA1G was added
gene: CACNA1G was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CACNA1G was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1G were set to PMID: 38693247
Phenotypes for gene: CACNA1G were set to Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficits, MIM#618087
Review for gene: CACNA1G was set to GREEN
Added comment: 5 individuals with mono-allelic LP missense variants reported in large-scale exome sequencing study (PMID: 38693247). Ataxia, spasticity and dystonia are reported features of SCA42ND.
Sources: Literature
Cerebral Palsy v1.193 CACNA1D Clare van Eyk gene: CACNA1D was added
gene: CACNA1D was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CACNA1D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1D were set to PMID: 38693247; 23913001
Phenotypes for gene: CACNA1D were set to Primary aldosteronism, seizures and neurologic abnormalities; PASNA, MIM#615474
Mode of pathogenicity for gene: CACNA1D was set to Other
Review for gene: CACNA1D was set to AMBER
Added comment: 1 individual with mono-allelic LP missense variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clincal data.

1 individual described previously with cerebral palsy and a de novo heterozygous gain-of-function missense mutation (PMID: 23913001).
Sources: Literature
Cerebral Palsy v1.193 CACNA1A Clare van Eyk reviewed gene: CACNA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy MIM#617106, Episodic ataxia MIM#108500, familial hemiplegic Migraine MIM#141500 and MIM#141500, Spinocerebellar ataxia MIM#183086; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 BSCL2 Clare van Eyk gene: BSCL2 was added
gene: BSCL2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: BSCL2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BSCL2 were set to PMID: 38693247
Phenotypes for gene: BSCL2 were set to Spastic paraplegia 17, MIM#270685
Review for gene: BSCL2 was set to AMBER
Added comment: Single individual reported with mono-allelic LP frameshift deletion reported in large-scale exome sequencing study (PMID: 38693247). No detailed clinical information provided.
Sources: Literature
Cerebral Palsy v1.193 AUTS2 Clare van Eyk reviewed gene: AUTS2: Rating: ; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, autosomal dominant 26, MIM# 615834; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 ASXL3 Clare van Eyk reviewed gene: ASXL3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID:33528536, PMID: 35863334; Phenotypes: Bainbridge-Ropers syndrome, MIM#615485; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 ATP6V1A Clare van Eyk gene: ATP6V1A was added
gene: ATP6V1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATP6V1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP6V1A were set to PMID: 38693247
Phenotypes for gene: ATP6V1A were set to Developmental and epileptic encephalopathy 93, MIM#618012
Review for gene: ATP6V1A was set to AMBER
Added comment: 1 individual with mono-allelic LP missense variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clincal information not supplied. Spastic quadriparesis and dyskinesia are reported features of DEE93.
Sources: Literature
Cerebral Palsy v1.193 ATP1A3 Clare van Eyk edited their review of gene: ATP1A3: Added comment: Additional 5 individuals with mono-allelic LP missense variants reported in large-scale exome sequencing study (PMID: 38693247).; Changed publications: 33528536, 30542205, 38693247; Changed mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 ATP1A2 Clare van Eyk gene: ATP1A2 was added
gene: ATP1A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATP1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP1A2 were set to PMID: 38693247
Phenotypes for gene: ATP1A2 were set to Alternating hemiplegia of childhood 1, MIM#104290
Review for gene: ATP1A2 was set to AMBER
Added comment: 1 individual with monoallelic missense variant reported in large-scale exome sequencing study. Detailed clinical data not provided.
Sources: Literature
Cerebral Palsy v1.193 ATL1 Clare van Eyk edited their review of gene: ATL1: Added comment: Additional 3 individuals with mono-allelic LP missense variants reported in large-scale exome sequencing study (PMID: 38693247).; Changed publications: PMID: 33528536, PMID: 34321325, PMID: 38693247
Cerebral Palsy v1.193 ASXL3 Clare van Eyk Deleted their review
Cerebral Palsy v1.193 ASXL3 Clare van Eyk edited their review of gene: ASXL3: Added comment: 1 additional individual with mono-allelic LOF (frameshift insertion) reported in large-scale exome sequencing study.; Changed publications: PMID: 38693247
Cerebral Palsy v1.193 ARID2 Clare van Eyk reviewed gene: ARID2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Coffin-Siris syndrome 6, MIM#617808; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.193 ARID1B Clare van Eyk gene: ARID1B was added
gene: ARID1B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID1B were set to PMID: 38693247
Phenotypes for gene: ARID1B were set to Coffin-Siris syndrome 1, MIM#135900
Review for gene: ARID1B was set to AMBER
Added comment: 1 individual with mono-allelic frameshift deletion and cerebral palsy reported in large-scale exome sequencing study. Detailed clinical information not provided.
Sources: Literature
Cerebral Palsy v1.193 AHDC1 Clare van Eyk reviewed gene: AHDC1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Xia-Gibbs syndrome, MIM#615829; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.191 SPTAN1 Zornitza Stark Phenotypes for gene: SPTAN1 were changed from Developmental and epileptic encephalopathy 5; OMIM #613477; Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related to Developmental and epileptic encephalopathy 5; OMIM #613477; Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related; Autosomal dominant spastic paraplegia-91, with or without cerebellar ataxia (SPG91), MIM#620538
Cerebral Palsy v1.190 SPTAN1 Zornitza Stark reviewed gene: SPTAN1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Autosomal dominant spastic paraplegia-91, with or without cerebellar ataxia (SPG91), MIM#620538; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.190 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580 to ATR-X-related syndrome MONDO:0016980
Cerebral Palsy v1.189 ATRX Zornitza Stark edited their review of gene: ATRX: Changed phenotypes: ATR-X-related syndrome MONDO:0016980
Cerebral Palsy v1.187 ESAM Luisa Weiss changed review comment from: Lecca et al. reported 13 individuals from 8 families (4 of which coming from the same geographical region) with a severe neurodevelopmental disorder. Although no formal diagnosis of CP was made, all patients had spasticity and most patients showed spastic tetraparesis. Many patients showed additional phenotypic features (like dysmorphism). All mutations were predicted to be Loss of function mutations.

ESAM encodes an endothelial cell adhesion molecule. A recurrent variant (c.115del;p.(Arg39Glyfs∗33)) was functionally analyzed and showed to impair the in vitro tubulogenic process of endothelial colony-forming cells and to caus lack of ESAM expression in the capillary endothelial cells of damaged brain.
Sources: Literature; to: Lecca et al. reported 13 individuals from 8 families (4 of which coming from the same geographical region) with a severe neurodevelopmental disorder. Although no formal diagnosis of CP was made, all patients had spasticity and most patients showed spastic tetraparesis. Many patients showed additional phenotypic features (like dysmorphism). All mutations were predicted to be Loss of function mutations.

ESAM encodes an endothelial cell adhesion molecule. A recurrent variant (c.115del;p.(Arg39Glyfs∗33)) was functionally analyzed and showed to impair the in vitro tubulogenic process of endothelial colony-forming cells and to cause lack of ESAM expression in the capillary endothelial cells of damaged brain.
Sources: Literature
Cerebral Palsy v1.187 ESAM Luisa Weiss gene: ESAM was added
gene: ESAM was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ESAM were set to 36996813
Phenotypes for gene: ESAM were set to Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity MIM#620371
Review for gene: ESAM was set to GREEN
Added comment: Lecca et al. reported 13 individuals from 8 families (4 of which coming from the same geographical region) with a severe neurodevelopmental disorder. Although no formal diagnosis of CP was made, all patients had spasticity and most patients showed spastic tetraparesis. Many patients showed additional phenotypic features (like dysmorphism). All mutations were predicted to be Loss of function mutations.

