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Fetal anomalies v1.311 ITGAV Zornitza Stark gene: ITGAV was added
gene: ITGAV was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ITGAV was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ITGAV were set to 39526957
Phenotypes for gene: ITGAV were set to Syndromic disease, MONDO:0002254, ITGAV-related
Review for gene: ITGAV was set to AMBER
Added comment: Three unrelated families reported: two with affected children (one hmz missense; other compound het LoF with missense) and one family with four affected fetuses. Clinical features included brain and eye anomalies and IBD/immune dysregulation. TGF-beta signalling pathway affected. The deletion of itgav in zebrafish recapitulated patient phenotypes including retinal and brain defects and the loss of microglia in early development as well as colitis in juvenile zebrafish with reduced SMAD3 expression and transcriptional regulation.
Sources: Literature
Fetal anomalies v1.300 PDE12 Zornitza Stark gene: PDE12 was added
gene: PDE12 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PDE12 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PDE12 were set to 39567835
Phenotypes for gene: PDE12 were set to Mitochondrial disease MONDO:0044970, PDE12-related
Review for gene: PDE12 was set to GREEN
Added comment: 3 families (2 consanguineous) with 5 affected individuals with early onset mitochondrial disease presentation (3 liveborn, 2 intrauterine death).
-Family 1: 1 x infant death @3mths (no clinical information), 1 x 7yr old with neonatal respiratory and lactic acidosis, developmental delay, and mitochondrial respiratory chain deficiencies, and marked cytochrome c oxidase (COX) deficiency in muscle.
-Family 2: 1 x neonatal death @2days with metabolic acidosis and lactic acidosis, respiratory failure, lissencephaly, dysgenesis of the corpus callosum and extensive periventricular and subcortical cysts. Normal pyruvate dehydrogenase complex and electron
transfer chain activities in fibroblasts.
-Family 3: 2 x fetuses (13wks and 22wks) with increase nuchal translucency and reduced fetal movements. One had intra-uterine growth retardation, hydrops and cystic hygroma. The other had permanent flexion contractures of four limbs). Western blotting in fetal skeletal muscle showed absent respiratory chain complexes (I, IV, and V).

WES in all 3 families identified 3 different homozygous missense variants in PDE12 gene (p.Tyr155Cys, p.Gly372Glu, and p.Arg41Pro). All variants segregated with disease, were rare in gnomAD, and in silico pathogenicity prediction tools pointed towards a high likelihood of pathogenicity.

PDE12 gene encodes the poly(A)-specific exoribonuclease, involved in the quality control of mitochondrial non-coding RNAs. Patient-derived primary fibroblasts demonstrate diminished steady-state levels of PDE12 protein, whilst mitochondrial poly(A)-tail RNA sequencing revealed an accumulation of spuriously polyadenylated mitochondrial RNA, consistent with perturbed function of PDE12 protein.
Sources: Literature
Fetal anomalies v1.282 FLVCR1 Zornitza Stark Phenotypes for gene: FLVCR1 were changed from Ataxia, posterior column, with retinitis pigmentosa, MIM#609033 to neurodevelopmental disorder MONDO:0700092, FLVCR1-related; Ataxia, posterior column, with retinitis pigmentosa, MIM#609033
Fetal anomalies v1.279 FLVCR1 Zornitza Stark edited their review of gene: FLVCR1: Added comment: PMID 39306721: A new study with 30 patients from 23 unrelated families with biallelic ultra-rare missense and predicted loss-of-function variants in FLVCR1 with a novel FLVCR1-related phenotype characterised by severe developmental disorders with profound developmental delay, microcephaly, brain malformations, epilepsy, spasticity, and premature death. Optic disk atrophy, limb and digital malformations, and macrocytic anaemia can be present.

Included here as brain, limb and digital malformations can present antenatally.; Changed rating: GREEN; Changed publications: 39306721; Changed phenotypes: neurodevelopmental disorder MONDO:0700092, FLVCR1-related, Ataxia, posterior column, with retinitis pigmentosa, MIM#609033
Fetal anomalies v1.274 GMPPA Ain Roesley Phenotypes for gene: GMPPA were changed from Alacrima, achalasia, and mental retardation syndrome (MIM# 615510) to Alacrima, achalasia, and impaired intellectual development syndrome (MIM# 615510)
Fetal anomalies v1.273 USP9X Ain Roesley Phenotypes for gene: USP9X were changed from Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968) to Intellectual developmental disorder 99 MIM#300919; syndromic, female-restricted Intellectual developmental disorder 99 MIM#300968
Fetal anomalies v1.271 PPP2R5D Ain Roesley Phenotypes for gene: PPP2R5D were changed from Mental retardation, autosomal dominant 35, MIM#616355 to Houge-Janssens syndrome 1, MIM#616355
Fetal anomalies v1.264 CSMD1 Krithika Murali gene: CSMD1 was added
gene: CSMD1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CSMD1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CSMD1 were set to PMID: 38816421
Phenotypes for gene: CSMD1 were set to complex neurodevelopmental disorder MONDO:0100038
Review for gene: CSMD1 was set to GREEN
Added comment: Prenatal features reported include polyhydramnios, IUGR, preterm labour. Other reported features such as brain anomalies, arthrogryposis have the potential to be ascertained prenatally also.
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PMID 38816421 Werren et al 2024 report 8 individuals from 6 families with biallelic missense CSMD1 variants identified through exome sequencing and subsequent gene-sharing efforts. Shared phenotypic features included: GDD, ID, microcephaly and polymicrogyria. Other features included dysmorphism, IUGR, hypotonia, arthrogryposis, seizures, opthalmological anomalies and other brain white matter anomalies Heterozygous parents were unaffected.

