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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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. |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 | 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 |
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| 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 |
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| 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 | 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 |
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| 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 |
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| 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 |
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| 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 v1.294 | 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 | 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 |
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| 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 | 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 |
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| 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 v1.193 | 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 |
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| 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 | 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 | 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 |
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| 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 |
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| 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 |
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| 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 v1.189 | DHX32 | Zornitza Stark Phenotypes for gene: DHX32 were changed from Intellectual disability, spastic diplegia, dystonia, brain abnormalities to Neurodevelopmental disorder, MONDO:0700092, DHX32-related | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
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| 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 |
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| 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 |
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| 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 v1.174 | 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 v1.146 | 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| Cerebral Palsy v1.135 | PNPLA6 | Zornitza Stark Phenotypes for gene: PNPLA6 were changed from Boucher-Neuhauser syndrome MIM#215470; Oliver-McFarlane syndrome MIM#275400; Spastic paraplegia 39 MIM#612020 to Spastic paraplegia 39 MIM#612020 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
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| 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 |
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| 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 |
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| Cerebral Palsy v1.132 | PLP1 | Zornitza Stark Phenotypes for gene: PLP1 were changed from Pelizaeus-Merzbacher disease MIM#312080; Spastic paraplegia 2, X-linked MIM#312920 to Spastic paraplegia 2, X-linked MIM#312920 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 | 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 v0.140 | 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| Cerebral Palsy v0.111 | CYP2U1 |
Danielle Ariti changed review comment from: Single case reported in CP cohort (bi-allelic c.A947T variant). SPG56 is an autosomal recessive neurodegenerative disorder characterised by early-onset progressive lower-limb spasticity. 4 reported SPG56 cases display CP-like phenotype: ID and spastic diplegia. Sources: Expert list; to: Single case reported in CP cohort (bi-allelic p.D316V variant). SPG56 is an autosomal recessive neurodegenerative disorder characterised by early-onset progressive lower-limb spasticity. 4 reported SPG56 cases display CP-like phenotype: ID and spastic diplegia. Sources: Expert list |
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| Cerebral Palsy v0.111 | CYP2U1 |
Danielle Ariti gene: CYP2U1 was added gene: CYP2U1 was added to Cerebral Palsy. Sources: Expert list Mode of inheritance for gene: CYP2U1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CYP2U1 were set to 33528536; 29761117; 23176821 Phenotypes for gene: CYP2U1 were set to Cerebral Palsy; Spastic paraplegia 56, autosomal recessive MIM# 615030 Review for gene: CYP2U1 was set to GREEN Added comment: Single case reported in CP cohort (bi-allelic c.A947T variant). SPG56 is an autosomal recessive neurodegenerative disorder characterised by early-onset progressive lower-limb spasticity. 4 reported SPG56 cases display CP-like phenotype: ID and spastic diplegia. Sources: Expert list |
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| 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 |
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| Cerebral Palsy v0.111 | ATL1 | Zornitza Stark Phenotypes for gene: ATL1 were changed from Cerebral palsy; Spastic paraplegia 3A, autosomal dominant (OMIM 182600 ) to Cerebral palsy; Spastic paraplegia 3A, autosomal dominant (OMIM 182600 ) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.111 | ATL1 | Zornitza Stark Phenotypes for gene: ATL1 were changed from Cerebral palsy to Cerebral palsy; Spastic paraplegia 3A, autosomal dominant (OMIM 182600 ) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | 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 |
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| 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 |
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| 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 |
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| Cerebral Palsy v0.81 | AMPD2 |
Zornitza Stark gene: AMPD2 was added gene: AMPD2 was added to Cerebral Palsy. Sources: Expert Review Mode of inheritance for gene: AMPD2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: AMPD2 were set to 23911318; 27066553; 29761117 Phenotypes for gene: AMPD2 were set to Pontocerebellar hypoplasia, type 9, MIM# 615809 Review for gene: AMPD2 was set to GREEN Added comment: Well established gene-disease association. Phenotypic overlap: ID and spastic paraplegia. Reported in CP cohort. Sources: Expert Review |
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| 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 |
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| 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 |
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| 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 |
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| Cerebral Palsy v0.66 | AP4S1 | Zornitza Stark Phenotypes for gene: AP4S1 were changed from to Spastic paraplegia 52, autosomal recessive, MIM# 614067 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.63 | AP4M1 | Zornitza Stark Phenotypes for gene: AP4M1 were changed from to Spastic paraplegia 50, autosomal recessive, MIM# 612936 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.55 | 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 |
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| Cerebral Palsy v0.53 | SPAST | Zornitza Stark Marked gene: SPAST as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.53 | SPAST | Zornitza Stark Gene: spast has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.53 | SPAST | Zornitza Stark Classified gene: SPAST as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.53 | SPAST | Zornitza Stark Gene: spast has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| 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 |
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| Cerebral Palsy v0.35 | KIF1A |
Zornitza Stark gene: KIF1A was added gene: KIF1A was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: KIF1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KIF1A were set to 31700678 Phenotypes for gene: KIF1A were set to Spastic paraplegia 30, autosomal dominant, MIM# 610357 Review for gene: KIF1A was set to GREEN Added comment: Overlapping phenotype and at least two individuals identified as part of a CP cohort. Sources: Literature |
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| Cerebral Palsy v0.27 | PCYT2 | Zornitza Stark Phenotypes for gene: PCYT2 were changed from to Spastic paraplegia 82, autosomal recessive 618770 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.24 | AP4E1 | Zornitza Stark Phenotypes for gene: AP4E1 were changed from to Spastic paraplegia 51, autosomal recessive, MIM# 613744 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.21 | AP4B1 | Zornitza Stark Phenotypes for gene: AP4B1 were changed from to Spastic paraplegia 47, autosomal recessive, MIM# 614066 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.17 | ADD3 |
Zornitza Stark gene: ADD3 was added gene: ADD3 was added to Cerebral Palsy. Sources: Expert Review Mode of inheritance for gene: ADD3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ADD3 were set to 23836506; 29768408 Phenotypes for gene: ADD3 were set to Cerebral palsy, spastic quadriplegic, 3 617008 Review for gene: ADD3 was set to GREEN Added comment: Four families reported. Sources: Expert Review |
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| Cerebral Palsy v0.15 | GSX2 |
Zornitza Stark gene: GSX2 was added gene: GSX2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: GSX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GSX2 were set to 31412107 Phenotypes for gene: GSX2 were set to Diencephalic-mesencephalic junction dysplasia syndrome 2 618646; Intellectual disability; Dystonia; Spastic tetra paresis Review for gene: GSX2 was set to AMBER Added comment: Two unrelated families, some functional data. Sources: Literature |
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| 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 |
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| 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 |
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| Cerebral Palsy v0.8 | KANK1 | Zornitza Stark Phenotypes for gene: KANK1 were changed from to Cerebral palsy, spastic quadriplegic, 2, MIM#612900 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 v0.5 | GAD1 | Zornitza Stark Phenotypes for gene: GAD1 were changed from to Cerebral palsy, spastic quadriplegic, 1, MIM#603513 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||