ESAM encodes an endothelial cell adhesion molecule. A recurrent variant (c.115del;p.(Arg39Glyfs∗33)) was functionally analyzed and showed to impair the in vitro tubulogenic process of endothelial colony-forming cells and to caus lack of ESAM expression in the capillary endothelial cells of damaged brain.
Sources: Literature
Cerebral Palsy v1.186 SYNE1 Zornitza Stark reviewed gene: SYNE1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Arthrogryposis multiplex congenita 3, myogenic type MIM#618484, Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998, Spinocerebellar ataxia, autosomal recessive 8 MIM#610743; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.185 ADNP Luisa Weiss edited their review of gene: ADNP: Added comment: In addition to the previous cases, there is one case report of a boy with the full phenotypic picture of Helsmoortel-van der Aa syndrome and hypotonic cerebral palsy. Note that hypotonia is one feature of Helsmoortel-van der Aa syndrome, but hypotonic cerebral palsy seems to be rare.; Changed rating: GREEN; Changed publications: 29780943; Changed phenotypes: Helsmoortel-van der Aa syndrome MIM#615873
Cerebral Palsy v1.185 SYNE1 Luisa Weiss Deleted their comment
Cerebral Palsy v1.185 SYNE1 Luisa Weiss edited their review of gene: SYNE1: Added comment: Two cases each in two larger CP cohort studies, one with ataxic and one with spastic CP, with biallelic SYNE1 mutations.
In addition, one case report of an 18-year-old girl with CP and a heterozygous SYNE1-mutation. Not that this patient had a history of perinatal distress and asphyxia. The SYNE1 mutation was discovered at the age of 18 years due to a hypertrophic cardiomyopathy. It is uncertain whether the SYNE1 mutation is the cause for the CP.; Changed rating: GREEN; Changed publications: 34321325, 34816117, 31110749; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.178 HPDL Clare van Eyk reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35985664, PMID: 33634263, PMID: 32707086; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities MIM#619026; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.178 AGAP1 Clare van Eyk changed review comment from: An additional three patients with heterozygous microdeletions and phenotypic overlap with previously described patients, but none with a CP diagnosis (PMID:36778426). Overall 4/10 patients with an AGAP1 variant have CP, however not all of these were classified as pathogenic and 2/3 of the new microdeletions are inherited suggesting incomplete penetrance. Authors show that mutant Drosophila have increased lethality from exposure to environmental insult.; to: An additional three patients with heterozygous microdeletions and phenotypic overlap with previously described patients, but none with a CP diagnosis (PMID:36778426, PMID: 37470098). Overall 4/10 patients with an AGAP1 variant have CP, however not all of these were classified as pathogenic and 2/3 of the new microdeletions are inherited suggesting incomplete penetrance. Authors show that mutant Drosophila have increased lethality from exposure to environmental insult.
Cerebral Palsy v1.178 AGAP1 Clare van Eyk reviewed gene: AGAP1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 36778426; Phenotypes: cerebral palsy, intellectual disability, autism; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.174 TMX2 Zornitza Stark reviewed gene: TMX2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity MIM#618730; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.174 TH Zornitza Stark Marked gene: TH as ready
Cerebral Palsy v1.174 TH Zornitza Stark Gene: th has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.174 TH Zornitza Stark Classified gene: TH as Amber List (moderate evidence)
Cerebral Palsy v1.174 TH Zornitza Stark Gene: th has been classified as Amber List (Moderate Evidence).
Cerebral Palsy v1.171 TEP1 Zornitza Stark commented on gene: TEP1: Uncertain if these are risk alleles vs indicative of a monogenic disorder. Note LoF variants in gnomad. As this was a cohort study, inheritance of these variants is unknown.
Cerebral Palsy v1.171 TEP1 Zornitza Stark reviewed gene: TEP1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Cerebral palsy, MONDO:0006497, TEP1-related; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.169 TANGO2 Zornitza Stark reviewed gene: TANGO2: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration MIM#616878; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.146 TSC1 Luisa Weiss gene: TSC1 was added
gene: TSC1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TSC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TSC1 were set to 29706646; 34788679; 25817843
Phenotypes for gene: TSC1 were set to Focal cortical dysplasia, type II, somatic MIM#607341; Lymphangioleiomyomatosis MIM#606690; Tuberous sclerosis-1 MIM#191100
Review for gene: TSC1 was set to AMBER
Added comment: Two patients in large cohort studies of children with cryptogenic CP and maternally inherited mutation in TSC1, parents were mildly affected. In addition, one patient with a VUS in TSC1 with cortical and movement abnormalities, but no clinical diagnosis of TS.
Sources: Literature
Cerebral Palsy v1.146 TRAPPC9 Luisa Weiss gene: TRAPPC9 was added
gene: TRAPPC9 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TRAPPC9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TRAPPC9 were set to 33528536; 34540776; 36475161
Phenotypes for gene: TRAPPC9 were set to Intellectual developmental disorder, autosomal recessive MIM#13 613192
Review for gene: TRAPPC9 was set to GREEN
Added comment: Two larger CP cohort studies with one patient each harboring biallelic TRAPPC9 mutations. No phenotypic information is given. In addition, one case report of a girl with CP and intellectual disability and biallelic TRAPPC9 mutations.
Sources: Literature
Cerebral Palsy v1.146 TMX2 Luisa Weiss gene: TMX2 was added
gene: TMX2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TMX2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TMX2 were set to 31735293
Phenotypes for gene: TMX2 were set to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity MIM#618730
Added comment: Vandervore et al. published a larger study of several patients with neurological impariment and biallelic TMX2 mutations. 8 individuals out of 5 families had previously been diagnosed with CP. Most patients had severely impaired development and epilepsy.
Sources: Literature
Cerebral Palsy v1.146 TH Luisa Weiss gene: TH was added
gene: TH was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TH were set to 34788679
Phenotypes for gene: TH were set to Segawa syndrome, recessive MIM#605407
Review for gene: TH was set to AMBER
Added comment: 2 individual cases in one large Chinese CP cohort study, both with compound heterozygous mutations.
Sources: Literature
Cerebral Palsy v1.146 TEP1 Luisa Weiss gene: TEP1 was added
gene: TEP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TEP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TEP1 were set to 34543729
Review for gene: TEP1 was set to GREEN
Added comment: Wang et al. screened a large cohort of more than 600 CP patients from China and found several variants in TEP1, 11 of which were LoF, while no LoF variant was found in the control cohort. These children all had spastic CP. Among these 11 children, 6 children had birth asphyxia and neonatal encephalopathy. Compared to the total group with birth asphyxia (71/667), 6 patients with TEP1 LOF mutations had a significantly greater risk of birth asphyxia. They confirmed TEP1 as a risk factor for CP by cytological and animal models.
Sources: Literature
Cerebral Palsy v1.146 TANGO2 Luisa Weiss gene: TANGO2 was added
gene: TANGO2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TANGO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TANGO2 were set to 33528536; 34364746
Phenotypes for gene: TANGO2 were set to Metabolic encephalomyopathic crises, recurrent, with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration MIM#616878
Review for gene: TANGO2 was set to GREEN
Added comment: 3 individual patients in two large CP cohort study, both with biallelic larger deletions encompassing TANGO2. Phenotypic information is only given for one patient, this one showed slowly progressive spastic paraplegia and ataxia.
Sources: Literature
Cerebral Palsy v1.146 SYNGAP1 Luisa Weiss gene: SYNGAP1 was added
gene: SYNGAP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SYNGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SYNGAP1 were set to 33528536; 31700678
Phenotypes for gene: SYNGAP1 were set to Intellectual developmental disorder, autosomal dominant 5 MIM#612621
Review for gene: SYNGAP1 was set to GREEN
Added comment: Moreno de Luca et al. found 3 heterozygous de novo SYNGAP1 mutations in a large CP cohort study. In addition, van Eyk et al. found one non-maternally inherited VUS in a child with CP in a cohort study.
Sources: Literature
Cerebral Palsy v1.146 SYNE1 Luisa Weiss gene: SYNE1 was added
gene: SYNE1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SYNE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SYNE1 were set to 34321325; 34816117
Phenotypes for gene: SYNE1 were set to Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743
Review for gene: SYNE1 was set to AMBER
Added comment: Two cases each in two larger CP cohort studies, one with ataxic and one with spastic CP, with biallelic SYNE1 mutations.
Sources: Literature
Cerebral Palsy v1.146 SUOX Luisa Weiss gene: SUOX was added
gene: SUOX was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SUOX were set to 27289259; 34540776
Phenotypes for gene: SUOX were set to Sulfite oxidase deficiency MIM#272300
Review for gene: SUOX was set to GREEN
Added comment: Zaki et al. presented 3 individual cases in a larger cohort study harboring biallelic SUOX mutations and presenting with spastic quadriparesis, even though no formal CP diagnosis was given. In addition, two additional cases of patients with homozygous mutations in SUOX from a larger cohort study from Iran.
Sources: Literature
Cerebral Palsy v1.146 STAMBP Luisa Weiss gene: STAMBP was added
gene: STAMBP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: STAMBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: STAMBP were set to 33528536; 23542699
Phenotypes for gene: STAMBP were set to Microcephaly-capillary malformation syndrome MIM#614261
Review for gene: STAMBP was set to GREEN
Added comment: 2 cases in a larger CP cohort study with homozygous missense mutations in STAMBP, no phenotypic information is given.
McDonnell et al. (23542699) presented a large cohort of previously published and unpublished patients with microcephaly-capillary malformation syndrome, which all had cutaneous abnormalities, developmental delay and epilepsy, but 8 of which presented with spastic quadriparesis. Overlap with CP is possible; however, additional phenotypic features seem to be present in any case.
Sources: Literature
Cerebral Palsy v1.146 ST3GAL5 Luisa Weiss gene: ST3GAL5 was added
gene: ST3GAL5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ST3GAL5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ST3GAL5 were set to 34540776; 30185102; 25131622; 24026681
Phenotypes for gene: ST3GAL5 were set to Salt and pepper developmental regression syndrome MIM#609056
Review for gene: ST3GAL5 was set to GREEN
Added comment: Several reports on patients with different forms of CP (dystonic, quadriplegic or spastic) later found to harbor biallelic ST3GAL5 mutations. One patient in a larger CP cohort (34540776) with a homozygous VUS, others with pathogenic mutations. Note that the patients which were presented with photographs all showed cutaneous abnormalities as well.
Sources: Literature
Cerebral Palsy v1.146 SPTBN2 Luisa Weiss reviewed gene: SPTBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31066025, 25981959, 31721007; Phenotypes: Spinocerebellar ataxia 5 MIM#600224, Spinocerebellar ataxia, autosomal recessive 14 MIM#615386; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Cerebral Palsy v1.146 SPTBN2 Luisa Weiss Deleted their review
Cerebral Palsy v1.146 SPTBN2 Luisa Weiss gene: SPTBN2 was added
gene: SPTBN2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SPTBN2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: SPTBN2 were set to 31066025; 25981959; 31721007
Phenotypes for gene: SPTBN2 were set to Spinocerebellar ataxia 5 MIM#600224; Spinocerebellar ataxia, autosomal recessive 14 MIM#615386
Added comment: 5 patients presented in an overview study with ataxic CP and heterozygous (4/5) or biallelic SPTBN2 (1/5) mutations. In addition, one more case report and another case in a larger CP cohort study, all children presenting with ataxic CP.
Note both heterozygous and biallelic mutations have been reported to cause ataxic CP in children, even though heterozygous mutations have previously been associated with adult onset spinocerebellar ataxia.
Sources: Literature
Cerebral Palsy v1.144 SPR Luisa Weiss gene: SPR was added
gene: SPR was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SPR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SPR were set to 33528536; 34540776; 22522443
Phenotypes for gene: SPR were set to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency MIM#612716
Review for gene: SPR was set to GREEN
Added comment: Two large CP cohort studies with one case each presenting with CP and biallelic SPR mutations. In one large study from 2012, 43 individuals with Sepiapterin reductase deficiency (SRD) were clinically analyzed, diagnoses of cerebral palsy (CP) were common, both hypotonic and dystonic.
Sources: Literature
Cerebral Palsy v1.144 SPATA5 Luisa Weiss gene: SPATA5 was added
gene: SPATA5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SPATA5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5 were set to 33528536
Phenotypes for gene: SPATA5 were set to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities MIM#616577
Review for gene: SPATA5 was set to GREEN
Added comment: 4 individual cases in one large CP cohort study with biallelic SPATA5 mutations. Spasticity has been described in other patients as well while developmental delay seems to be mostly present.
Sources: Literature
Cerebral Palsy v1.144 SMARCB1 Luisa Weiss reviewed gene: SMARCB1: Rating: AMBER; Mode of pathogenicity: None; Publications: 33528536, 34114234; Phenotypes: Coffin-Siris syndrome 3 MIM#614608, Rhabdoid tumors, somatic MIM#609322; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.144 SLITRK2 Luisa Weiss gene: SLITRK2 was added
gene: SLITRK2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLITRK2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLITRK2 were set to 35840571
Phenotypes for gene: SLITRK2 were set to Intellectual developmental disorder, X-linked MIM#301107
Review for gene: SLITRK2 was set to GREEN
Added comment: Case study of several patients harboring SLITRK2 variants and neurodevelopmental delay. Three patients reported with spasticity, diplegic cerebral palsy and dystonic diplegia, respectively. Functional tests show impaired neuronal function and knock-out mice showed abnormal gait.
Sources: Literature
Cerebral Palsy v1.144 SLC5A6 Luisa Weiss gene: SLC5A6 was added
gene: SLC5A6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC5A6 were set to 33528536; 21112253; 33098801
Phenotypes for gene: SLC5A6 were set to Parkinsonism-dystonia, infantile, 1 MIM#613135
Review for gene: SLC5A6 was set to GREEN
Added comment: 21112253 presents a clinical overview of 11 children with biallelic SLC6A3 mutations, 7 of which were initially diagnosed with CP. In addition, two more CP cohort studies with one patient each harboring SLC6A3 mutations.
Sources: Literature
Cerebral Palsy v1.144 SLC16A2 Luisa Weiss gene: SLC16A2 was added
gene: SLC16A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC16A2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC16A2 were set to 33528536; 35076175; 25280894
Phenotypes for gene: SLC16A2 were set to Allan-Herndon-Dudley syndrome MIM#300523
Review for gene: SLC16A2 was set to GREEN
Added comment: Four individual cases in three large CP cohort studies presenting as dystonic or spastic CP. Mutations described were both nonsense and missense mutations and could be inherited maternally or de novo.
Sources: Literature
Cerebral Palsy v1.144 SLC13A5 Luisa Weiss gene: SLC13A5 was added
gene: SLC13A5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SLC13A5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC13A5 were set to 34364746; 34540776
Phenotypes for gene: SLC13A5 were set to Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905
Review for gene: SLC13A5 was set to AMBER
Added comment: Two large case studies with one patient described each harboring homozygous SLC13A5 variants, however, in PMID 34540776 this variant was defined as a VUS rather than a pathogenic mutation.
In other described cases epilepsy and ID seem to be the main phenotypic features, while ataxia and spasticity have been desribed.
Sources: Literature
Cerebral Palsy v1.144 SHANK3 Luisa Weiss reviewed gene: SHANK3: Rating: AMBER; Mode of pathogenicity: None; Publications: 33528536, 33098801; Phenotypes: Phelan-McDermid syndrome MIM#606232; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.144 SEPSECS Luisa Weiss gene: SEPSECS was added
gene: SEPSECS was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SEPSECS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SEPSECS were set to 33528536; 35252561; 34540776; 36085396
Phenotypes for gene: SEPSECS were set to Pontocerebellar hypoplasia type 2D MIM#613811
Review for gene: SEPSECS was set to GREEN
Added comment: Biallelic SEPSECS mutations have been described to cause Pontocerebellar hypoplasia type 2D, which usually presents with progressive microcephaly, progressive brain atrophy, ID and variable seizures and movement disorders.
There have been two cases in two large CP cohort studies (33528536, 34540776) which have been proven to harbor biallelic SEPSECS variants, however, in PMID 34540776 these can only be formally classified as VUS. In addition, there is a case report (PMID 35252561) of a man presenting with no CP but spastic paraparesis and only slow disease progression in adult life (patient 48 years old at time of presentation). PMID 36085396 provides a literature review of described PCD2D patients, 72.7% of which have presented with spastic or dystonic quadriplegia, so there is significant phenotypic overlap with CP.
Sources: Literature
Cerebral Palsy v1.144 SATB2 Luisa Weiss gene: SATB2 was added
gene: SATB2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SATB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SATB2 were set to 33528536; 35076175
Phenotypes for gene: SATB2 were set to Glass syndrome MIM#612313
Review for gene: SATB2 was set to GREEN
Added comment: 4 patients in 3 large CP cohort studies were found to have heterozygous de novo SATB2 mutations, three of which were nonsense and one was a missense mutation. Note that in one patient an additional acute perinatal event (neonatal compartment syndrome, intracranial hemorrhage) was present which might have added to the CP phenotype.
Sources: Literature
Cerebral Palsy v1.144 SACS Luisa Weiss gene: SACS was added
gene: SACS was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SACS were set to 33528536; 34816117; 29997391
Phenotypes for gene: SACS were set to Spastic ataxia, Charlevoix-Saguenay type MIM#270550
Review for gene: SACS was set to GREEN
Added comment: Multiple large and small cohort studies with more than 3 individual patients initially diagnosed as cerebral palsy and later diagnosed with biallelic SACS mutations. SACS is a known disease gene for spastic ataxia of Charlevoix-Saguenay, which can resemble CP but usually has a progressive course of disease.
Sources: Literature
Cerebral Palsy v1.144 RARS2 Luisa Weiss gene: RARS2 was added
gene: RARS2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RARS2 were set to 34077496; 34717047
Phenotypes for gene: RARS2 were set to Pontocerebellar hypoplasia, type 6 MIM#611523
Review for gene: RARS2 was set to GREEN
Added comment: Two male patients in a large CP cohort study with either spastic quadriplegic or dyskinetic CP. Both frameshift and missense mutations have been described.
PMID 34717047 presents a good overview of published cases with RARS2 mutations. Even though none of them were officially diagnosed with cerebral palsy, many showed progressive movement disorders like spastic quadriplegia, thus possibly presenting as CP.
Sources: Literature
Cerebral Palsy v1.144 RAB3GAP1 Luisa Weiss gene: RAB3GAP1 was added
gene: RAB3GAP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RAB3GAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAB3GAP1 were set to 33528536; 16532399; 27081543
Phenotypes for gene: RAB3GAP1 were set to Martsolf syndrome 2 MIM#619420; Warburg micro syndrome MIM#600118
Review for gene: RAB3GAP1 was set to GREEN
Added comment: Multiple case reports of patients with either Martsolf syndrome or Warburg micro syndrome and spastic diplegia or cerebral palsy, but all patients also presented with eye phenotype. In addition, two individuals in a large CP cohort study (no additional phenotypic information given).
Sources: Literature
Cerebral Palsy v1.144 PTPN23 Luisa Weiss gene: PTPN23 was added
gene: PTPN23 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PTPN23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PTPN23 were set to 31395947; 25558065; 34064836
Phenotypes for gene: PTPN23 were set to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity MIM#618890
Review for gene: PTPN23 was set to AMBER
Added comment: Biallelic PTPN23 mutations have been associated with neurodevelopmental delay and structural brain abnormalities in an initial study of 7 patients. In this cohort, one had the initial diagnosis of cerebral palsy (patient 6), but one other patient (patient 4) showed spasticity and contractures and thus phenotypic overlap. In addition, this study referred to another study (25558065), in which a family with PTPN23 mutations was described. Even though in PMID:31395947 this family was described as having CP, this cannot be confirmed in the initial report. Note that final exon frameshift mutations in PTPN23 have been associated complex hereditary spastic paraplegia which might hint to a phenotypic overlap to CP.
Sources: Literature
Cerebral Palsy v1.144 PTPN11 Luisa Weiss gene: PTPN11 was added
gene: PTPN11 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PTPN11 were set to 33528536; 23799168
Phenotypes for gene: PTPN11 were set to LEOPARD syndrome 1 MIM#151100; Leukemia, juvenile myelomonocytic, somatic MIM#607785; Metachondromatosis MIM#156250; Noonan syndrome MIM#163950
Review for gene: PTPN11 was set to GREEN
Added comment: One case report of a girl with hearing loss and CP later diagnosed as having a heterozygous de novo missense mutation in PTPN11. In addition, two individuals in a large CP cohort study with heterozygous missense PTPN11 mutations. No information about inheritance is given in these cases. Note that there is no information about additional phenotypic features in these two cases, but the girl in the case report presented with the typical clinical picture of Noonan Syndrome with multiple lentigines (NSML, formerly known as Leopard syndrome).
Sources: Literature
Cerebral Palsy v1.142 PROC Zornitza Stark Phenotypes for gene: PROC were changed from Thrombophilia due to protein C deficiency, autosomal recessive, MIM# 612304 to Thrombophilia 3 due to protein C deficiency MIM#176860; Thrombophilia 3 due to protein C deficiency MIM#612304
Cerebral Palsy v1.140 PROC Zornitza Stark Mode of inheritance for gene: PROC was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.138 POMGNT1 Zornitza Stark Phenotypes for gene: POMGNT1 were changed from Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 MIM# 253280; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3 MIM#613151; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157; Retinitis pigmentosa 76 MIM#617123 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 MIM# 253280; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3 MIM#613151; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157
Cerebral Palsy v1.133 PRUNE1 Luisa Weiss gene: PRUNE1 was added
gene: PRUNE1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PRUNE1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PRUNE1 were set to 33528536; 35379233
Phenotypes for gene: PRUNE1 were set to Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MIM#617481
Review for gene: PRUNE1 was set to GREEN
Added comment: Case report of one consanguineous Iranian family with two children affected with spastic quadriplegic CP and a homozygous start loss of PRUNE1. The children also showed hypotonia and cerebellar atrophy. In addition, two additional cases in one large CP cohort study, one with homozygous mutation the other with compound heterozygous mutation/deletion.
Sources: Literature
Cerebral Palsy v1.133 PROC Luisa Weiss reviewed gene: PROC: Rating: GREEN; Mode of pathogenicity: None; Publications: 31700678, 20187890, 34531397; Phenotypes: Thrombophilia 3 due to protein C deficiency MIM#176860, Thrombophilia 3 due to protein C deficiency MIM#612304; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.133 POMGNT1 Luisa Weiss gene: POMGNT1 was added
gene: POMGNT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POMGNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: POMGNT1 were set to 33528536; 17881266; 34077496
Phenotypes for gene: POMGNT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 MIM# 253280; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3 MIM#613151; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157; Retinitis pigmentosa 76 MIM#617123
Review for gene: POMGNT1 was set to GREEN
Added comment: One case report of two brothers diagnosed with CP and later found to have POMGnt1 biallelic mutations. In addition, two additional cases in two large CP cohort studies presenting with biallelic POMGnT1 mutations.
Sources: Literature
Cerebral Palsy v1.133 POGZ Luisa Weiss gene: POGZ was added
gene: POGZ was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: POGZ were set to 33528536
Phenotypes for gene: POGZ were set to White-Sutton syndrome MIM#616364
Review for gene: POGZ was set to AMBER
Added comment: 2 cases in one large cohort study, one with a likely pathogenic mutation and one with a pathogenic mutation.
Sources: Literature
Cerebral Palsy v1.133 PNPLA6 Luisa Weiss changed review comment from: 2 case reports of patients initially reported as having CP but later re-diagnosed as having spastic paraplegia Type 39 due to biallelic PNPLA6 mutations. Significant phenotypic overlap with childhood onset of sometimes very slowly progressive motor disease
Sources: Literature; to: 2 case reports of patients initially reported as having CP but later re-diagnosed as having spastic paraplegia Type 39 due to biallelic PNPLA6 mutations. Significant phenotypic overlap with HSP 39: childhood onset of potentially very slowly progressive motor disease
Sources: Literature
Cerebral Palsy v1.133 PNPLA6 Luisa Weiss gene: PNPLA6 was added
gene: PNPLA6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA6 were set to 34816117; 34364746
Phenotypes for gene: PNPLA6 were set to Boucher-Neuhauser syndrome MIM#215470; Oliver-McFarlane syndrome MIM#275400; Spastic paraplegia 39 MIM#612020
Review for gene: PNPLA6 was set to AMBER
Added comment: 2 case reports of patients initially reported as having CP but later re-diagnosed as having spastic paraplegia Type 39 due to biallelic PNPLA6 mutations. Significant phenotypic overlap with childhood onset of sometimes very slowly progressive motor disease
Sources: Literature
Cerebral Palsy v1.130 PLA2G6 Zornitza Stark Phenotypes for gene: PLA2G6 were changed from Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217; Parkinson disease 14, autosomal recessive MIM#612953 to Neurodegeneration with brain iron accumulation 2B MIM#610217
Cerebral Palsy v1.128 PIGA Zornitza Stark Phenotypes for gene: PIGA were changed from Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868; Neurodevelopmental disorder with epilepsy and hemochromatosis MIM#301072; Paroxysmal nocturnal hemoglobinuria, somatic MIM#300818 to Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868; Neurodevelopmental disorder with epilepsy and haemochromatosis MIM#301072
Cerebral Palsy v1.118 NAA10 Zornitza Stark Phenotypes for gene: NAA10 were changed from Microphthalmia, syndromic MIM#309800; Ogden syndrome MIM#300855 to Ogden syndrome MIM#300855
Cerebral Palsy v1.116 MT-TL1 Zornitza Stark Phenotypes for gene: MT-TL1 were changed from MYOCLONIC EPILEPSY ASSOCIATED WITH RAGGED-RED FIBERS MERRF MIM#545000; CYCLIC VOMITING SYNDROME WITH NEUROMUSCULAR DISEASE, INCLUDED CYCLIC VOMITING SYNDROME-PLUS, INCLUDED CVS-PLUS, INCLUDED MIM#500007; MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES MELAS MIM#540000; DIABETES AND DEAFNESS, MATERNALLY INHERITED MIDD MIM#520000 to MELAS MIM#540000
Cerebral Palsy v1.112 TUBB3 Zornitza Stark Phenotypes for gene: TUBB3 were changed from Cortical dysplasia, complex, with other brain malformations MIM#614039; Fibrosis of extraocular muscles, congenital MIM#600638 to Cortical dysplasia, complex, with other brain malformations MIM#614039
Cerebral Palsy v1.88 PMM2 Luisa Weiss gene: PMM2 was added
gene: PMM2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PMM2 were set to 34788679
Phenotypes for gene: PMM2 were set to Congenital disorder of glycosylation, type Ia MIM#212065
Review for gene: PMM2 was set to AMBER
Added comment: One patient in a large CP cohort study was found to have biallelic mutations ins PMM2, but usually PMM2-CDG presents as a progressive multisystem disease with dysmorphism.
Sources: Literature
Cerebral Palsy v1.88 PLP1 Luisa Weiss gene: PLP1 was added
gene: PLP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PLP1 were set to 33528536; 25280894; 34816117
Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher disease MIM#312080; Spastic paraplegia 2, X-linked MIM#312920
Review for gene: PLP1 was set to GREEN
Added comment: Three large cohort studies with patients initially presenting as CP found three individuals with hemizygous mutations in PLP1. Note that individuals ins PMID 33528536 and 34816117 had different base pair exchanges at the same splice site location (NM_000533:c.191+1G>T and c.191+1G>A, respectively). The other mutation was a PLP1 gene duplication. One patient also had a affected brother.
Sources: Literature
Cerebral Palsy v1.88 PLA2G6 Luisa Weiss gene: PLA2G6 was added
gene: PLA2G6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLA2G6 were set to 33528536; 34540776; 34788679
Phenotypes for gene: PLA2G6 were set to Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217; Parkinson disease 14, autosomal recessive MIM#612953
Review for gene: PLA2G6 was set to GREEN
Added comment: Three different individuals from three large CP cohort studies presenting with biallelic PLA2G6 mutations.
Sources: Literature
Cerebral Palsy v1.88 PIGA Luisa Weiss gene: PIGA was added
gene: PIGA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIGA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PIGA were set to 33528536; 24706016
Phenotypes for gene: PIGA were set to Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868; Neurodevelopmental disorder with epilepsy and hemochromatosis MIM#301072; Paroxysmal nocturnal hemoglobinuria, somatic MIM#300818
Review for gene: PIGA was set to GREEN
Added comment: One case in a large CP cohort study with maternally inherited PIGA mutation predicted to be likely pathogenic.
In addition, Kato (PMID 24706016) reviewed 7 cases of boys with hemizygous PIGA mutations and encephalopathies, two of which had non-progressive hypotonic quadriplegia and one had spastic quadriplegia. They also showed intellectual disability and seizures. No CP diagnoses was given, but phenotypic overlap is present.
Sources: Literature
Cerebral Palsy v1.88 PDHX Luisa Weiss gene: PDHX was added
gene: PDHX was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PDHX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDHX were set to 33528536; 35076175; 34540776
Phenotypes for gene: PDHX were set to Lacticacidemia due to PDX1 deficiency MIM#245349
Review for gene: PDHX was set to GREEN
Added comment: Three individual patients from three large CP cohort studies with homozygous PDHX mutations. Note that in one case (PMID 35076175) the patient had both homozygous PDHX and homozygous ACADM mutations, but his phenotype was more consistent with PDHX mutations.
Sources: Literature
Cerebral Palsy v1.88 PDHA1 Luisa Weiss gene: PDHA1 was added
gene: PDHA1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PDHA1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: PDHA1 were set to 33528536; 10486093
Phenotypes for gene: PDHA1 were set to Pyruvate dehydrogenase E1-alpha deficiency MIM#312170
Review for gene: PDHA1 was set to GREEN
Added comment: 2 patients in 1 large CP cohort presented with heterozygous likely pathogenic missense mutations, one of them confirmed de novo.
In an older case report (PMID:10486093) two unrelated girls were presented with cerebral palsy which were found to harbor heterozygous PDHA mutations. In one case, parental DNA wasn't analyzed, in the other case the mutation wasn't found in the healthy mother and the healthy brother of the patient. Both girls showed skewed X-Inactivation.
Note that in X-linked PDH deficiency it has been shown that a high proportion of heterozygous females manifest severe symptoms.
Sources: Literature
Cerebral Palsy v1.88 PANK2 Luisa Weiss reviewed gene: PANK2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33098801, 34114234, 25131622; Phenotypes: HARP syndrome MIM#607236, Neurodegeneration with brain iron accumulation MIM#234200; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.88 PAK3 Luisa Weiss reviewed gene: PAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31444167, 30542205, 25666757; Phenotypes: Intellectual developmental disorder, X-linked MIM#300558; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.88 PAFAH1B1 Luisa Weiss gene: PAFAH1B1 was added
gene: PAFAH1B1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PAFAH1B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PAFAH1B1 were set to 19667223
Phenotypes for gene: PAFAH1B1 were set to Lissencephaly MIM#607432; Subcortical laminar heterotopia MIM#607432
Review for gene: PAFAH1B1 was set to GREEN
Added comment: Saillour reviewed 63 patients with posteriorly predominant lissencephaly, 40 of which were proven to have a LIS1 mutation. None of them were officially diagnosed with cerebral palsy, however, 24 of those 40 patients presented with "severe motor impairment including axial hypotonia and spastic quadriparesis". A high percentage of patients also showed severe developmental delay and epilepsy.
Sources: Literature
Cerebral Palsy v1.88 NFIX Luisa Weiss gene: NFIX was added
gene: NFIX was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NFIX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NFIX were set to 34788679
Phenotypes for gene: NFIX were set to Malan syndrome MIM#614753; Marshall-Smith syndrome MIM#602535
Review for gene: NFIX was set to AMBER
Added comment: Two patients in a large CP cohort study, one with a nonsense mutation without information on inheritance and one with a de novo missense mutation predicted to be likely pathogenic. Normally, NFIX mutation cause accelerated bone maturation with overgrwowth, dysmorphism and mental retardation, so there is a low possibility for phenotypic overlap.
Sources: Literature
Cerebral Palsy v1.88 NAA10 Luisa Weiss gene: NAA10 was added
gene: NAA10 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NAA10 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: NAA10 were set to 33528536; 30542205
Phenotypes for gene: NAA10 were set to Microphthalmia, syndromic MIM#309800; Ogden syndrome MIM#300855
Review for gene: NAA10 was set to GREEN
Added comment: Four individual cases in two large CP cohort studies. Note that in one publication (33528536) 2/3 mutations occurred de novo.
Sources: Literature
Cerebral Palsy v1.88 MT-TL1 Luisa Weiss gene: MT-TL1 was added
gene: MT-TL1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene gene: MT-TL1 was set to MITOCHONDRIAL
Publications for gene: MT-TL1 were set to 34531397; 34077496; 25280894
Phenotypes for gene: MT-TL1 were set to MYOCLONIC EPILEPSY ASSOCIATED WITH RAGGED-RED FIBERS MERRF MIM#545000; CYCLIC VOMITING SYNDROME WITH NEUROMUSCULAR DISEASE, INCLUDED CYCLIC VOMITING SYNDROME-PLUS, INCLUDED CVS-PLUS, INCLUDED MIM#500007; MITOCHONDRIAL MYOPATHY, ENCEPHALOPATHY, LACTIC ACIDOSIS, AND STROKE-LIKE EPISODES MELAS MIM#540000; DIABETES AND DEAFNESS, MATERNALLY INHERITED MIDD MIM#520000
Review for gene: MT-TL1 was set to GREEN
Added comment: Three individual cases in three different large CP cohort publications. In one case, heteroplasmy was 8% in another it was 58% with a low level detectable also in the mother. The third does not state the heteroplasmy level. Note very high intra- and interfamilial variability, partly due to heteroplasmy level in different tissues.
Sources: Literature
Cerebral Palsy v1.88 TUBB2A Luisa Weiss gene: TUBB2A was added
gene: TUBB2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBB2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB2A were set to 33528536; 24702957
Phenotypes for gene: TUBB2A were set to Cortical dysplasia, complex, with other brain malformations MIM# 615763
Review for gene: TUBB2A was set to GREEN
Added comment: 4 individual cases in one large CP cohort study, all of them with de novo missense mutations, Note that 2/4 mutations are p.A248V, which has also been described in a nonverbal and nonambulatory girl with generalized hypotonia and mild brain malformations (dysmorphic corpus callosum). Cushion et al. (PMID 24702957) also did functional work on this variant showing is had an impaired ability to coassemble with endogenous alpha-tubulin subunits and integrate into microtubule polymers.
Sources: Literature
Cerebral Palsy v1.88 TUBB3 Luisa Weiss gene: TUBB3 was added
gene: TUBB3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB3 were set to 33528536
Phenotypes for gene: TUBB3 were set to Cortical dysplasia, complex, with other brain malformations MIM#614039; Fibrosis of extraocular muscles, congenital MIM#600638
Review for gene: TUBB3 was set to GREEN
Added comment: 4 individual cases in one large CP cohort study, all with de novo missense mutations predicted to be pathogenic.
Sources: Literature
Cerebral Palsy v1.88 MSL3 Luisa Weiss gene: MSL3 was added
gene: MSL3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MSL3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: MSL3 were set to 33173220
Phenotypes for gene: MSL3 were set to Basilicata-Akhtar syndrome MIM#301032
Review for gene: MSL3 was set to GREEN
Added comment: Brunet et al. defined the clinical phenotype of 25 patients with MSL3 mutations, three of which had initially been diagnosed as having cerebral palsy.
Sources: Literature
Cerebral Palsy v1.88 MOCS2 Luisa Weiss gene: MOCS2 was added
gene: MOCS2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MOCS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOCS2 were set to 33528536; 22759696
Phenotypes for gene: MOCS2 were set to Molybdenum cofactor deficiency B MIM#252160
Review for gene: MOCS2 was set to GREEN
Added comment: Two patients in a large CP cohort presenting with cerebral palsy. In addition one case report with a patient initially diagnosed as having CP and later found to have biallelic MOCS2 mutations.
Sources: Literature
Cerebral Palsy v1.88 MOCS1 Luisa Weiss reviewed gene: MOCS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 34788679, 27289259; Phenotypes: Molybdenum cofactor deficiency A MIM#252150; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.88 MOCS1 Luisa Weiss Deleted their review
Cerebral Palsy v1.88 MEF2C Luisa Weiss gene: MEF2C was added
gene: MEF2C was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MEF2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MEF2C were set to 20412115; 25817843; 33528536
Phenotypes for gene: MEF2C were set to Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language MIM#613443
Review for gene: MEF2C was set to GREEN
Added comment: Two patients in two large CP cohort studies with MEF2C mutations/deletions. In addition, one case report of two patients with MEF2C mutation with one of them diagnosed as having CP.
Sources: Literature
Cerebral Palsy v1.88 MOCS1 Luisa Weiss gene: MOCS1 was added
gene: MOCS1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MOCS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MOCS1 were set to 22759696; 34788679
Phenotypes for gene: MOCS1 were set to Molybdenum cofactor deficiency A MIM#252150
Review for gene: MOCS1 was set to AMBER
Added comment: One patient described in a case report diagnosed with cerebral palsy and later re-diagnosed as having molybdenum cofactor deficiency. In addition one more patient in a large CP cohort with biallelic MOCS1 mutation.
Sources: Literature
Cerebral Palsy v1.88 MCOLN1 Luisa Weiss gene: MCOLN1 was added
gene: MCOLN1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MCOLN1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCOLN1 were set to 12182165; 21763169
Phenotypes for gene: MCOLN1 were set to Mucolipidosis IV MIM#252650
Review for gene: MCOLN1 was set to GREEN
Added comment: PMID 12182165 presents a case study of 28 patients with Mucolipidosis Type IV. A significant clinical overlap with CP-like encephalopathy is discussed and some of the patients are reported to present with a 'pure non-progressive neurologic deficit'. Other Mucolipidosis Type IV overviews (PMID 21763169) also discuss the clinical similarities and the phenotypic overlap between MLIV and CP.
Sources: Literature
Cerebral Palsy v1.88 MAST1 Luisa Weiss gene: MAST1 was added
gene: MAST1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAST1 were set to 31700678; 25666757
Phenotypes for gene: MAST1 were set to Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations MIM#618273
Review for gene: MAST1 was set to AMBER
Added comment: Two large CP cohorts, one with one likely pathogenic de novo mutation and two VUS, one of them inherited paternally. The other cohort showed one more case with a de novo missense mutation predicted to be pathogenic. Note that no information is given on the MRI phenotype in these cohorts, so it might be a phenotypic overlap with MIM#618273.
Sources: Literature
Cerebral Palsy v1.88 MLC1 Luisa Weiss gene: MLC1 was added
gene: MLC1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MLC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MLC1 were set to 34788679
Phenotypes for gene: MLC1 were set to Megalencephalic leukoencephalopathy with subcortical cysts MIM#604004
Review for gene: MLC1 was set to AMBER
Added comment: One patient in a larger CP cohort harbouring compound heterozygous MLC1 mutations. Phenotypic overlap between MIM#604004 and CP, however, seems small, as MIM#604004 is a progressive neurological disorder with MRI abnormalities.
Sources: Literature
Cerebral Palsy v1.88 MFN2 Luisa Weiss reviewed gene: MFN2: Rating: AMBER; Mode of pathogenicity: None; Publications: 33528536, 34114234, 34531397; Phenotypes: Charcot-Marie-Tooth disease, axonal, type 2A2A MIM#609260, Hereditary motor and sensory neuropathy VIA MIM#601152; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.86 TUBB2B Luisa Weiss reviewed gene: TUBB2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 34077496; Phenotypes: Cortical dysplasia, complex, with other brain malformations MIM#610031; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.86 WDR26 Luisa Weiss gene: WDR26 was added
gene: WDR26 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: WDR26 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: WDR26 were set to 33528536; 34788679
Phenotypes for gene: WDR26 were set to Skraban-Deardorff syndrome MIM#617616
Review for gene: WDR26 was set to GREEN
Added comment: Two large CP cohort studies with 3 individual patients harbouring de novo missense or nonsense mutations or whole gene deletions in WDR26.
Sources: Literature
Cerebral Palsy v1.86 WWOX Luisa Weiss gene: WWOX was added
gene: WWOX was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: WWOX was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WWOX were set to 34540776; 30361190; 33528536
Phenotypes for gene: WWOX were set to Developmental and epileptic encephalopathy MIM#616211; Spinocerebellar ataxia MIM#6143223
Review for gene: WWOX was set to GREEN
Added comment: 2 large CP cohort studies with 4 patients in total harbouring a biallelic WWOX mutation. In addition, case reports of patients with epileptic encephalopathy due to WWOX mutations show significant phenotypic overlap with CP
Sources: Literature
Cerebral Palsy v1.86 MAP2K1 Luisa Weiss edited their review of gene: MAP2K1: Changed rating: GREEN
Cerebral Palsy v1.86 MAP2K1 Luisa Weiss gene: MAP2K1 was added
gene: MAP2K1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MAP2K1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAP2K1 were set to 33528536
Phenotypes for gene: MAP2K1 were set to Cardiofaciocutaneous syndrome MIM#615279
Added comment: Four individual cases in one large CP cohort study. All of them missense and confirmed de novo. Note that the c.A389G,p.Y130C mutation affected 3/4 patients and seems to be a recurrent mutation. This mutation has also been described in patients with cardiofaciocutanuous syndrome.
Sources: Literature
Cerebral Palsy v1.86 KMT2B Luisa Weiss reviewed gene: KMT2B: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 25666757; Phenotypes: Dystonia 28, childhood-onset MIM#617284, Intellectual developmental disorder, autosomal dominant MIM#619934; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.86 KCNT1 Luisa Weiss gene: KCNT1 was added
gene: KCNT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNT1 were set to 33528536; 34788679
Phenotypes for gene: KCNT1 were set to Developmental and epileptic encephalopathy MIM#614959
Review for gene: KCNT1 was set to GREEN
Added comment: 4 cases in two large CP cohort studies. All of them are missense mutations, mostly confirmed de novo mutations.
Sources: Literature
Cerebral Palsy v1.86 KCNB1 Luisa Weiss gene: KCNB1 was added
gene: KCNB1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KCNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNB1 were set to 33528536; 34788679
Phenotypes for gene: KCNB1 were set to Developmental and epileptic encephalopathy MIM#616056
Review for gene: KCNB1 was set to AMBER
Added comment: One case each in two large CP cohort studies with heterozygous missense mutations, only one of the mutations confirmed de novo.
Sources: Literature
Cerebral Palsy v1.86 KAT6A Luisa Weiss gene: KAT6A was added
gene: KAT6A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KAT6A were set to 33528536
Phenotypes for gene: KAT6A were set to Arboleda-Tham syndrome MIM#616268
Review for gene: KAT6A was set to GREEN
Added comment: Several cases in a large CP cohort study with Loss of function mutations in KAT6A, all mutations confrimed de novo
Sources: Literature
Cerebral Palsy v1.86 IRF2BPL Luisa Weiss gene: IRF2BPL was added
gene: IRF2BPL was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF2BPL were set to 30057031; 30166628
Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures MIM#618088
Review for gene: IRF2BPL was set to GREEN
Added comment: Two large IRF2BPL cohort studies, in one study (PMID:30166628) two children had previously been described with different forms of CP and later found to have a frameshift IRF2BPL mutation. In the other publication (PMID:3005703) there was significant phenotypic overlap with spasticity and non-progressive movemetn disorder, even though no formal CP diagnosis had been made.
Sources: Literature
Cerebral Palsy v1.86 IQSEC2 Luisa Weiss reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536; Phenotypes: Intellectual developmental disorder MIM#09530; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v1.86 IFIH1 Luisa Weiss gene: IFIH1 was added
gene: IFIH1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: IFIH1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IFIH1 were set to 34788679; 33177673; 33528536
Phenotypes for gene: IFIH1 were set to Aicardi-Goutieres syndrome 7 MIM#615846; Immunodeficiency 95 MIM#619773; Singleton-Merten syndrome MIM#182250
Review for gene: IFIH1 was set to GREEN
Added comment: Three large CP cohort publication with one patient each presenting with CP and harbouring a IFIH1 mutation (missense mutations). Note that the gene can have a very variable phenotype and incomplete penetrance has been reported for other diseases associated with mutatons in this gene.
Sources: Literature
Cerebral Palsy v1.86 HUWE1 Luisa Weiss gene: HUWE1 was added
gene: HUWE1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HUWE1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: HUWE1 were set to 31700678
Phenotypes for gene: HUWE1 were set to Intellectual developmental disorder, X-linked syndromic, Turner type MIM#309590
Review for gene: HUWE1 was set to AMBER
Added comment: 1 large CP cohort study with three cases of HUWE1 mutation, two of which are VUS and one a likely benign variant. Note that one of the VUS is paternally inherited. No certain phenotypic overlap as HUWE1 mutations tend to cause ID, sometimes with muscular hypotonia.
Sources: Literature
Cerebral Palsy v1.86 HPRT1 Luisa Weiss gene: HPRT1 was added
gene: HPRT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HPRT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: HPRT1 were set to 34788679, 30799092
Phenotypes for gene: HPRT1 were set to Hyperuricemia, HRPT-related MIM#300323; Lesch-Nyhan syndrome MIM#300322
Review for gene: HPRT1 was set to GREEN
Added comment: Several (>3) cases in large CP cohort studies present with different forms of CP.
Sources: Literature
Cerebral Palsy v1.86 HPDL Luisa Weiss reviewed gene: HPDL: Rating: GREEN; Mode of pathogenicity: None; Publications: 33634263, 32707086; Phenotypes: Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities MIM#619026; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.86 GRIN1 Luisa Weiss gene: GRIN1 was added
gene: GRIN1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GRIN1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GRIN1 were set to 33528536; 34788679
Phenotypes for gene: GRIN1 were set to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant MIM#614254 AD
Review for gene: GRIN1 was set to GREEN
Added comment: 3 individuals in a large CP cohort study with heterozygous mutations in GRIN1, two of which reported to be de novo. Another single patient in a large cohort study with heterozygous de novo mutation. All of these mutations are missense mutations. Note that there are other disorders associated with this gene that are due to biallelic mutations in GRIN1, however, for CP only heterozygous mutations are described so far.
Sources: Literature
Cerebral Palsy v1.86 GCDH Luisa Weiss Deleted their comment
Cerebral Palsy v1.86 GCDH Luisa Weiss edited their review of gene: GCDH: Added comment: One larger cohort study on 34 patients with Glutaric Aciduria Type 1 (GA1) that showed that patient diagnosed clinically will develop a CP at school age in 64% (7 out of 11 cases).
In addition, there are several case reports of patients with dystonic, dyskinetic or spastic CP that were diagnosed with biallelic mutations in GCDH and biochemically corresponding features. Also, one case in a larger cohort study of patients with atypical CP (no mutation information given for this patient).; Changed rating: GREEN; Changed publications: 30542205, 26593172, 25280894, 30271473, 35822093
Cerebral Palsy v1.86 COL4A1 Luisa Weiss changed review comment from: More than 8 individuals reported with heterozygous mutations in COL4A2 and CP in large cohort studies. Note that some of these mutations have been inherited from one parent so incomplete penetrance is likely. In one study, it is hypothesized that COL4A2 mutations can cause vascular instability and might thus pose a risk for perinatal intracranial hemorrhage resulting in CP.; to: More than 8 individuals reported with heterozygous mutations in COL4A1 and CP in large cohort studies. Note that some of these mutations have been inherited from one parent so incomplete penetrance is likely. In one study, it is hypothesized that COL4A1 mutations can cause vascular instability and might thus pose a risk for perinatal intracranial hemorrhage resulting in CP.
Cerebral Palsy v1.85 ACTB Zornitza Stark Mode of inheritance for gene: ACTB was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.78 AKT3 Zornitza Stark reviewed gene: AKT3: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 2, MIM# 615937; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.71 CACNA1A Zornitza Stark Phenotypes for gene: CACNA1A were changed from Developemental and epileptic encephalopathy 42, MIM# 617106; Episodic ataxia, type 2, MIM# 108500; Migraine, familial hemiplegic, 1, MIM# 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia 141500; Spinocerebellar ataxia 6, MIM# 183086 to Developemental and epileptic encephalopathy 42, MIM# 617106; Episodic ataxia, type 2, MIM# 108500; Spinocerebellar ataxia 6, MIM# 183086
Cerebral Palsy v1.67 CDKL5 Zornitza Stark Phenotypes for gene: CDKL5 were changed from to Developmental and epileptic encephalopathy 2, MIM# 300672
Cerebral Palsy v1.54 DYNC1H1 Zornitza Stark Phenotypes for gene: DYNC1H1 were changed from Charcot-Marie-Tooth disease MIM#614228; Cortical dysplasia, complex MIM#614563; Spinal muscular atrophy, lower extremity-predominant MIM#158600 to Cortical dysplasia, complex MIM#614563
Cerebral Palsy v1.40 FLNA Zornitza Stark reviewed gene: FLNA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Heterotopia, periventricular, 1, MIM#300049; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v1.39 FRRS1L Zornitza Stark reviewed gene: FRRS1L: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy MIM#616981; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.36 GCDH Luisa Weiss gene: GCDH was added
gene: GCDH was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GCDH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: GCDH were set to 30542205; 26593172
Phenotypes for gene: GCDH were set to Glutaricaciduria, type I MIM#231670
Review for gene: GCDH was set to AMBER
Added comment: One case in a larger cohort study of patients with atypical CP, no mutation information given. One case report of one boy diagnosed with dystonic CP and homozygous missense mutation in GCDH with biochemically corresponding features.
Sources: Literature
Cerebral Palsy v1.36 GABRB2 Luisa Weiss gene: GABRB2 was added
gene: GABRB2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GABRB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB2 were set to 33528536
Phenotypes for gene: GABRB2 were set to Developmental and epileptic encephalopathy MIM#617829
Review for gene: GABRB2 was set to AMBER
Added comment: Two cases in a large CP cohort study with heterozygous de novo mutations in GABRB2.
Sources: Literature
Cerebral Palsy v1.36 GABRB1 Luisa Weiss gene: GABRB1 was added
gene: GABRB1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: GABRB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GABRB1 were set to 34540776
Phenotypes for gene: GABRB1 were set to Developmental and epileptic encephalopathy MIM#617153
Review for gene: GABRB1 was set to RED
Added comment: One large cohort study on CP patients from Iran presents one patient with a heterozygous mutation in GABRB1 and atypical CP with developmental delay, ID and microcephaly. The patient's mutation (NM_000812:c.1243G>C,p.G415R) is present in a heterozygous state in the patient and no information about inheritance is given. The authors propose a recessively inherited disease. The variant is classified as a variant of unknown significance in this paper.
Sources: Literature
Cerebral Palsy v1.36 FRRS1L Luisa Weiss gene: FRRS1L was added
gene: FRRS1L was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FRRS1L was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRRS1L were set to 33528536; 27236917
Phenotypes for gene: FRRS1L were set to Developmental and epileptic encephalopathy MIM#616981
Review for gene: FRRS1L was set to GREEN
Added comment: Three independent patients in a large CP cohort study with the same recurrent homozygous mutation (NM_014334:c.735_737del,p.245_246del).
Another cohort study of multiple patients with biallelic FRRS1L mutations and epileptic-dyskinetic encephalopathy described on patient (individual 4_II-1) with non-progressive movement disorder in addition to epilepsy.
Sources: Literature
Cerebral Palsy v1.36 FLNA Luisa Weiss gene: FLNA was added
gene: FLNA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: FLNA were set to 29706646; 34077496; 25817843
Phenotypes for gene: FLNA were set to Cardiac valvular dysplasia MIM#314400; Congenital short bowel syndrome MIM#300048; Frontometaphyseal dysplasia MIM#305620; Heterotopia, periventricular MIM#300049; Intestinal pseudoobstruction MIM#300048; Melnick-Needles syndrome MIM#309350; Otopalatodigital syndrome I MIM#311300; Otopalatodigital syndrome II MIM# 304120; Terminal osseous dysplasia MIM#300244
Review for gene: FLNA was set to GREEN
Added comment: In a large Chinese cohort study two male patients with hemizygous FLNA missense mutations and spastic hemiplegic CP were identified. One additional patient in a cohort study of 52 patients with CP investigated for causative CNVs. This patient harbored a pathogenic maternally inherited triplication on Xq28 including FLNA. No information about the patient's gender is given.
One other cohort study (PMID 29706646) of patients with cortical malformations, which can be associated with CP overlapping features, also revealed one female patient with maternally inherited heterozygous FLNA mutation and ataxia. The mother had the same neuroradiologic features but did not show any symptoms.
Sources: Literature
Cerebral Palsy v1.36 FH Luisa Weiss gene: FH was added
gene: FH was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FH was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FH were set to 33528536; 27541980; 1432428
Phenotypes for gene: FH were set to Fumarase deficiency MIM#606812
Review for gene: FH was set to GREEN
Added comment: Two patients from a large CP cohort with biallelic (compound heterozygous) mutations in FH. Note that there is a recurrent mutation (NM_000143:c.1429_1430insAAA,p.K477delinsKK) which was already described in a compound heterozygous state in two sister with an attenuated form of fumarase deficiency and slowly progressive movement disorder (PMID:27541980).
One other case report of a girl with a previous diagnosis of cerebral palsy, nonprogressive
psychomotor retardation, and hypotonia and reduced fibroblast activity of FH to 10% and parental fibroblast activity of FH in the heterozygote range. No genetic testing had been performed on this patient.
Sources: Literature
Cerebral Palsy v1.36 ATM Luisa Weiss changed review comment from: 3 individuals presenting with CP and harboring biallelic compound heterozygous mutations in ATM. At least one the individual had an overlapping phenotype of CP with Ataxia Teleangiectasia
Sources: Literature; to: 3 individuals presenting with CP and harboring biallelic compound heterozygous mutations in ATM. At least one of the individual had an overlapping phenotype of CP with Ataxia Teleangiectasia
Sources: Literature
Cerebral Palsy v1.36 FARS2 Luisa Weiss gene: FARS2 was added
gene: FARS2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FARS2 were set to 33528536; 32989326; 25851414
Phenotypes for gene: FARS2 were set to Combined oxidative phosphorylation deficiency MIM#614946; 3 Spastic paraplegia MIM#617046
Review for gene: FARS2 was set to GREEN
Added comment: Four patients out of three publications (two large CP cohort studies with one patient each, one case report of two sibling with the clinical diagnosis of CP) with biallelic mutations in FARS2.
Sources: Literature
Cerebral Palsy v1.36 FAR1 Luisa Weiss gene: FAR1 was added
gene: FAR1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FAR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FAR1 were set to 33239752
Phenotypes for gene: FAR1 were set to Cataracts, spastic paraparesis, and speech delay MIM#619338
Mode of pathogenicity for gene: FAR1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: FAR1 was set to GREEN
Added comment: One publication with a total of 12 patients with an amino acid change at position 480 (p.Arg480Cys/His/Leu) of FAR1 and movement disorder, epilepsy and cataract. The movement disorder was non-progressive in almost all of the individuals even though the clinical diagnosis of CP was not given.
Functional studies in the same publication showed that patients with the heterozygous de novo variants have elevated levels of ether lipids, including plasmalogens, which makes these mutations gain-of-function mutations (in contrast to the peroxisomal fatty acyl-CoA reductase 1 disorder, which is caused by biallelic loss-of-function mutations in the same gene).
Sources: Literature
Cerebral Palsy v1.36 EEF1A2 Luisa Weiss gene: EEF1A2 was added
gene: EEF1A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EEF1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EEF1A2 were set to 33528536; 30109124; 32196822
Phenotypes for gene: EEF1A2 were set to Developmental and epileptic encephalopathy MIM#616409
Review for gene: EEF1A2 was set to AMBER
Added comment: One patient in a large CP cohort with heterozygous EEF1A2 mutation. In another publication there is one patient from a cohort of patients with EIEE and EEF1A2 mutations that was also reported to have CP.
One other paper (PMID:32196822) presents a cohort of patients with epileptic-dyskinetic encephalopathy due to heterozygous de novo EEIF1A2 mutations of which 4 had a non-progressive movement disorder without the clinical diagnosis of CP.
Sources: Literature
Cerebral Palsy v1.36 ELP2 Luisa Weiss changed review comment from: Nine patients in two different publications described as having biallelic ELP2 mutations and a form of ID syndrome with cerebral palsy as one neurological feature. At least for one patient symptom progression was described.
Sources: Literature; to: Nine patients in two different publications described as having biallelic ELP2 mutations and a form of ID syndrome with cerebral palsy as one neurological feature. For one patient symptom progression was described.
Sources: Literature
Cerebral Palsy v1.36 ERCC8 Luisa Weiss changed review comment from: One large CP cohort study with 3 unrelated patients with biallelic mutations in ERCC8. Two were point mutations (one missense, one nonsense), the other a large deletion that included ERCC8 and NDUFAF2-gene. Another case report of a boy that was initially diagnosed as having CP but later re-diagnosed as having Cockayne syndrome due to biallelic ERCC8 mutations.
Sources: Literature; to: One large CP cohort study with 3 unrelated patients with biallelic mutations in ERCC8. Two were point mutations (one missense, one nonsense), the other a large deletion that included ERCC8 and NDUFAF2-gene. Another case report of a boy that was initially diagnosed as having CP but later re-diagnosed as having Cockayne syndrome due to biallelic ERCC8 mutations because of disease progression.
Sources: Literature
Cerebral Palsy v1.36 FAM126A Luisa Weiss gene: FAM126A was added
gene: FAM126A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FAM126A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAM126A were set to 34788679
Phenotypes for gene: FAM126A were set to Leukodystrophy, hypomyelinating MIM#610532
Review for gene: FAM126A was set to AMBER
Added comment: One large CP cohort study with one patient with a homozygous HYCC1/FAM126A mutation and CP
Sources: Literature
Cerebral Palsy v1.36 EXOSC3 Luisa Weiss gene: EXOSC3 was added
gene: EXOSC3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: EXOSC3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EXOSC3 were set to 33528536
Phenotypes for gene: EXOSC3 were set to Pontocerebellar hypoplasia MIM#614678
Review for gene: EXOSC3 was set to GREEN
Added comment: One large CP cohort study with 3 unrelated patients harboring the same homozygous missense mutation (p.D132A). The same missense mutation has been described in a homozygous state as well as compound heterozygous with a different pathogenic mutation in the same gene as causing pontocerebellar hypoplasia.
Sources: Literature
Cerebral Palsy v1.36 ERCC8 Luisa Weiss gene: ERCC8 was added
gene: ERCC8 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ERCC8 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERCC8 were set to 33528536; 30279719
Phenotypes for gene: ERCC8 were set to Cockayne syndrome MIM#216400
Review for gene: ERCC8 was set to GREEN
Added comment: One large CP cohort study with 3 unrelated patients with biallelic mutations in ERCC8. Two were point mutations (one missense, one nonsense), the other a large deletion that included ERCC8 and NDUFAF2-gene. Another case report of a boy that was initially diagnosed as having CP but later re-diagnosed as having Cockayne syndrome due to biallelic ERCC8 mutations.
Sources: Literature
Cerebral Palsy v1.36 ELP2 Luisa Weiss gene: ELP2 was added
gene: ELP2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ELP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ELP2 were set to 25131622; 33976153
Phenotypes for gene: ELP2 were set to Intellectual developmental disorder MIM#617270
Review for gene: ELP2 was set to GREEN
Added comment: Nine patients in two different publications described as having biallelic ELP2 mutations and a form of ID syndrome with cerebral palsy as one neurological feature. At least for one patient symptom progression was described.
Sources: Literature
Cerebral Palsy v1.36 DYRK1A Luisa Weiss gene: DYRK1A was added
gene: DYRK1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DYRK1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYRK1A were set to 33528536
Phenotypes for gene: DYRK1A were set to Intellectual developmental disorder MIM#614104
Review for gene: DYRK1A was set to GREEN
Added comment: 6 patients in one large CP cohort study described with mutations in DYRK1A.
Sources: Literature
Cerebral Palsy v1.36 DYNC1H1 Luisa Weiss gene: DYNC1H1 was added
gene: DYNC1H1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DYNC1H1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DYNC1H1 were set to 33528536; 25817843
Phenotypes for gene: DYNC1H1 were set to Charcot-Marie-Tooth disease MIM#614228; Cortical dysplasia, complex MIM#614563; Spinal muscular atrophy, lower extremity-predominant MIM#158600
Review for gene: DYNC1H1 was set to GREEN
Added comment: Four patients with de novo heterozygous missense mutations and one patient with a de novo gene deletion in DYNC1H1 in two independent CP cohort studies described.
Sources: Literature
Cerebral Palsy v1.36 DOCK6 Luisa Weiss gene: DOCK6 was added
gene: DOCK6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DOCK6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DOCK6 were set to 25824905; 34114234
Phenotypes for gene: DOCK6 were set to Adams-Oliver syndrome 2 MIM#614219
Review for gene: DOCK6 was set to GREEN
Added comment: In one study (PMID:25824905) ten patients with Adams-Oliver syndrome type 2 were described, 4 of which had CP. All of them had ocular anomalies and scalp defects, indicating that there is a high phenotypic overlap with the autosomal recessive form of Adams-Oliver-syndrome that is associated with eye anomalies.
In another CP cohort study (PMID: 34114234) one patient with biallelic variants of unknown clinical significance in DOCK6 was described, but there was no indication of eye or skin anomalies.
Sources: Literature
Cerebral Palsy v1.36 CTNNA2 Luisa Weiss gene: CTNNA2 was added
gene: CTNNA2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CTNNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CTNNA2 were set to 30013181
Phenotypes for gene: CTNNA2 were set to Cortical dysplasia, complex, with other brain malformations MIM#618174
Review for gene: CTNNA2 was set to GREEN
Added comment: In 7 affected individuals of three consanguineous families a complex brain malformation syndrome with pachygyria, cortical gray matter thickening, hypogenesis of the corpus callosum, and cerebellar hypoplasia, neurodevelopmental delay, acquired microcephaly and seizures is described. All of the individuals are described as having hypotonic cerebral palsy and biallelic mutations in CTNNA2.
Sources: Literature
Cerebral Palsy v1.36 CTBP1 Luisa Weiss gene: CTBP1 was added
gene: CTBP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CTBP1 were set to 33528536
Phenotypes for gene: CTBP1 were set to Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome MIM#617915
Review for gene: CTBP1 was set to AMBER
Added comment: Two independent patients in one large CP cohort studies with the same mutations in this gene (p.R342W), both heterozygous, one of them confirmed de novo.