Loss of function is the postulated mechanism based on experimental data involving early-stage forebrain organoids differentiated from CSMD1 knockout human embryonic stem cells. ClinGen haploinsufficiency score of 1, however, this curation was last reviewed in 2018. This gene is within the scope of review for the ClinGen Autism and ID GCEP.
Sources: Literature
Fetal anomalies v1.234 KDM5C Ain Roesley Phenotypes for gene: KDM5C were changed from Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355 to Intellectual developmental disorder, X-linked syndromic, Claes-Jensen type MIM# 300534; MONDO:0010355
Fetal anomalies v1.232 PURA Ain Roesley Phenotypes for gene: PURA were changed from Mental retardation, autosomal dominant 31, MIM# 616158 to Neurodevelopmental disorder with neonatal respiratory insufficiency, hypotonia, and feeding difficulties (OMIM 616158)
Fetal anomalies v1.191 THOC2 Zornitza Stark Phenotypes for gene: THOC2 were changed from Mental retardation, X-linked 12/35 MIM#300957 to Mental retardation, X-linked 12/35 MIM#300957; Arthrogryposis (MONDO:0008779), THOC2-related
Fetal anomalies v1.189 THOC2 Zornitza Stark edited their review of gene: THOC2: Added comment: PMID: 34976470 - arthrogryposis multiplex congenita phenotype (AMC) in two male fetuses in a family, caused by splice deletion c.2482-1_2484delGTCA which was mat inherited. No splice studies conducted, mother was normal. Postulate that amorphic or severe null pathogenic variants (possible complete loss of function) lead to AMC phenotype

PMID: 37945483 - a proband with AMC and the same splice site mutation ^ above, but de novo. Cytoplasmic bodies also detected in muscle; Changed publications: 29851191, 34976470, 37945483; Changed phenotypes: Mental retardation, X-linked 12/35 MIM#300957, Arthrogryposis (MONDO:0008779), THOC2-related
Fetal anomalies v1.167 PKP2 Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.
Sources: Literature; to: PMID: 30562116: reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.
Sources: Literature
Fetal anomalies v1.167 PKP2 Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature; to: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consistent to Wolff Parkinson-White syndrome.
Sources: Literature
Fetal anomalies v1.167 PKP2 Suliman Khan changed review comment from: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In cases, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature; to: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In case 1, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case 2 had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature
Fetal anomalies v1.167 PKP2 Suliman Khan gene: PKP2 was added
gene: PKP2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PKP2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PKP2 were set to PMID: 30562116; PMID: 35059364; PMID: 38050058
Phenotypes for gene: PKP2 were set to dilated cardiomyopathy; hypoplastic left heart syndrome; hydrops fetalis; ventricular septal defect; left ventricular non-compaction
Penetrance for gene: PKP2 were set to unknown
Review for gene: PKP2 was set to GREEN
Added comment: PMID: 30562116: PMID: 30562116 reported 2 cases with hypoplastic left heart syndrome (HLHS) and features of noncompaction resulting from a homozygous truncating variant in the PKP2 gene (c.1211dup (p.Val406fsTer4). In the second pregnancy, additional features of fetal hydrops, HLHS, severe RVH, NC, multiple VSD were observed.
PMID: 35059364: reported a homozygous PKP2 variant, c.1511-1G>C, in an infant with neonatal onset of congestive heart failure owing to severe Left ventricular non-compaction (LVNC) and multiple muscular ventricular septal defect (VSD).
PMID: 38050058 reported biallelic loss of function variants in three cases with lethal form of dilated cardiomyopathy with excessive trabeculations (DCM-ET). In cases, additional symptoms reported were micrognathia, retrognathia and hypertelorism. Case had no extracardiac anomalies. In case 3, additional symptoms of hepatomegaly, supraventricular tachycardia consist to Wolff Parkinson-White syndrome.
Sources: Literature
Fetal anomalies v1.149 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from Alpha-thalassemia/mental retardation syndrome, MIM# 301040 to ATR-X-related syndrome MONDO:0016980
Fetal anomalies v1.132 PHF5A Daniel Flanagan gene: PHF5A was added
gene: PHF5A was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: PHF5A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: PHF5A were set to PMID: 37422718
Review for gene: PHF5A was set to GREEN
Added comment: Nine subjects with congenital malformations, including hypospadias, growth abnormalities, and developmental delay who had de novo PHF5A variants. Prenatally, six subjects had intrauterine growth retardation. All subjects had motor and speech delay and developmental delay. Congenital abnormalities comprised hypospadias in three of four male subjects and heart defects, inguinal hernia, and sacral dimple in three subjects. Six of the nine subjects had short stature. Craniofacial dysmorphism is variable in the nine subjects, high forehead and preauricular skin tag(s) in five subjects.
Sources: Expert list
Fetal anomalies v1.76 FRA10AC1 Zornitza Stark Phenotypes for gene: FRA10AC1 were changed from Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related to Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113
Fetal anomalies v1.75 FRA10AC1 Zornitza Stark reviewed gene: FRA10AC1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Neurodevelopmental disorder with growth retardation, dysmorphic facies, and corpus callosum abnormalities, MIM# 620113; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.69 USP9X Krithika Murali reviewed gene: USP9X: Rating: GREEN; Mode of pathogenicity: None; Publications: 31443933, 26833328; Phenotypes: Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968); Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Fetal anomalies v1.25 FTO Bryony Thompson reviewed gene: FTO: Rating: GREEN; Mode of pathogenicity: None; Publications: 19234441, 19559399, 26378117, 26697951, 26378117, 26740239; Phenotypes: Growth retardation, developmental delay, facial dysmorphism MIM#612938; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v1.19 CDK10 Ain Roesley gene: CDK10 was added
gene: CDK10 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CDK10 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CDK10 were set to 28886341; 34974531
Phenotypes for gene: CDK10 were set to Al Kaissi syndrome MIM#617694
Review for gene: CDK10 was set to GREEN
gene: CDK10 was marked as current diagnostic
Added comment: 6 families reported