Another recurrent, possibly dominant negative functioning mutation described as causing an ID syndrome with ataxia, hypotonia and tooth enamel defects. Since there is no phenotype given in the CP cohort study, a possible phenotypic overlap cannot be ruled out.
Sources: Literature
Cerebral Palsy v1.36 CREBBP Luisa Weiss gene: CREBBP was added
gene: CREBBP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CREBBP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CREBBP were set to 33528536; 34788679
Phenotypes for gene: CREBBP were set to Menke-Hennekam syndrome MIM#618332, Rubinstein-Taybi syndrome MIM#180849
Review for gene: CREBBP was set to GREEN
Added comment: 3 independent patients in 2 large CP cohort studies describes as having heterozygous de novo mutations in this gene. One mutation (PMID: 34788679) is a frameshift mutation, the two other mutations (PMID: 33528536) are missense mutations, one of which (p.M1872V) was already described twice in patients with Menke-Hennekam syndrome. Possible phenotypic overlap with ID syndrome.
Sources: Literature
Cerebral Palsy v1.36 COL4A1 Luisa Weiss reviewed gene: COL4A1: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 34531397; Phenotypes: Brain small vessel disease MIM#614483; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.36 CLTC Luisa Weiss gene: CLTC was added
gene: CLTC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CLTC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CLTC were set to 33528536; 31776469
Phenotypes for gene: CLTC were set to Intellectual developmental disorder MIM#617854
Review for gene: CLTC was set to GREEN
Added comment: One large CP cohort study with one patient reported.

One more publication with 13 cases of syndromic ID due to heterozygous CLTC mutations. Cerebral palsy affecting gait recurrently seen in these individuals.
Sources: Literature
Cerebral Palsy v1.36 CLCN4 Luisa Weiss gene: CLCN4 was added
gene: CLCN4 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CLCN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: CLCN4 were set to 34788679
Phenotypes for gene: CLCN4 were set to Raynaud-Claes syndrome MIM#300114
Review for gene: CLCN4 was set to AMBER
Added comment: One female patient presented in a large cohort study with phenotypic overlap to Raynaud-Claes syndrome (ID, epilepsy and language deficits). The mutation is a heterozygous missense mutation previously reported to cause Raynaud-Claes syndrome.
Sources: Literature
Cerebral Palsy v1.36 ATP7B Luisa Weiss gene: ATP7B was added
gene: ATP7B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATP7B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP7B were set to 34788679
Phenotypes for gene: ATP7B were set to Wilson disease MIM#277900
Review for gene: ATP7B was set to RED
Added comment: One reported case in a large CP cohort study with two mutations in ATP7B, however bi-parental inheritance was not confirmed. Low evidence for causality.
Sources: Literature
Cerebral Palsy v1.36 CHD8 Luisa Weiss gene: CHD8 was added
gene: CHD8 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CHD8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CHD8 were set to 33528536
Phenotypes for gene: CHD8 were set to Intellectual developmental disorder with autism and macrocephaly #615032
Review for gene: CHD8 was set to GREEN
Added comment: 3 individual cases in one large cohort study, two de novo missense mutations and one frameshift mutation with unknown inheritance.
Sources: Literature
Cerebral Palsy v1.36 CDKL5 Luisa Weiss gene: CDKL5 was added
gene: CDKL5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CDKL5 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: CDKL5 were set to 33528536; 34788679
Review for gene: CDKL5 was set to AMBER
Added comment: 2 individual cases in two independent large cohort studies. One mutation reported as a mosaic nonsense mutation, the other one reported as a de novo hemizygous frameshift mutation. No phenotype information given.
Sources: Literature
Cerebral Palsy v1.36 CASK Luisa Weiss gene: CASK was added
gene: CASK was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: CASK was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: CASK were set to 33528536
Phenotypes for gene: CASK were set to Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749
Review for gene: CASK was set to GREEN
Added comment: 4 individual cases in one large CP cohort study. 3 of them confirmed de novo nonsense mutations, one in-frame five AA deletion with unknown inheritance. All reported to be heterozygous in an X-linked gene and thus affecting females as known for the allelic disease ID with pontine and cerebellar hypoplasia.
Sources: Literature
Cerebral Palsy v1.36 CACNA1A Luisa Weiss reviewed gene: CACNA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 29761117, 33528536, 34364746, 34531397, 34788679; Phenotypes: Developmental and epileptic encephalopathy MIM#617106, Episodic ataxia MIM#108500, familial hemiplegic Migraine MIM#141500 and MIM#141500, Spinocerebellar ataxia MIM#183086; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.36 BRAT1 Luisa Weiss gene: BRAT1 was added
gene: BRAT1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: BRAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: BRAT1 were set to 29997391
Phenotypes for gene: BRAT1 were set to Neurodevelopmental disorder with cerebellar atrophy and with or without seizures MIM#618056; neonatal lethal rigidity and multifocal seizure syndrome MIM#614498
Review for gene: BRAT1 was set to AMBER
Added comment: Biallelic BRAT1 mutations cause a neurodevelopmental phenotype with evidence of marked genotype–phenotype correlation: homozygous null variants result in a severe phenotype, whereas compound heterozygosity for null/hypomorphic variants is associated with a milder phenotype. In one study one patient with homozygous hypomorphic variants was diagnosed as a congenital cerebral palsy due to spastic paraplegia.
Sources: Literature
Cerebral Palsy v1.36 BCL11A Luisa Weiss reviewed gene: BCL11A: Rating: GREEN; Mode of pathogenicity: None; Publications: 35856171, 33528536, 34077496; Phenotypes: Dias-Logan syndrome, MIM#617101; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.36 ATP8A2 Luisa Weiss gene: ATP8A2 was added
gene: ATP8A2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATP8A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATP8A2 were set to 35321980; 30542205; 34077496
Phenotypes for gene: ATP8A2 were set to Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome, MIM#615268
Review for gene: ATP8A2 was set to GREEN
Added comment: 4 individuals from 3 families with biallelic mutations in ATP8A2 and CP. 3/4 patients presented with intellectual disability.

PMID 35321980: Two sibling reported with a non-progressive dyskinetic cerebral palsy resembling cerebellar ataxia (athetotic movements, ptosis, ophthalmoplegia, hypotonia, delayed development)

PMID 30542205: One patient with atypical CP (atypical due to intellectual disability)because intell dis and typical neurologic pattern (hypertonia, ataxia or transient episodic exacerbations of neurologic symptoms)

PMID 34077496: One patient with CP and microcephaly likely due to simultaneously present biallelic CIT mutations
Sources: Literature
Cerebral Palsy v1.36 ATP7A Luisa Weiss gene: ATP7A was added
gene: ATP7A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATP7A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: ATP7A were set to 35322241; 33528536; 34788679
Phenotypes for gene: ATP7A were set to Menkes disease MIM#3094009
Review for gene: ATP7A was set to GREEN
Added comment: 3 individuals from 3 different publications with CP. Two patients were male with de novo splice affecting mutations. One patient was female with a heterozygous de novo frameshift mutation in ATP7B causative for the disease as described before for Menkes disease.
Sources: Literature
Cerebral Palsy v1.36 ATM Luisa Weiss gene: ATM was added
gene: ATM was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ATM were set to 34364746; 26380989; 34114234
Phenotypes for gene: ATM were set to Ataxia-telangiectasia, MIM#208900
Review for gene: ATM was set to GREEN
Added comment: 3 individuals presenting with CP and harboring biallelic compound heterozygous mutations in ATM. At least one the individual had an overlapping phenotype of CP with Ataxia Teleangiectasia
Sources: Literature
Cerebral Palsy v1.36 ARID2 Luisa Weiss gene: ARID2 was added
gene: ARID2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ARID2 were set to 33528536
Phenotypes for gene: ARID2 were set to Coffin-Siris syndrome, MIM#617808
Review for gene: ARID2 was set to GREEN
Added comment: Large cohort study with three individual cases with CP and de novo ARID2 mutations (2 nonsense and 1 frameshift mutation)
Sources: Literature
Cerebral Palsy v1.36 ARG1 Luisa Weiss gene: ARG1 was added
gene: ARG1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ARG1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ARG1 were set to 35505270; 34788679
Phenotypes for gene: ARG1 were set to Argininemia MIM#207800
Review for gene: ARG1 was set to GREEN
Added comment: Literature review: Three independent cases have been published with biallelic mutations in ARG1 and presenting with cerebral palsy. Two patients harbored a recurrent splice site mutation, one patient presented with compound heterozygous missense mutations.
Sources: Literature
Cerebral Palsy v1.36 AKT3 Luisa Weiss gene: AKT3 was added
gene: AKT3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AKT3 were set to 34354878; 30542205; 32989326
Review for gene: AKT3 was set to AMBER
Added comment: Two individual patients with CP and an AKT3 mutation have been published. In one of them (PMID 34354878) CP might be caused by birth asphyxia and is not be related to the AKT3 mutation. Additionally, there is functional data supporting the hypothesis that AKT3 might be a causative gene (PMID 32989326).

PMID 34354878: One patient described as presenting with MPPH and having a mutation in AKT3, while the mutation itself is not named (unknown whether LoF or missense, de novo or inherited). CP is listed as a coexisting feature in this patient which was caused by birth asphyxia due to umbilical cord strangulation around his neck.

30542205: One additional case with atypical CP (atypical due to major brain malformations and progressive neurologic disease) and a de novo missense mutation
Sources: Literature
Cerebral Palsy v1.36 AHDC1 Luisa Weiss gene: AHDC1 was added
gene: AHDC1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: AHDC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AHDC1 were set to 33528536
Phenotypes for gene: AHDC1 were set to Xia-Gibbs syndrome, MIM#615829
Review for gene: AHDC1 was set to GREEN
Added comment: 3 individuals in CP cohort with mono-allelic de novo variants (2 frameshift, 1 6-AA-deletion).

Other ADHC1 frameshift mutations have been known to cause an early onset neurological disorder with absent or poor expressive language, obstructive sleep apnea and brain abnormalities.
Sources: Literature
Cerebral Palsy v1.36 ADNP Luisa Weiss gene: ADNP was added
gene: ADNP was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ADNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADNP were set to 33528536
Phenotypes for gene: ADNP were set to Helsmoortel-van der Aa syndrome MIM#615873
Review for gene: ADNP was set to AMBER
Added comment: Large cohort study of cerebral palsy cases identified two variants in two individual patients with CP. One mutation was a recurrent Helsmoortel-van der Aa-syndrome nonsense mutation, the other was a de novo frameshift mutation. No further information about the patient's phenotype was given.
Sources: Literature
Cerebral Palsy v1.36 ACADM Luisa Weiss gene: ACADM was added
gene: ACADM was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ACADM was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACADM were set to 11263545; 35076175
Phenotypes for gene: ACADM were set to Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM# 201450
Review for gene: ACADM was set to AMBER
Added comment: Currently unclear if variants in this gene can cause CP. If so, CP is likely to happen as a secondary effect of the brain damage happening if Acyl-CoA dehydrogenase deficiency is not treated correctly or early enough.
According to one study, CP can be present in 9% of cases with biallelic mutations in ACADM, probably secondary to the underlying disease and associated with early-onset seizures (PMID 11263545).
In a second publication one other case of CP associated with biallelic mutations in ACADM was presented, but this patient's phenotype was likely caused by biallelic mutations in PDHX which were present simultaneously.
Sources: Literature
Cerebral Palsy v1.36 ACTB Luisa Weiss changed review comment from: Three independent cases in one cohort study.
Sources: Literature; to: Three independent cases in one cohort study.
Sources: Literature
Cerebral Palsy v1.36 ACTB Luisa Weiss gene: ACTB was added
gene: ACTB was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ACTB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: ACTB were set to 33528536
Phenotypes for gene: ACTB were set to Baraitser-Winter syndrome 1 MIM#243310
Review for gene: ACTB was set to GREEN
Added comment: Three independent cases in one cohort study.
Sources: Literature
Cerebral Palsy v1.36 ADCY5 Luisa Mackenroth gene: ADCY5 was added
gene: ADCY5 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ADCY5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ADCY5 were set to 33528536; 33098801
Phenotypes for gene: ADCY5 were set to Dyskinesia with orofacial involvement MIM#606703
Mode of pathogenicity for gene: ADCY5 was set to Other
Review for gene: ADCY5 was set to GREEN
Added comment: Multiple individuals reported in two different cohort studies analyzing children diagnosed with CP. Clinical overlap with childhood onset dystonia likely. Reported mutations in CP patients indicate gain-of-function mechanism, but loss-of-function mechanism has been described for allelic mutations.
Sources: Literature
Cerebral Palsy v1.33 ASXL3 Clare van Eyk reviewed gene: ASXL3: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 35863334, 33528536; Phenotypes: Bainbridge-Ropers syndrome (MIM #615485); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.32 ASXL1 Clare van Eyk gene: ASXL1 was added
gene: ASXL1 was added to Cerebral Palsy. Sources: Literature,Expert Review
Mode of inheritance for gene: ASXL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ASXL1 were set to 33528536; 30542205
Phenotypes for gene: ASXL1 were set to Bohring-Opitz syndrome (MIM 605039)
Review for gene: ASXL1 was set to GREEN
Added comment: 3 individuals with de novo loss of function variants identified in a retrospective CP cohort analysis (PMID 33528536) . One additional individual reported in PMID 30542205 with "atypical cerebral palsy".

Truncal hypotonia with spasticity of the extremities are sometimes reported in BOS (but are not characteristic of the disorder), along with multiple developmental abnormalities of varying severity.
Sources: Literature, Expert Review
Cerebral Palsy v1.31 ATP1A3 Clare van Eyk reviewed gene: ATP1A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536, 30542205; Phenotypes: Developmental and epileptic encephalopathy 99 (MIM# 619606); Mode of inheritance: None
Cerebral Palsy v1.31 ADAT3 Zornitza Stark Phenotypes for gene: ADAT3 were changed from MIM #615286 to Neurodevelopmental disorder with brain abnormalities, poor growth, and dysmorphic facies, MIM# 615286
Cerebral Palsy v1.29 ADAT3 Clare van Eyk changed review comment from: Homozygous founder variant in ADAT3 (p.V144M) reported in two cohort studies of children diagnosed with cerebral palsy (PMIDs 35076175; 34321325).

Tone abnormalities, including spasticity and hypotonia, are frequently reported in individuals from additional families with the same variant (PMID 26842963, 11 families, variant also called V128M) and are variable within families. Intellectual disability/developmental delay are always present and the majority with strabismus and growth failure.
Sources: Literature; to: Homozygous founder variant in ADAT3 (p.V144M) reported in two cohort studies of children diagnosed with cerebral palsy (PMIDs 35076175; 34321325).

Tone abnormalities, including spasticity and hypotonia, are frequently reported in individuals from additional families with the same variant (PMID 26842963, 11 families, variant also called V128M) and are variable within families. Intellectual disability/developmental delay are always present and the majority with strabismus and growth failure.
Sources: Literature
Cerebral Palsy v1.29 ADAT3 Clare van Eyk gene: ADAT3 was added
gene: ADAT3 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ADAT3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAT3 were set to 35076175; 34321325
Phenotypes for gene: ADAT3 were set to MIM #615286
Review for gene: ADAT3 was set to GREEN
Added comment: Homozygous founder variant in ADAT3 (p.V144M) reported in two cohort studies of children diagnosed with cerebral palsy (PMIDs 35076175; 34321325).

Tone abnormalities, including spasticity and hypotonia, are frequently reported in individuals from additional families with the same variant (PMID 26842963, 11 families, variant also called V128M) and are variable within families. Intellectual disability/developmental delay are always present and the majority with strabismus and growth failure.
Sources: Literature
Cerebral Palsy v1.28 ADAR Zornitza Stark Mode of inheritance for gene: ADAR was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.27 ELOVL1 Zornitza Stark Phenotypes for gene: ELOVL1 were changed from MIM 618527 to Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, MIM# 618527
Cerebral Palsy v1.24 ELOVL1 Zornitza Stark reviewed gene: ELOVL1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyotic keratoderma, spasticity, hypomyelination, and dysmorphic facies, MIM# 618527; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.23 ELOVL1 Clare van Eyk changed review comment from: Same novel heterozygous missense variant reported in 2 families (p.Ser165Phe, described twice in the literature, PMIDs 30487246 and 29496980) de novo in one family, unknown inheritance in a second) with similar phenotype which included icthyotic keratoderma, spasticity, hypomyelination and some dysmorphism. Fatty acid profile was altered in HEK293 cells transfected with mutant construct.

An additional 2 members of a consanguineous family both with cerebral palsy were described with a novel homozygous variant affecting splicing of ELOVL1 and similar clinical phenotype with earlier onset and more severe phenotype (PMID 35379526) . Heterozygous parents are unaffected. Patient skin samples show defects in very long chain fatty acid synthesis.
Sources: Literature; to: Same novel heterozygous missense variant reported in 2 families (p.Ser165Phe, described twice in the literature, PMIDs 30487246 and 29496980) de novo in one family, unknown inheritance in a second) with similar phenotype which included icthyotic keratoderma, spasticity, hypomyelination and some dysmorphism. Fatty acid profile was altered in HEK293 cells transfected with mutant construct.

An additional 2 members of a consanguineous family both with cerebral palsy were described with a novel homozygous variant affecting splicing of ELOVL1 and similar clinical phenotype with earlier onset and more severe phenotype (PMID 35379526) . Heterozygous parents are unaffected. Patient skin samples show defects in very long chain fatty acid synthesis.
Sources: Literature
Cerebral Palsy v1.23 ADAR Clare van Eyk reviewed gene: ADAR: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 34702576; Phenotypes: Aicardi-Goutieres syndrome 6, MIM#615010; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Cerebral Palsy v1.23 ELOVL1 Clare van Eyk gene: ELOVL1 was added
gene: ELOVL1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ELOVL1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications for gene: ELOVL1 were set to (PMID: 35379526; 30487246; 29496980)
Phenotypes for gene: ELOVL1 were set to MIM 618527
Review for gene: ELOVL1 was set to GREEN
Added comment: Same novel heterozygous missense variant reported in 2 families (p.Ser165Phe, described twice in the literature, PMIDs 30487246 and 29496980) de novo in one family, unknown inheritance in a second) with similar phenotype which included icthyotic keratoderma, spasticity, hypomyelination and some dysmorphism. Fatty acid profile was altered in HEK293 cells transfected with mutant construct.

An additional 2 members of a consanguineous family both with cerebral palsy were described with a novel homozygous variant affecting splicing of ELOVL1 and similar clinical phenotype with earlier onset and more severe phenotype (PMID 35379526) . Heterozygous parents are unaffected. Patient skin samples show defects in very long chain fatty acid synthesis.
Sources: Literature
Cerebral Palsy v1.23 SPTAN1 Zornitza Stark Phenotypes for gene: SPTAN1 were changed from Developmental and epileptic encephalopathy 5; OMIM #613477 to Developmental and epileptic encephalopathy 5; OMIM #613477; Hereditary spastic paraplegia MONDO:0019064, SPTAN1-related
Cerebral Palsy v1.22 SPTAN1 Chirag Patel edited their review of gene: SPTAN1: Added comment: Leveille et al (2019) - 2 patients with HSP with biallelic missense SPTAN1 variants Previously described zebrafish, mouse, and rat animal models of SPTAN1 deficiency, all consistently showing axonal degeneration, fitting the pathological features of HSP in humans.

Xie et al (2022) - 1 patient with complicated HSP and homozygous SPTAN1 mutation. Healthy parents and sister all carried the heterozygous mutation.

Van de Vondel et al (2022) - 22 patients from 14 families with five novel heterozygous SPTAN1 variants. Presentations ranged from cerebellar ataxia, intellectual disability, epilepsy, and spastic paraplegia. A recurrent missense mutation (p.Arg19Trp) in 15 patients with spastic paraplegia. Through protein modeling they showed that mutated amino acids are located at crucial interlinking positions, interconnecting the three-helix bundle of a spectrin repeat.; Changed publications: PMID: 35150594, 34526651, 31515523; Changed phenotypes: Spastic Paraplegia
Cerebral Palsy v1.21 SCN2A Clare van Eyk gene: SCN2A was added
gene: SCN2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SCN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN2A were set to 33528536; 29761117; 34114234
Phenotypes for gene: SCN2A were set to Developmental and epileptic encephalopathy 11 (DEE11), MIM# 613721
Review for gene: SCN2A was set to GREEN
Added comment: Four single cases with de novo pathogenic/likely pathogenic missense variants in individuals with a clinical diagnosis of cerebral palsy. Mutations in SCN2A cause a spectrum of early-onset epileptic encephalopathies, with some cases reported to have movement disorders clinically overlapping with cerebral palsy.
Sources: Literature
Cerebral Palsy v1.20 AUTS2 Zornitza Stark edited their review of gene: AUTS2: Changed phenotypes: Intellectual developmental disorder, autosomal dominant 26, MIM# 615834
Cerebral Palsy v1.20 TNR Zornitza Stark Phenotypes for gene: TNR were changed from Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus to Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus, MIM# 619653; Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus
Cerebral Palsy v1.19 TNR Zornitza Stark edited their review of gene: TNR: Changed phenotypes: Neurodevelopmental disorder, nonprogressive, with spasticity and transient opisthotonus, MIM# 619653, Spastic para- or tetraparesis, Axial muscular hypotonia, Intellectual disability, Transient opisthotonus
Cerebral Palsy v1.19 SPATA5L1 Zornitza Stark Phenotypes for gene: SPATA5L1 were changed from Intellectual disability; spastic-dystonic cerebral palsy; epilepsy; hearing loss to Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616
Cerebral Palsy v1.18 SPATA5L1 Zornitza Stark reviewed gene: SPATA5L1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with hearing loss and spasticity, MIM# 619616; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.17 SPATA5L1 Paul De Fazio gene: SPATA5L1 was added
gene: SPATA5L1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SPATA5L1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPATA5L1 were set to 34626583
Phenotypes for gene: SPATA5L1 were set to Intellectual disability; spastic-dystonic cerebral palsy; epilepsy; hearing loss
Review for gene: SPATA5L1 was set to GREEN
gene: SPATA5L1 was marked as current diagnostic
Added comment: 47 individuals from 26 unrelated families from various ethnicities with biallelic variants reported. Phenotypes include ID, hearing impairment, movement disorder, abnormal MRI, hypotonia, visual impairment, epilepsy, and microcephaly.

Approximately two-thirds of individuals had spastic-dystonic cerebral palsy.
Sources: Literature
Cerebral Palsy v1.16 NSRP1 Zornitza Stark reviewed gene: NSRP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v1.16 NSRP1 Krithika Murali gene: NSRP1 was added
gene: NSRP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NSRP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NSRP1 were set to 34385670
Phenotypes for gene: NSRP1 were set to Epilepsy; Cerebral palsy; microcephaly; Intellectual disability
Review for gene: NSRP1 was set to AMBER
Added comment: Novel gene regulating splicing. Biallelic LoF pathogenic variants reported in 6 individuals from 3 unrelated families associated with a phenotype characterized by developmental delay, epilepsy, microcephaly, and spastic cerebral palsy.
Sources: Literature
Cerebral Palsy v1.14 WDR45 Chirag Patel gene: WDR45 was added
gene: WDR45 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: WDR45 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: WDR45 were set to PMID: 33528536, 34364746
Phenotypes for gene: WDR45 were set to Neurodegeneration with brain iron accumulation 5, OMIM # 300894
Review for gene: WDR45 was set to GREEN
Added comment: Established gene for neurodevelopmental/degenerative disorder with spasticity and dystonia. Moreno-De-Luca et al. (2021) reported 4 patients with CP with P/LP variants.
Zahrani et al. (2021) reported 2 patients with dystonic/hypotonic CP with variants.
Sources: Literature
Cerebral Palsy v1.9 ZEB2 Chirag Patel gene: ZEB2 was added
gene: ZEB2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZEB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZEB2 were set to PMID: 33528536, 33098801
Phenotypes for gene: ZEB2 were set to Mowat-Wilson syndrome, OMIM # 235730
Review for gene: ZEB2 was set to GREEN
Added comment: Neurodevelopmental disorder with DD, ID, epilepsy, and dysmorphism.
Moreno-De-Luca et al. (2021) reported 3 patients with CP with P/LP variants.
Zech et al. (2020) reported 1 patient with dystonic CP with de novo variant.
Sources: Literature
Cerebral Palsy v1.7 UBE3A Chirag Patel gene: UBE3A was added
gene: UBE3A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: UBE3A was set to MONOALLELIC, autosomal or pseudoautosomal, paternally imprinted (maternal allele expressed)
Publications for gene: UBE3A were set to PMID: 33528536
Phenotypes for gene: UBE3A were set to Angelman syndrome , OMIM #105830
Review for gene: UBE3A was set to GREEN
Added comment: Neurodevelopmental disorder with DD, ID, epilepsy, and ataxia. Moreno-De-Luca et al. (2021) reported 3 patients with CP with P/LP variants.
Sources: Literature
Cerebral Palsy v1.6 TUBB2B Chirag Patel reviewed gene: TUBB2B: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v1.4 TUBB4A Chirag Patel gene: TUBB4A was added
gene: TUBB4A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBB4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB4A were set to PMID: 34531397, 33528536
Phenotypes for gene: TUBB4A were set to Dystonia 4, torsion, autosomal dominant, OMIM #128101; Leukodystrophy, hypomyelinating, 6, OMIM # 612438
Review for gene: TUBB4A was set to GREEN
Added comment: Van Eyk et al. (2021) reported 1 patient with dystonic CP with de novo variant. Moreno-De-Luca et al. (2021) reported 6 patients with CP with P/LP variants.
Sources: Literature
Cerebral Palsy v1.3 TUBB2B Chirag Patel Deleted their review
Cerebral Palsy v1.3 TUBB2B Chirag Patel gene: TUBB2B was added
gene: TUBB2B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TUBB2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TUBB2B were set to PMID: 33528536
Phenotypes for gene: TUBB2B were set to Cortical dysplasia, complex, with other brain malformations 7, OMIM # 610031
Review for gene: TUBB2B was set to RED
Added comment: Moreno-De-Luca et al. (2021) reported 3 patients with cerebral palsy with de novo pathogenic/LP variants BUT primarily presents with cortical malformations
Sources: Literature
Cerebral Palsy v1.0 TCF4 Chirag Patel reviewed gene: TCF4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33528536; Phenotypes: Pitt-Hopkins syndrome, MIM# 610954; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.187 STXBP1 Zornitza Stark gene: STXBP1 was added
gene: STXBP1 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: STXBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: STXBP1 were set to 29761117
Phenotypes for gene: STXBP1 were set to Developmental and epileptic encephalopathy 4, MIM# 612164
Review for gene: STXBP1 was set to GREEN
Added comment: ID and seizures, though spastic quadriplegia reported, and variants identified as part of CP cohorts.
Sources: Expert Review
Cerebral Palsy v0.180 SAMHD1 Chirag Patel gene: SAMHD1 was added
gene: SAMHD1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SAMHD1 were set to PMID: 19525956
Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres syndrome 5; OMIM #612952
Review for gene: SAMHD1 was set to GREEN
Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood.

Rice et al. (2009) reported biallelic SAMHD1 mutations in 13 families with AGS.
Sources: Literature
Cerebral Palsy v0.178 RNASEH2C Chirag Patel gene: RNASEH2C was added
gene: RNASEH2C was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RNASEH2C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2C were set to PMID: 17846997
Phenotypes for gene: RNASEH2C were set to Aicardi-Goutieres syndrome 3; OMIM #610329
Review for gene: RNASEH2C was set to GREEN
Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood.

Rice et al. (2007) reported biallelic RNASEH2C mutations in 18 families with AGS.
Sources: Literature
Cerebral Palsy v0.176 RNASEH2A Chirag Patel gene: RNASEH2A was added
gene: RNASEH2A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RNASEH2A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2A were set to PMID: 17846997
Phenotypes for gene: RNASEH2A were set to Aicardi-Goutieres syndrome 4; OMIM #610333
Review for gene: RNASEH2A was set to GREEN
Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood.

Rice et al. (2007) reported biallelic RNASEH2A mutations in 3 families with AGS.
Sources: Literature
Cerebral Palsy v0.175 RNASEH2B Chirag Patel gene: RNASEH2B was added
gene: RNASEH2B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNASEH2B were set to PMID: 17846997, 28762473
Phenotypes for gene: RNASEH2B were set to Aicardi-Goutieres syndrome 2; OMIM #610181
Review for gene: RNASEH2B was set to GREEN
Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood.

Rice et al. (2007) reported biallelic RNASEH2B mutations in 47 families with AGS.

Svingen et al. (2017) reported 2 siblings with atypical AGS with spastic quadriplegia, anarthria, preserved intellect, and increased iron signal in basal ganglia and homozygous RNASEH2B pathogenic variant.
Sources: Literature
Cerebral Palsy v0.173 TREX1 Chirag Patel gene: TREX1 was added
gene: TREX1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: TREX1 were set to PMID: 17846997, 33528536
Phenotypes for gene: TREX1 were set to Aicardi-Goutieres syndrome 1, dominant and recessive, OMIM #225750
Review for gene: TREX1 was set to GREEN
Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood.

Rice et al. (2007) reported biallelic TREX1 mutations in 31 families with AGS, and de novo heterozygous TREX1 mutation in 1 patient with AGS.

Moreno-De-Luca et al. (2021) reported 1 patient with CP and paternally inherited pathogenic variant.
Sources: Literature
Cerebral Palsy v0.171 TAF1 Chirag Patel gene: TAF1 was added
gene: TAF1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: TAF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: TAF1 were set to PMID: 26637982, 33528536, 17273961
Phenotypes for gene: TAF1 were set to Intellectual developmental disorder, X-linked syndromic 33, OMIM #300966; Dystonia-Parkinsonism, X-linked, OMIM #314250
Review for gene: TAF1 was set to GREEN
Added comment: O'Rawe et al. (2015) reported 12 boys from 9 unrelated families with X-linked global developmental delay, intellectual disability, dysmorphism, generalized hypotonia, microcephaly and variable neurologic features (hypoplastic CC, spastic diplegia, dystonic movements, tremors). They identified 9 different hemizygous mutations in TAF1 gene (most de novo, 3 maternally inherited). No functional studies. The mutations were found by WGS, WES, targeted panel and microarray, and all confirmed by Sanger sequencing.

Moreno-De-Luca et al. (2021) reported 2 patients with CP and de novo LP variant.

Note: X-linked dystonia-parkinsonism (XDP) is caused by an SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) retrotransposon insertion in intron 32 of TAF1, which encodes the largest component of the TFIID complex, and resulted in significantly decreased expression levels of TAF1 and the dopamine receptor D2 gene (DRD2) in the caudate nucleus.
Sources: Literature
Cerebral Palsy v0.168 SPTAN1 Chirag Patel gene: SPTAN1 was added
gene: SPTAN1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SPTAN1 were set to PMID: 20493457, 33528536, 34364746
Phenotypes for gene: SPTAN1 were set to Developmental and epileptic encephalopathy 5; OMIM #613477
Review for gene: SPTAN1 was set to GREEN
Added comment: Developmental and epileptic encephalopathy-5 (DEE5) is a neurologic disorder characterised by tonic seizures/infantile spasms in first months of life, global developmental delay, lack of visual attention, poor head control, feeding difficulties, microcephaly, and spastic quadriplegia. Brain imaging may show cerebral atrophy and hypomyelination.

Saitsu et al (2010) reported 2 patients with de novo in-frame mutations of SPTAN1 with early-onset WS with spastic quadriplegia, poor visual attention, and severe developmental delay.
Moreno-De-Luca et al (2021) reported 3 patients with CP with de novo LP/P variants.
Zahrani et al (2021) reported 1 patient with NDD (CP features) with de novo LP variant
Sources: Literature
Cerebral Palsy v0.166 ZSWIM6 Chirag Patel gene: ZSWIM6 was added
gene: ZSWIM6 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ZSWIM6 were set to PMID: 29198722
Phenotypes for gene: ZSWIM6 were set to Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features, OMIM #617865
Review for gene: ZSWIM6 was set to GREEN
Added comment: Palmer et al. (2017) reported 7 unrelated patients with neurodevelopmental disorder with movement abnormalities spasticity, abnormal gait, and autistic features. WES/WGS identified the same heterozygous R913X variant in exon 13 of ZSWIM6 gene (de novo in 6, unk in 1). The mutation was not found in gnomAD. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein.

Note: de novo missense variant within C-terminal Sin3-like domain of ZSWIM6 reported to cause acromelic frontonasal dysostosis (AFND), via a proposed gain-of-function effect.
Sources: Literature
Cerebral Palsy v0.165 SCN8A Zornitza Stark Phenotypes for gene: SCN8A were changed from to Cerebral Palsy; Epileptic encephalopathy 13 MIM# 614558; Cognitive impairment with or without cerebellar ataxia MIM# 614306
Cerebral Palsy v0.162 SCN8A Danielle Ariti reviewed gene: SCN8A: Rating: GREEN; Mode of pathogenicity: Other; Publications: 33528536, 32989326, 31904124; Phenotypes: Cerebral Palsy, Epileptic encephalopathy 13 MIM# 614558, Cognitive impairment with or without cerebellar ataxia MIM# 614306; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.161 MFN2 Krithika Murali gene: MFN2 was added
gene: MFN2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MFN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MFN2 were set to 16437557; 21715711; 34114234; 33528536
Phenotypes for gene: MFN2 were set to Charcot-Marie-Tooth disease, axonal, type 2A2A - #609260; Charcot-Marie-Tooth disease, axonal, type 2A2B - #617087; Hereditary motor and sensory neuropathy VIA - 601152
Review for gene: MFN2 was set to RED
Added comment: Most common cause of axonal Charcot-Marie-Tooth disease (CMT2). Homozygous and compound heterozygous MFN2 mutations have been reported in early-onset CMT2, including patients diagnosed <12 months of age.

x1 het VUS reported in a prematurely born child with unilateral spastic CP (34114234)
x1 paternally inherited pathogenic variant in MFN2 reported in 1 patient in CP cohort (33528536)
Sources: Literature
Cerebral Palsy v0.157 MECP2 Krithika Murali gene: MECP2 was added
gene: MECP2 was added to Cerebral Palsy. Sources: Expert list,Literature
Mode of inheritance for gene: MECP2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: MECP2 were set to 30542205; 33528536
Phenotypes for gene: MECP2 were set to Encephalopathy, neonatal severe - 300673; Intellectual developmental disorder, X-linked syndromic, Lubs type - 300260; Intellectual developmental disorder, X-linked, syndromic 13 - 300055; Rett syndrome - 312750
Review for gene: MECP2 was set to GREEN
Added comment: Pathogenic/likely pathogenic variants reported in 9 unrelated patients with CP
Sources: Expert list, Literature
Cerebral Palsy v0.157 MAOB Krithika Murali gene: MAOB was added
gene: MAOB was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MAOB was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: MAOB were set to 31700678
Review for gene: MAOB was set to RED
Added comment: Identified in 2 unrelated individuals with CP (with same variant also identified in unaffected monozygotic twin) in a gene not currently known to be associated disease.
Sources: Literature
Cerebral Palsy v0.157 KMT2B Krithika Murali gene: KMT2B was added
gene: KMT2B was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: KMT2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2B were set to 29697234
Phenotypes for gene: KMT2B were set to Dystonia 28, childhood-onset - #617284
Review for gene: KMT2B was set to RED
Added comment: Progressive early-onset movement disorder (mean age 7 years). Variants not previously reported in patients with CP.
Sources: Literature
Cerebral Palsy v0.157 KMT2A Krithika Murali gene: KMT2A was added
gene: KMT2A was added to Cerebral Palsy. Sources: Expert list,Literature
Mode of inheritance for gene: KMT2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KMT2A were set to 33528536
Phenotypes for gene: KMT2A were set to Wiedemann-Steiner syndrome - #605130
Review for gene: KMT2A was set to GREEN
Added comment: Pathogenic/likely pathogenic variants identified in 5 unrelated patients with CP (Moreno-de-Luca et al 2021).
Sources: Expert list, Literature
Cerebral Palsy v0.157 KIDINS220 Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap with CP particularly for mono-allelic disease association.
Cerebral Palsy v0.156 KIDINS220 Krithika Murali gene: KIDINS220 was added
gene: KIDINS220 was added to Cerebral Palsy. Sources: Expert list,Literature
Mode of inheritance for gene: KIDINS220 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KIDINS220 were set to 30542205
Phenotypes for gene: KIDINS220 were set to Spastic paraplegia, intellectual disability, nystagmus, and obesity - #617296; Ventriculomegaly and arthrogryposis - #619501
Review for gene: KIDINS220 was set to GREEN
Added comment: Well-established association with AD spastic paraplegia and AR ventriculomegaly and arthrogryposis - phenotypic overlap noted with CP.

Also reported in 2 siblings with atypical CP likely due to parental germline mosaicism (PMID 30542205)

Alternative gene names: ARMS
Sources: Expert list, Literature
Cerebral Palsy v0.154 KCNQ2 Zornitza Stark reviewed gene: KCNQ2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Developmental and epileptic encephalopathy 7 - #613720; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.154 KCNQ2 Zornitza Stark Phenotypes for gene: KCNQ2 were changed from Developmental and epileptic encephalopathy 7 - #613720; Myokymia - #121200; Seizures, benign neonatal, 1 - #121200 to Developmental and epileptic encephalopathy 7 - #613720
Cerebral Palsy v0.152 KDM7A Krithika Murali changed review comment from: Synonyms: JHDMID, KDM7, KIAA1718

De novo missense VUS identified in a WES CP cohort study in a gene not known to be associated with disease.
Sources: Expert list, Literature; to: Synonyms: JHDMID, KDM7, KIAA1718

De novo missense VUS identified in a WES CP cohort study in a gene not known to be associated with disease.
Sources: Literature
Cerebral Palsy v0.152 KDM7A Krithika Murali gene: KDM7A was added
gene: KDM7A was added to Cerebral Palsy. Sources: Expert list,Literature
Mode of inheritance for gene: KDM7A was set to Unknown
Publications for gene: KDM7A were set to 25666757
Review for gene: KDM7A was set to RED
Added comment: Synonyms: JHDMID, KDM7, KIAA1718

De novo missense VUS identified in a WES CP cohort study in a gene not known to be associated with disease.
Sources: Expert list, Literature
Cerebral Palsy v0.152 KCNQ2 Krithika Murali gene: KCNQ2 was added
gene: KCNQ2 was added to Cerebral Palsy. Sources: Expert list,Literature
Mode of inheritance for gene: KCNQ2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: KCNQ2 were set to 33557955; 32585800; 22275249; 28655139
Phenotypes for gene: KCNQ2 were set to Developmental and epileptic encephalopathy 7 - #613720; Myokymia - #121200; Seizures, benign neonatal, 1 - #121200
Review for gene: KCNQ2 was set to AMBER
Added comment: Well-validated association with early-onset epileptic encephalopathy (ClinGen) and neonatal seizures.


In addition, KCNQ2 pathogenic variants reported in multiple individuals with intractable neonatal seizures and associated intellectual disability, developmental delay and motor impairment (axial hypotonia and/or spastic quadriplegia) - (PMID 22275249)

x2 case reports of associated CP - 6 year old M with neonatal seizures and a CP-like syndrome. KCNQ2 exon 7 partial duplication impairing gene function (ClinVar ID 617505) - (PMID 32585800 and 33557955) and 2 year old F with perinatal encephalopathy, severe tetraparesis and cerebral visual impairment (PMID 28655139). Neonatal epileptic encephalopathy primary presentation in both cases.

On Expert CP Gene List.
Sources: Expert list, Literature
Cerebral Palsy v0.149 ITPR1 Zornitza Stark gene: ITPR1 was added
gene: ITPR1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: ITPR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ITPR1 were set to 28826917; 25981959; 22986007
Phenotypes for gene: ITPR1 were set to Spinocerebellar ataxia 29, congenital nonprogressive MIM#117360
Review for gene: ITPR1 was set to GREEN
Added comment: Variants in this gene reported in individuals diagnosed with ataxic CP.
Sources: Expert list
Cerebral Palsy v0.148 IQSEC2 Zornitza Stark gene: IQSEC2 was added
gene: IQSEC2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: IQSEC2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: IQSEC2 were set to 33368194; 20473311; 23674175
Phenotypes for gene: IQSEC2 were set to Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Review for gene: IQSEC2 was set to RED
Added comment: More than 20 unrelated families reported. Typical features are ID, microcephaly and hand stereotypies. Phenotypic overlap with Angelman-Rett-like syndromes rather than CP.
Sources: Expert list
Cerebral Palsy v0.147 HPCA Zornitza Stark changed review comment from: Isolated dystonia, variable age of onset, including in adolescence. Insufficient phenotypic overlap with CP.
Sources: Expert list; to: Four families reported. Isolated dystonia, variable age of onset, including in adolescence. Insufficient phenotypic overlap with CP.
Sources: Expert list
Cerebral Palsy v0.147 HPCA Zornitza Stark gene: HPCA was added
gene: HPCA was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: HPCA was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPCA were set to 30145809; 25799108
Phenotypes for gene: HPCA were set to Dystonia 2, torsion, autosomal recessive, MIM#224500
Review for gene: HPCA was set to RED
Added comment: Isolated dystonia, variable age of onset, including in adolescence. Insufficient phenotypic overlap with CP.
Sources: Expert list
Cerebral Palsy v0.145 MINPP1 Zornitza Stark edited their review of gene: MINPP1: Changed phenotypes: Pontocerebellar hypoplasia, type 16, MIM# 619527
Cerebral Palsy v0.144 ZC4H2 Zornitza Stark changed review comment from: Intellectual disability and spasticity are key features. At least one family had a diagnosis of CP.; to: Intellectual disability and spasticity are key features, more than 40 families reported. At least one family had a diagnosis of CP.
Cerebral Palsy v0.144 ZC4H2 Zornitza Stark edited their review of gene: ZC4H2: Changed publications: 23623388, 34322088, 33949289, 31885220, 31206972
Cerebral Palsy v0.142 ZC4H2 Zornitza Stark Mode of inheritance for gene: ZC4H2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v0.141 ZC4H2 Zornitza Stark reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23623388; Phenotypes: Wieacker-Wolff syndrome, MIM# 314580; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v0.140 SPG11 Zornitza Stark gene: SPG11 was added
gene: SPG11 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: SPG11 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPG11 were set to 34183250; 33581793
Phenotypes for gene: SPG11 were set to Spastic paraplegia 11, autosomal recessive, MIM# 604360
Review for gene: SPG11 was set to GREEN
Added comment: Intellectual disability and spasticity, reported in CP cohort.

Recent review of >300 individuals with SPG11-related disease. Mean age at onset was 13.10 ± 3.65 years, with initial symptoms like gait disturbance (107/195, 54.87%) and intellectual disability (47/195, 24.10%). Cognitive decline (228/270, 84.44%) was the most common complex manifestation stepped by dysarthria (134/195, 68.72%), neuropathy (112/177, 63.28%), amyatrophy, sphincter disturbance (60/130, 46.15%) and ataxia (90/194, 46.39%).
Sources: Expert list
Cerebral Palsy v0.139 SMARCB1 Zornitza Stark gene: SMARCB1 was added
gene: SMARCB1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: SMARCB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: SMARCB1 were set to Coffin-Siris syndrome 3, MIM# 614608
Review for gene: SMARCB1 was set to RED
Added comment: Intellectual disability and dysmorphic features, no strong phenotypic overlap with CP.
Sources: Expert list
Cerebral Palsy v0.134 PAK3 Zornitza Stark reviewed gene: PAK3: Rating: RED; Mode of pathogenicity: None; Publications: 25666757; Phenotypes: Intellectual developmental disorder, X-linked 30, MIM# 300558; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v0.133 SLC2A1 Zornitza Stark gene: SLC2A1 was added
gene: SLC2A1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: SLC2A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: SLC2A1 were set to 30799092; 18451999; 20129935; 10980529; 20221955; 31196579
Phenotypes for gene: SLC2A1 were set to GLUT1 deficiency syndrome 1, infantile onset, severe, 606777; GLUT1 deficiency syndrome 2, childhood onset, 612126; Disorders of glucose transport
Review for gene: SLC2A1 was set to GREEN
Added comment: Well established gene-disease association. Mixture of ID and movement disorders, reported in a CP cohort. Treatable.
Sources: Expert list
Cerebral Palsy v0.129 SCN1A Clare van Eyk gene: SCN1A was added
gene: SCN1A was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: SCN1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SCN1A were set to PMID: 33528536; PMID: 34364746; PMID: 34114234
Phenotypes for gene: SCN1A were set to Developmental and epileptic encephalopathy 6B, non-Dravet (OMIM 619317); Dravet syndrome (OMIM 607208)
Review for gene: SCN1A was set to GREEN
Added comment: Six cases described with missense (3 cases) or loss of function (3 cases) variants in SCN1A in individuals diagnosed with cerebral palsy. Mutations in SCN1A cause a spectrum of early-onset epileptic encephalopathies, with some cases reported to have movement disorders clinically overlapping with cerebral palsy.
Sources: Literature
Cerebral Palsy v0.129 PURA Clare van Eyk gene: PURA was added
gene: PURA was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PURA was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: PURA were set to PMID: 34077496
Phenotypes for gene: PURA were set to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Review for gene: PURA was set to GREEN
Added comment: PURA loss of function and missense variants cause a clinically variable neurodevelopmental disorder with movement disorders including dystonia and limb spasticity described in some individuals. One case with a novel frameshift deletion described with dyskinetic cerebral palsy and intellectual disability. An additional 3 cases with de novo variants (1 nonsense, 2 missense) reported in a retrospective analysis of a Clinical Laboratory referral cohort with cerebral palsy.
Sources: Literature
Cerebral Palsy v0.129 HECW2 Danielle Ariti gene: HECW2 was added
gene: HECW2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: HECW2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: HECW2 were set to 33528536; 33098801
Phenotypes for gene: HECW2 were set to Cerebral Palsy; Neurodevelopmental disorder with hypotonia, seizures, and absent language MIM# 617268
Review for gene: HECW2 was set to GREEN
Added comment: 3 individuals in CP cohort with mono-allelic (2x de novo & 1 unknown inheritance) HECW2 variants. All individuals were diagnosed with idiopathic dystonic CP.

HECW2 variants cause a neurodevelopmental disorder NDHSAL that presents with severe developmental delay, absent speech, epilepsy, encephalopathy, hypotonia, dystonia/dyskinesia, and macrocephaly.
Sources: Expert list
Cerebral Palsy v0.129 SHANK3 Zornitza Stark gene: SHANK3 was added
gene: SHANK3 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: SHANK3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SHANK3 were set to 17173049
Phenotypes for gene: SHANK3 were set to Phelan-McDermid syndrome, MIM# 606232
Review for gene: SHANK3 was set to RED
Added comment: Note deletions are common. ID with severe speech impairment/autistic features but movement disorders are not prominent, so limited overlap clinically with CP.
Sources: Expert list
Cerebral Palsy v0.121 GRIN2B Danielle Ariti gene: GRIN2B was added
gene: GRIN2B was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: GRIN2B was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GRIN2B were set to 34531397; 33528536
Phenotypes for gene: GRIN2B were set to Cerebral Palsy; Developmental and epileptic encephalopathy 27 MIM# 616139; Intellectual developmental disorder, autosomal dominant 6, with or without seizures MIM# 613970
Review for gene: GRIN2B was set to GREEN
Added comment: 3 individuals in CP cohort with mono-allelic (2x de novo & 1 unknown inheritance) GRIN2B variants.

GRIN2B variants cause autosomal dominant neurodevelopmental disorders DEE27 and MRD6 that present with intellectual disability, seizures, hypotonia, movement disorders, and autistic features.
Sources: Expert list
Cerebral Palsy v0.121 GNB1 Danielle Ariti gene: GNB1 was added
gene: GNB1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: GNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB1 were set to 33528536; 32989326; 34531397; 30194818
Phenotypes for gene: GNB1 were set to Cerebral Palsy; Mental retardation, autosomal dominant 42 MIM# 616973
Review for gene: GNB1 was set to GREEN
Added comment: 4 individuals in CP cohort reported with mono-allelic (3x de novo & 1x unknown inheritance) GNB1 variants. All individuals presented with impaired movement (dystonia, spasticity) and ID; additional features were growth delay, ADHD and seizures.

Additionally, all individuals had substitution affecting the p.Ile80 residue in exon 6 (28% of MRD42 cases carry variants at this residue and tend to present with Dystonia and growth delay more frequently than other residue-variant cases)
Sources: Expert list
Cerebral Palsy v0.121 GNAO1 Danielle Ariti gene: GNAO1 was added
gene: GNAO1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: GNAO1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNAO1 were set to 33528536; 34364746; 33098801
Phenotypes for gene: GNAO1 were set to Cerebral Palsy; Neurodevelopmental disorder with involuntary movements MIM# 617493
Review for gene: GNAO1 was set to GREEN
Added comment: >10 individuals in CP cohort reported with mono-allelic (de novo) GNAO1variants.
The majority of these individuals were diagnosed with Dyskinetic CP displaying progressive movement disorder (dystonia, athetosis and chorea), ID and often seizures.
Sources: Expert list
Cerebral Palsy v0.121 FOXG1 Danielle Ariti gene: FOXG1 was added
gene: FOXG1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: FOXG1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FOXG1 were set to 34077496; 33528536
Phenotypes for gene: FOXG1 were set to Cerebral Palsy; Rett syndrome, congenital variant MIM# 613454
Review for gene: FOXG1 was set to GREEN
Added comment: 5 individuals in CP cohort reported with mono-allelic (de novo) FOXG1 variants.
All individuals presented with movement impairments (3 with Spastic quadriplegia), intellectual disability, and microcephaly (and 2 individuals with seizures).
Sources: Expert list
Cerebral Palsy v0.121 PIGN Clare van Eyk changed review comment from: Two cases with compound heterozygous missense variants in PIGN were identified in a retrospective reanalysis of a large Clinical Laboratory referral cohort with cerebral palsy. Limb hypertonia and spasticity have been described in some children with Multiple congenital anomalies-hypotonia-seizures syndrome 1. Most children with Multiple congenital anomalies-hypotonia-seizures syndrome 1 die before 3 years of age, however missense variants have been reported to cause a less severe clinical phenotype.An additional case with a homozygous missense variant in PIGN was described to have atypical cerebral palsy with multiple other anomalies.; to: Two cases with compound heterozygous missense variants in PIGN were identified in a retrospective reanalysis of a large Clinical Laboratory referral cohort with cerebral palsy. Limb hypertonia and spasticity have been described in some children with Multiple congenital anomalies-hypotonia-seizures syndrome 1. Most children with Multiple congenital anomalies-hypotonia-seizures syndrome 1 die before 3 years of age, however missense variants have been reported to cause a less severe clinical phenotype. An additional case with a homozygous missense variant in PIGN was described to have atypical cerebral palsy with multiple other anomalies.
Cerebral Palsy v0.121 PIGN Clare van Eyk Deleted their comment
Cerebral Palsy v0.121 PIGN Clare van Eyk edited their review of gene: PIGN: Added comment: Two cases with compound heterozygous missense variants in PIGN were identified in a retrospective reanalysis of a large Clinical Laboratory referral cohort with cerebral palsy. Limb hypertonia and spasticity have been described in some children with Multiple congenital anomalies-hypotonia-seizures syndrome 1. Most children with Multiple congenital anomalies-hypotonia-seizures syndrome 1 die before 3 years of age, however missense variants have been reported to cause a less severe clinical phenotype.An additional case with a homozygous missense variant in PIGN was described to have atypical cerebral palsy with multiple other anomalies.; Changed rating: GREEN; Changed publications: PMID: 33528536, PMID: 34540776
Cerebral Palsy v0.121 PIGN Clare van Eyk gene: PIGN was added
gene: PIGN was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PIGN was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PIGN were set to PMID: 33528536
Phenotypes for gene: PIGN were set to Multiple congenital anomalies-hypotonia-seizures syndrome 1 (OMIM 614080)
Review for gene: PIGN was set to AMBER
Added comment: Two cases with compound heterozygous missense variants in PIGN were identified in a retrospective reanalysis of a large Clinical Laboratory referral cohort with cerebral palsy. Limb hypertonia and spasticity have been described in some children with Multiple congenital anomalies-hypotonia-seizures syndrome 1. Most children with Multiple congenital anomalies-hypotonia-seizures syndrome 1 die before 3 years of age, however missense variants have been reported to cause a less severe clinical phenotype.
Sources: Literature
Cerebral Palsy v0.121 PCDH19 Clare van Eyk changed review comment from: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. One male with spastic diplegic cerebral palsy described with a hemizygous predicted pathogenic variant.
Sources: Literature; to: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. One male with spastic diplegic cerebral palsy described with a hemizygous predicted pathogenic variant.
Sources: Literature
Cerebral Palsy v0.121 PCDH19 Clare van Eyk gene: PCDH19 was added
gene: PCDH19 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PCDH19 was set to Other
Publications for gene: PCDH19 were set to PMID: 34321325
Phenotypes for gene: PCDH19 were set to Developmental and epileptic encephalopathy 9 (OMIM 300088)
Review for gene: PCDH19 was set to RED
Added comment: Variants in PCDH19 cause an X-linked disorder which affects heterozygous females, with hemizygous males largely unaffected. One male with spastic diplegic cerebral palsy described with a hemizygous predicted pathogenic variant.
Sources: Literature
Cerebral Palsy v0.121 PCDH12 Clare van Eyk gene: PCDH12 was added
gene: PCDH12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PCDH12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PCDH12 were set to PMID: 34321325; PMID: 29556033
Phenotypes for gene: PCDH12 were set to Diencephalic-mesencephalic junction dysplasia syndrome 1 (OMIM 251280)
Review for gene: PCDH12 was set to GREEN
Added comment: One case with homozygous nonsense variant reported with dysmorphic features, dystonic cerebral palsy and comorbidities including intellectual disability. Second individual with compound heterozygous truncating PCDH12 variants diagnosed as dyskinetic cerebral palsy with epilepsy and severe intellectual disability. Biallelic PCDH12 mutations cause a syndromic neurodevelopmental disorder with spasticity or dystonia.
Sources: Literature
Cerebral Palsy v0.116 ECHS1 Danielle Ariti gene: ECHS1 was added
gene: ECHS1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: ECHS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ECHS1 were set to 33528536; 34364746; 32858208
Phenotypes for gene: ECHS1 were set to Cerebral Palsy; Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency MIM# 616277
Review for gene: ECHS1 was set to GREEN
Added comment: Two cases in CP cohort reported with compound heterozygous ECHS1variants.
One of the individuals presented with delayed motor skills with coordination problems, dystonia (at age 11), and spasticity in upper and lower limbs.

ECHS1 variants cause an inborn error of metabolism disorder characterised by severely delayed psychomotor development, neurodegeneration, increased lactic acid, and brain lesions in the basal ganglia. Some of these cases display paroxysmal and non-paroxysmal dystonia.
Sources: Expert list
Cerebral Palsy v0.116 EARS2 Danielle Ariti gene: EARS2 was added
gene: EARS2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: EARS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: EARS2 were set to 33528536; 34364746
Phenotypes for gene: EARS2 were set to Cerebral Palsy; Combined oxidative phosphorylation deficiency 12 MIM# 614924
Review for gene: EARS2 was set to GREEN
Added comment: Two individuals in CP cohort reported with bi-allelic EARS2 variants.
One of the individuals presented with severe ID, ASD and seizures on top of impaired motor symptoms.

Overlapping CP phenotype with COXPD12- mitochondrial neurologic disorder characterised by onset in infancy of hypotonia and delayed psychomotor development, or early developmental regression. Severe cases can present with Dystonia, Spastic tetraparesis and/or lack of speech.
Sources: Expert list
Cerebral Palsy v0.114 DDX3X Danielle Ariti gene: DDX3X was added
gene: DDX3X was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: DDX3X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: DDX3X were set to 33528536
Phenotypes for gene: DDX3X were set to Cerebral Palsy; Intellectual developmental disorder, X-linked, syndrome, Snijders Blok type MIM# 300958
Review for gene: DDX3X was set to GREEN
Added comment: 6 individuals in CP cohort reported with de novo DDX3X variants.
Sources: Expert list
Cerebral Palsy v0.114 DDHD2 Danielle Ariti gene: DDHD2 was added
gene: DDHD2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: DDHD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDHD2 were set to 30705080; 34077496; 34321325
Phenotypes for gene: DDHD2 were set to Cerebral Palsy; Spastic paraplegia 54, autosomal recessive MIM# 615033
Review for gene: DDHD2 was set to GREEN
Added comment: Two individuals reported in CP cohort. Phenotype-Spastic diplegia, and ID.

Multiple reports of CP-mimic patients with global developmental delay and non-progressive spastic gait.

SPG54 individuals display CP-like phenotype such as intellectual disability, early-onset spasticity of the lower limbs and delayed psychomotor development.
Sources: Expert list
Cerebral Palsy v0.114 DDC Zornitza Stark Added comment: Comment when marking as ready: Phenotypic overlap with CP: ID and movement disorders
Cerebral Palsy v0.111 DDC Danielle Ariti gene: DDC was added
gene: DDC was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: DDC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DDC were set to 33528536; 30799092; 33996177
Phenotypes for gene: DDC were set to Aromatic L-amino acid decarboxylase deficiency MIM# 608643
Review for gene: DDC was set to AMBER
Added comment: Single case reported in CP cohort with Dystonic cerebral palsy.

Multiple AADCD cases reported as CP- mimics due to phenotype overlap: dystonia and developmental delay.

AADCD being is an inborn error in neurotransmitter metabolism disorder that leads to combined serotonin and catecholamine deficiency. Clinically characterised by vegetative symptoms, oculogyric crises, dystonia, and severe neurologic dysfunction (infancy/ early childhood); displays CP-like features.
Sources: Expert list
Cerebral Palsy v0.111 COL4A2 Danielle Ariti gene: COL4A2 was added
gene: COL4A2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: COL4A2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COL4A2 were set to 33528536; 33912663
Phenotypes for gene: COL4A2 were set to Cerebral Palsy; Brain small vessel disease 2 MIM# 614483
Review for gene: COL4A2 was set to GREEN
Added comment: 7 individuals in CP cohort have been reported with mono-allelic COL4A2 variants. Phenotypic overlap: Spastic Triplegia, ID (no language), porencephaly and seizures.

2 siblings reported with bi-allelic variants; Spastic Cerebral Palsy with ID and Epilepsy.
Sources: Expert list
Cerebral Palsy v0.101 NALCN Zornitza Stark Phenotypes for gene: NALCN were changed from Cerebral palsy to Cerebral palsy; Congenital contractures of the limbs and face, hypotonia, and developmental delay (OMIM 616266)
Cerebral Palsy v0.99 ATL1 Clare van Eyk reviewed gene: ATL1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 33528536, PMID: 34321325; Phenotypes: Spastic paraplegia 3A, autosomal dominant (OMIM 182600 ); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.99 NALCN Clare van Eyk edited their review of gene: NALCN: Changed phenotypes: Congenital contractures of the limbs and face, hypotonia, and developmental delay (OMIM 616266)
Cerebral Palsy v0.99 NDUFA12 Clare van Eyk Deleted their comment
Cerebral Palsy v0.99 NDUFA12 Clare van Eyk edited their review of gene: NDUFA12: Added comment: Mitochondrial disorder causing motor dysfunction with learning difficulties (OMIM 618244). One case in cerebral palsy cohort.; Changed phenotypes: Mitochondrial complex I deficiency, nuclear type 23 (OMIM 618244)
Cerebral Palsy v0.99 NEXMIF Clare van Eyk Deleted their comment
Cerebral Palsy v0.99 NEXMIF Clare van Eyk edited their review of gene: NEXMIF: Added comment: Variants cause X-linked intellectual disability 98 (OMIM:300912). Developmental and epileptic encephalopathy with some affected individuals having movement phenotypes which could be considered CP-like, but did not find any published reports in CP cohorts to date.; Changed phenotypes: X-linked intellectual disability 98 (OMIM:300912)
Cerebral Palsy v0.99 PANK2 Clare van Eyk gene: PANK2 was added
gene: PANK2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PANK2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PANK2 were set to PMID: 33098801
Phenotypes for gene: PANK2 were set to HARP syndrome ( OMIM 607236); Neurodegeneration with brain iron accumulation 1 (OMIM 234200)
Review for gene: PANK2 was set to AMBER
Added comment: One case reported with dystonic cerebral palsy. Dystonia and spasticity are reported in cases with variants in PANK2.
Sources: Literature
Cerebral Palsy v0.99 NGLY1 Clare van Eyk gene: NGLY1 was added
gene: NGLY1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NGLY1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NGLY1 were set to PMID:33528536
Phenotypes for gene: NGLY1 were set to Congenital disorder of deglycosylation (OMIM 615273)
Review for gene: NGLY1 was set to GREEN
Added comment: Three cases with biallelic P/LP variants reported in Clinical Laboratory Referral Cohort retrospectively analysed for genetic determinants of cerebral palsy. Autosomal recessive, multisystem disorder with some overlapping clinical features with cerebral palsy, but this is a progressive condition.
Sources: Literature
Cerebral Palsy v0.99 NDUFAF2 Clare van Eyk reviewed gene: NDUFAF2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID:33528536, PMID:34364746; Phenotypes: mitochondrial complex I deficiency nuclear type 10 (OMIM 618233); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v0.99 NDUFAF2 Clare van Eyk Deleted their review
Cerebral Palsy v0.99 NEXMIF Clare van Eyk changed review comment from: Variants cause X-linked intellectual disability 98 (OMIM:300912). Developmental and epileptic encephalopathy with some affected individuals having movement phenotypes which could be considered CP-like, but did not find any reports in CP cohorts to date.
Sources: Expert list; to: Variants cause X-linked intellectual disability 98 (OMIM:300912). Developmental and epileptic encephalopathy with some affected individuals having movement phenotypes which could be considered CP-like, but did not find any published reports in CP cohorts to date.
Sources: Expert list
Cerebral Palsy v0.99 NEXMIF Clare van Eyk gene: NEXMIF was added
gene: NEXMIF was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: NEXMIF was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: NEXMIF were set to X-linked Intellectual disability; epilepsy; autism
Penetrance for gene: NEXMIF were set to Incomplete
Review for gene: NEXMIF was set to RED
Added comment: Variants cause X-linked intellectual disability 98 (OMIM:300912). Developmental and epileptic encephalopathy with some affected individuals having movement phenotypes which could be considered CP-like, but did not find any reports in CP cohorts to date.
Sources: Expert list
Cerebral Palsy v0.99 NDUFAF2 Clare van Eyk changed review comment from: Two homozygous pathogenic deletions reported in cerebral palsy cohorts. Biallelic loss of function variants cause mitochondrial complex I deficiency nuclear type 10 (OMIM 618233). Most variants are LOF. Overlapping clinical phenotype.
Sources: Literature; to: Two homozygous pathogenic deletions reported in cerebral palsy cohorts. Biallelic loss of function variants cause mitochondrial complex I deficiency nuclear type 10 (OMIM 618233). Overlapping clinical phenotype.
Sources: Literature
Cerebral Palsy v0.99 NDUFAF2 Clare van Eyk changed review comment from: Two homozygous pathogenic deletions reported in cerebral palsy cohorts. Biallelic loss of function variants cause mitochondrial complex I deficiency nuclear type 10 (OMIM 618233).
Sources: Literature; to: Two homozygous pathogenic deletions reported in cerebral palsy cohorts. Biallelic loss of function variants cause mitochondrial complex I deficiency nuclear type 10 (OMIM 618233). Most variants are LOF. Overlapping clinical phenotype.
Sources: Literature
Cerebral Palsy v0.99 NDUFAF2 Clare van Eyk gene: NDUFAF2 was added
gene: NDUFAF2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NDUFAF2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFAF2 were set to PMID:33528536; PMID:34364746
Phenotypes for gene: NDUFAF2 were set to Cerebral palsy
Review for gene: NDUFAF2 was set to GREEN
Added comment: Two homozygous pathogenic deletions reported in cerebral palsy cohorts. Biallelic loss of function variants cause mitochondrial complex I deficiency nuclear type 10 (OMIM 618233).
Sources: Literature
Cerebral Palsy v0.99 NDUFA12 Clare van Eyk gene: NDUFA12 was added
gene: NDUFA12 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NDUFA12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NDUFA12 were set to PMID:34364746
Phenotypes for gene: NDUFA12 were set to Spastic tetraparesis; intellectual disability; encephalopathy
Review for gene: NDUFA12 was set to AMBER
Added comment: Mitochondrial disorder causing motor dysfunction with learning difficulties (OMIM 618244). One case in cerebral palsy cohort.
Sources: Literature
Cerebral Palsy v0.99 NALCN Clare van Eyk reviewed gene: NALCN: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID:33528536, PMID:34364746; Phenotypes: Cerebral palsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.99 NALCN Clare van Eyk Deleted their review
Cerebral Palsy v0.99 NALCN Clare van Eyk gene: NALCN was added
gene: NALCN was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NALCN was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NALCN were set to PMID:33528536; 34364746
Phenotypes for gene: NALCN were set to Cerebral palsy
Review for gene: NALCN was set to AMBER
Added comment: One case with pathogenic variant from clinical laboratory referral cohort. One additional VUS from tertiary care setting. NALCN variants cause a congenital disorder with contractures of the limbs, abnormal facial features, hypotonia, and developmental delay (OMIM: 611549). Cerebral palsy has not been described previously.
Sources: Literature
Cerebral Palsy v0.99 CAMTA1 Zornitza Stark changed review comment from: Combination of ID with ataxia overlaps with CP.
Sources: Expert list; to: Combination of ID with ataxia overlaps with CP. At least 3 families reported, intragenic deletions.
Sources: Expert list
Cerebral Palsy v0.98 CAMTA1 Zornitza Stark gene: CAMTA1 was added
gene: CAMTA1 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: CAMTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CAMTA1 were set to 22693284; 24738973
Phenotypes for gene: CAMTA1 were set to Cerebellar ataxia, nonprogressive, with mental retardation, MIM# 614756
Review for gene: CAMTA1 was set to GREEN
Added comment: Combination of ID with ataxia overlaps with CP.
Sources: Expert list
Cerebral Palsy v0.96 CACNA1A Zornitza Stark gene: CACNA1A was added
gene: CACNA1A was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: CACNA1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CACNA1A were set to 29761117
Phenotypes for gene: CACNA1A were set to Developemental and epileptic encephalopathy 42, MIM# 617106; Episodic ataxia, type 2, MIM# 108500; Migraine, familial hemiplegic, 1, MIM# 141500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia 141500; Spinocerebellar ataxia 6, MIM# 183086
Review for gene: CACNA1A was set to AMBER
Added comment: Variants in this gene cause a range of phenotypes, including hemiplegia, although this tends to be episodic. Reported in a CP cohort.
Sources: Expert Review
Cerebral Palsy v0.95 BCL11A Zornitza Stark gene: BCL11A was added
gene: BCL11A was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: BCL11A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: BCL11A were set to Dias-Logan syndrome, MIM# 617101
Review for gene: BCL11A was set to RED
Added comment: Intellectual disability, microcephaly, dysmorphic features and persistence of fetal haemoglobin but no specific overlap with CP.
Sources: Expert Review
Cerebral Palsy v0.93 BCAP31 Zornitza Stark gene: BCAP31 was added
gene: BCAP31 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: BCAP31 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: BCAP31 were set to 24011989; 31330203
Phenotypes for gene: BCAP31 were set to Deafness, dystonia, and cerebral hypomyelination, MIM# 300475
Review for gene: BCAP31 was set to GREEN
Added comment: Phenotypic overlap with CP due to combination of almost no psychomotor development with dystonia and pyramidal signs. At least one patient reported who specifically had a CP diagnosis.
Sources: Expert Review
Cerebral Palsy v0.90 AUTS2 Zornitza Stark gene: AUTS2 was added
gene: AUTS2 was added to Cerebral Palsy. Sources: Expert list
SV/CNV tags were added to gene: AUTS2.
Mode of inheritance for gene: AUTS2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AUTS2 were set to 23332918; 27075013
Phenotypes for gene: AUTS2 were set to Mental retardation, autosomal dominant 26, MIM# 615834
Review for gene: AUTS2 was set to GREEN
Added comment: Multiple individuals reported with ID/autism, but 'cerebral palsy' was the original clinical diagnosis in some.

Predominantly deletions reported, so may not be tractable by all NGS assays.
Sources: Expert list
Cerebral Palsy v0.88 ATRX Zornitza Stark gene: ATRX was added
gene: ATRX was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ATRX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ATRX were set to Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580
Review for gene: ATRX was set to GREEN
Added comment: ID and hypotonia/hypertonia/spasticity: phenotypic overlap with CP. Well established gene-disease association.
Sources: Expert Review
Cerebral Palsy v0.87 ATP1A3 Zornitza Stark edited their review of gene: ATP1A3: Changed rating: RED
Cerebral Palsy v0.86 ATP1A3 Zornitza Stark gene: ATP1A3 was added
gene: ATP1A3 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ATP1A3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATP1A3 were set to Alternating hemiplegia of childhood 2, MIM# 614820; CAPOS syndrome, MIM# 601338; Dystonia-12, MIM# 128235
Review for gene: ATP1A3 was set to GREEN
Added comment: The disorders associated with variants in this gene tend to have episodic symptoms, insufficient overlap with CP.
Sources: Expert Review
Cerebral Palsy v0.85 ASXL3 Zornitza Stark gene: ASXL3 was added
gene: ASXL3 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ASXL3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ASXL3 were set to Bainbridge-Ropers syndrome, MIM# 615485
Review for gene: ASXL3 was set to RED
Added comment: Severe neurodevelopmental disorder but no strong overlap with CP.
Sources: Expert Review
Cerebral Palsy v0.83 ARX Zornitza Stark gene: ARX was added
gene: ARX was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ARX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ARX were set to Developmental and epileptic encephalopathy 1, MIM# 308350; Lissencephaly, X-linked 2, MIM# 300215; Proud syndrome, MIM# 300004
Review for gene: ARX was set to GREEN
Added comment: Well established gene-disease association. Phenotypic overlap: ID/seizures/abnormal tone.
Sources: Expert Review
Cerebral Palsy v0.79 ALS2 Zornitza Stark gene: ALS2 was added
gene: ALS2 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: ALS2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALS2 were set to 12145748; 33409823; 30128655
Phenotypes for gene: ALS2 were set to Spastic paralysis, infantile onset ascending, MIM# 607225
Review for gene: ALS2 was set to GREEN
Added comment: Well established gene-disease association. Phenotypic overlap with CP.
Sources: Expert Review
Cerebral Palsy v0.77 ALDH3A2 Zornitza Stark gene: ALDH3A2 was added
gene: ALDH3A2 was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: ALDH3A2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALDH3A2 were set to 9027499; 9829906; 28543186
Phenotypes for gene: ALDH3A2 were set to Sjogren-Larsson syndrome, MIM# 270200
Review for gene: ALDH3A2 was set to GREEN
Added comment: Well established gene-disease association. Phenotypic overlap with CP: ID and spastic paraplegia.
Sources: Expert list
Cerebral Palsy v0.74 ADAR Zornitza Stark gene: ADAR was added
gene: ADAR was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ADAR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ADAR were set to 33528536
Phenotypes for gene: ADAR were set to Aicardi-Goutieres syndrome 6, MIM# 615010
Review for gene: ADAR was set to GREEN
Added comment: Multiple individuals reported with CP-like phenotype in a cohort study.
Sources: Literature
Cerebral Palsy v0.71 HPDL Zornitza Stark gene: HPDL was added
gene: HPDL was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: HPDL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HPDL were set to 33634263
Phenotypes for gene: HPDL were set to Neurodevelopmental disorder with progressive spasticity and brain white matter abnormalities, MIM# 619026; Spastic paraplegia 83, autosomal recessive, MIM# 619027
Review for gene: HPDL was set to AMBER
Added comment: Overlapping phenotype, one family reported with cerebral palsy diagnosis and bi-allelic variants in this gene.
Sources: Literature
Cerebral Palsy v0.69 NKX2-1 Zornitza Stark Phenotypes for gene: NKX2-1 were changed from to Choreoathetosis, hypothyroidism, and neonatal respiratory distress, MIM# 610978
Cerebral Palsy v0.66 NKX2-1 Zornitza Stark reviewed gene: NKX2-1: Rating: GREEN; Mode of pathogenicity: None; Publications: 23911641, 11854319, 24714694; Phenotypes: Choreoathetosis, hypothyroidism, and neonatal respiratory distress, MIM# 610978; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.63 AP4S1 Zornitza Stark reviewed gene: AP4S1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27444738, 24065543; Phenotypes: Spastic paraplegia 52, autosomal recessive, MIM# 614067; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v0.60 AP4M1 Zornitza Stark reviewed gene: AP4M1: Rating: GREEN; Mode of pathogenicity: None; Publications: 19559397, 24065543, 25496299; Phenotypes: Spastic paraplegia 50, autosomal recessive, MIM# 612936; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v0.59 FBXO31 Zornitza Stark reviewed gene: FBXO31: Rating: GREEN; Mode of pathogenicity: None; Publications: 33675180; Phenotypes: Spastic-dystonic cerebral palsy; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.57 KDM5C Zornitza Stark Mode of inheritance for gene: KDM5C was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v0.56 KDM5C Zornitza Stark reviewed gene: KDM5C: Rating: GREEN; Mode of pathogenicity: None; Publications: 15586325, 32279304; Phenotypes: Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534, MONDO:0010355; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Cerebral Palsy v0.55 MINPP1 Zornitza Stark gene: MINPP1 was added
gene: MINPP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MINPP1 were set to 33257696
Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia
Review for gene: MINPP1 was set to GREEN
Added comment: 8 individuals from 6 unrelated families reported with bi-allelic LOF variants. All presented with almost complete absence of motor and cognitive development, progressive or congenital microcephaly, spastic tetraplegia or dystonia, and vision impairments. For most, the first symptoms included neonatal severe axial hypotonia and epilepsy that started during the first months or years of life. Prenatal symptoms of microcephaly associated with increased thalami echogenicity were detected in one, while the seven other individuals presented with progressive microcephaly. Some exhibited rapidly progressive phenotype and the affected children died in their infancy or middle-childhood. Strikingly, all the affected children had a unique brain MRI showing a mild to severe PCH, fluid-filled posterior fossa, with dilated lateral ventricles. In addition, severe atrophy at the level of the basal ganglia or thalami often associated with typical T2 hypersignal were identified in all the patients MRI.

Supportive functional data showing accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions.
Sources: Literature
Cerebral Palsy v0.53 TUBA1A Zornitza Stark reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Lissencephaly 3, MIM# 611603; Mode of inheritance: None
Cerebral Palsy v0.53 SPAST Zornitza Stark Added comment: Comment when marking as ready: Gene-disease association with spasticity is well established, individuals identified in a CP cohort.
Cerebral Palsy v0.51 FBXO31 Kristin Rigbye changed review comment from: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.

Extended patient phenotypes: Esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus (patient 1); Ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation (patient 2).

Sources: Literature; to: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.

Extended patient phenotypes: Spastic diplegia, with esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus (patient 1); Spastic paraplegia with ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation (patient 2).

Sources: Literature
Cerebral Palsy v0.51 FBXO31 Kristin Rigbye changed review comment from: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.
Sources: Literature; to: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.

Extended patient phenotypes: Esotropia, ID, dysarthria, mixed receptive/expressive language disorder, ADHD, cleft palate, intestinal malrotation and midgut volvulus (patient 1); Ventricular dilation and thin corpus callosum, ID, attention deficit, anxiety, language impairments, strabismus, severe constipation (patient 2).

Sources: Literature
Cerebral Palsy v0.51 SPAST Crystle Lee gene: SPAST was added
gene: SPAST was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: SPAST was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: SPAST were set to 32989326
Phenotypes for gene: SPAST were set to Cerebral Palsy (PMID:32989326)
Review for gene: SPAST was set to AMBER
Added comment: 2 different de novo missense variants reported in CP cohort. Both patients presented with spasticity.
Sources: Expert list
Cerebral Palsy v0.50 DHX32 Dean Phelan gene: DHX32 was added
gene: DHX32 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: DHX32 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: DHX32 were set to PMID: 32989326
Phenotypes for gene: DHX32 were set to Intellectual disability, spastic diplegia, dystonia, brain abnormalities
Review for gene: DHX32 was set to AMBER
Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two unrelated patients with intellectual disability, one with spastic diplegia, and the other characterised as generalised dystonia. Brain abnormalities were identified also.
Sources: Literature
Cerebral Palsy v0.44 ATL1 Kristin Rigbye gene: ATL1 was added
gene: ATL1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ATL1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATL1 were set to PMID: 32989326
Phenotypes for gene: ATL1 were set to Cerebral palsy
Review for gene: ATL1 was set to AMBER
Added comment: Two CP cohort patients with de novo ATL1 missense variants (p.Ala350Val and p.Lys406Gln) located in the GBP domain. Patients exhibited spasticity and dystonia with brain findings of T2 hyperintensities and bihemispheric periventricular leukomalacia. No functional studies.
Sources: Literature
Cerebral Palsy v0.43 FBXO31 Kristin Rigbye gene: FBXO31 was added
gene: FBXO31 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: FBXO31 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: FBXO31 were set to PMID: 32989326
Phenotypes for gene: FBXO31 were set to Cerebral palsy
Penetrance for gene: FBXO31 were set to unknown
Mode of pathogenicity for gene: FBXO31 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Review for gene: FBXO31 was set to AMBER
Added comment: 2 unrelated probands with CP harbouring the same de novo missense variant (p.Asp334Asn). The variant affects the cyclin D interaction site, leading to an apparent gain of function of cyclin D degradation, supported by Western blots from patient fibroblasts which showed decreased cyclin D expression.
Sources: Literature
Cerebral Palsy v0.43 ALK Dean Phelan gene: ALK was added
gene: ALK was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: ALK was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ALK were set to PMID: 32989326
Phenotypes for gene: ALK were set to Spastic-dystonic diplegia
Review for gene: ALK was set to AMBER
Added comment: PMID: 32989326 - Large cohort study of cerebral palsy cases identified two de novo variants in two patients with spastic diplegia with mild tremor, scattered subcortical hyperintensities and an atrial septal defect; and spastic-dystonic diplegia, white matter abnormalities and epilepsy, respectively, with no evidence of neuroblastoma in either patient.
Sources: Literature
Cerebral Palsy v0.43 RHOB Crystle Lee gene: RHOB was added
gene: RHOB was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: RHOB was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: RHOB were set to 32989326
Phenotypes for gene: RHOB were set to Cerebral Palsy (PMID:32989326)
Mode of pathogenicity for gene: RHOB was set to Other
Review for gene: RHOB was set to AMBER
Added comment: Candidate disease-causing gene for CP. Recurrent de novo missense variant reported in 2 unrelated families with supporting functional studies.
Sources: Expert Review
Cerebral Palsy v0.43 TUBA1A Crystle Lee reviewed gene: TUBA1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 32989326, 25666757; Phenotypes: Cerebral Palsy (PMID:32989326); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Cerebral Palsy v0.41 AGAP1 Zornitza Stark gene: AGAP1 was added
gene: AGAP1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: AGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: AGAP1 were set to 31700678; 25666757; 30472483
Phenotypes for gene: AGAP1 were set to Cerebral palsy
Review for gene: AGAP1 was set to AMBER
Added comment: Two individuals reported with de novo variants in this gene and a CP phenotype. Rare variants over-represented in a case-control study. Supportive zebrafish model. Another individual with a deletion (+1 other gene) reported with ID and autism.
Sources: Literature
Cerebral Palsy v0.38 L1CAM Zornitza Stark reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 31700678; Phenotypes: CRASH syndrome, MIM# 303350; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Cerebral Palsy v0.37 NT5C2 Zornitza Stark gene: NT5C2 was added
gene: NT5C2 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: NT5C2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NT5C2 were set to 31700678; 32153630
Phenotypes for gene: NT5C2 were set to Spastic paraplegia 45, autosomal recessive, MIM# 613162
Review for gene: NT5C2 was set to GREEN
Added comment: Overlapping phenotype, two families reported with a CP phenotype.
Sources: Literature
Cerebral Palsy v0.33 PROC Zornitza Stark gene: PROC was added
gene: PROC was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: PROC was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PROC were set to 31700678; 20187890
Phenotypes for gene: PROC were set to Thrombophilia due to protein C deficiency, autosomal recessive, MIM# 612304
Review for gene: PROC was set to AMBER
Added comment: Bi-allelic PROC variants described in 2 families presenting as complex CP. Other features such as purpura fulminans may be present depending on severity.
Sources: Literature
Cerebral Palsy v0.31 COL4A1 Zornitza Stark gene: COL4A1 was added
gene: COL4A1 was added to Cerebral Palsy. Sources: Literature
Mode of inheritance for gene: COL4A1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: COL4A1 were set to 31700678; 17379824
Phenotypes for gene: COL4A1 were set to {Hemorrhage, intracerebral, susceptibility to}, MIM# 614519
Review for gene: COL4A1 was set to AMBER
Added comment: One individual reported with variant in this gene and a CP phenotype PMID 31700678, and another with recurrent stroke PMID 17379824. However, note variable expressivity and penetrance generally associated with COL4A1 variants, and apply caution.
Sources: Literature
Cerebral Palsy v0.27 VPS13D Zornitza Stark reviewed gene: VPS13D: Rating: GREEN; Mode of pathogenicity: None; Publications: 29604224, 29518281; Phenotypes: Spinocerebellar ataxia, autosomal recessive 4, MIM# 607317; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v0.24 PCYT2 Zornitza Stark reviewed gene: PCYT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31637422; Phenotypes: Spastic paraplegia 82, autosomal recessive 618770; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v0.21 AP4E1 Zornitza Stark reviewed gene: AP4E1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20972249, 21620353, 21937992; Phenotypes: Spastic paraplegia 51, autosomal recessive, MIM# 613744; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v0.18 AP4B1 Zornitza Stark reviewed gene: AP4B1: Rating: GREEN; Mode of pathogenicity: None; Publications: 21620353, 22290197, 24700674, 24781758; Phenotypes: Spastic paraplegia 47, autosomal recessive, MIM# 614066; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v0.13 TNR Zornitza Stark gene: TNR was added
gene: TNR was added to Cerebral Palsy. Sources: Expert list
Mode of inheritance for gene: TNR was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TNR were set to 32099069
Phenotypes for gene: TNR were set to Spastic para- or tetraparesis; Axial muscular hypotonia; Intellectual disability; Transient opisthotonus
Review for gene: TNR was set to GREEN
Added comment: 13 individuals from 8 unrelated families reported.
Sources: Expert list
Cerebral Palsy v0.11 CTNNB1 Zornitza Stark gene: CTNNB1 was added
gene: CTNNB1 was added to Cerebral Palsy. Sources: Expert Review
Mode of inheritance for gene: CTNNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: CTNNB1 were set to Neurodevelopmental disorder with spastic diplegia and visual defects , MIM#615075
Review for gene: CTNNB1 was set to GREEN
Added comment: Sources: Expert Review
Cerebral Palsy v0.5 KANK1 Zornitza Stark reviewed gene: KANK1: Rating: RED; Mode of pathogenicity: None; Publications: 29729439, 30684669, 16301218; Phenotypes: Cerebral palsy, spastic quadriplegic, 2, MIM#612900; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Cerebral Palsy v0.1 GAD1 Zornitza Stark reviewed gene: GAD1: Rating: RED; Mode of pathogenicity: None; Publications: 15571623; Phenotypes: Cerebral palsy, spastic quadriplegic, 1, MIM#603513; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Cerebral Palsy v0.0 TENM1 Zornitza Stark reviewed gene: TENM1: Rating: RED; Mode of pathogenicity: None; Publications: 25666757; Phenotypes: ; Mode of inheritance: None