1x with IUGR, 1x hydrocephalus and 1x with fetal hydrops, hydrocephalus, multicystic, dysplastic kidneys, lung hypoplasia, cardiomyopathy, retrognathia

Small birth weight/sizes reported in all
Sources: Literature
Fetal anomalies v1.17 RSPO2 Zornitza Stark gene: RSPO2 was added
gene: RSPO2 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: RSPO2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RSPO2 were set to 29769720; 32457899
Phenotypes for gene: RSPO2 were set to Tetraamelia syndrome 2, MIM# 618021
Review for gene: RSPO2 was set to GREEN
Added comment: Tetraamelia syndrome-2 (TETAMS2) is characterized by rudimentary appendages or complete absence of the limbs, usually symmetric, as well as bilateral agenesis of the lungs. There are abnormalities of the pulmonary vasculature and dysmorphic features, including bilateral cleft lip/palate, ankyloglossia, mandibular hypoplasia, microretrognathia, and labioscrotal fold aplasia. Four unrelated families and functional data including animal model.
Sources: Expert Review
Fetal anomalies v1.9 UNC80 Zornitza Stark Phenotypes for gene: UNC80 were changed from Persistent Hypotonia, Encephalopathy, Growth Retardation, and Severe Intellectual Disability to Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801; MONDO:0014777
Fetal anomalies v1.7 UNC80 Ain Roesley reviewed gene: UNC80: Rating: AMBER; Mode of pathogenicity: None; Publications: 26545877; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 2, MIM# 616801, MONDO:0014777; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.4702 CCDC28B Krithika Murali gene: CCDC28B was added
gene: CCDC28B was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: CCDC28B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CCDC28B were set to 32139166
Phenotypes for gene: CCDC28B were set to Joubert syndrome
Review for gene: CCDC28B was set to AMBER
Added comment: No new publications since last PanelApp review May 2020

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PMID: 32139166 - Single family with Joubert syndrome. Patient was homozygous for a missense, with polydactyly, severe ID, and the molar tooth sign observed in MRI. Sibling fetus MRI showed vermis hypoplasia, and was also homozygous for the variant. Parents confirmed unaffected carriers. Knockdown of CCDC28B in human TERT retinal pigment epithelial cells reduced both the number and length of cilia 430C-T variant is postulated to be a modifier of BBS.
Sources: Literature
Fetal anomalies v0.4699 NCAPD2 Zornitza Stark gene: NCAPD2 was added
gene: NCAPD2 was added to Fetal anomalies. Sources: Expert Review
Mode of inheritance for gene: NCAPD2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NCAPD2 were set to 31056748; 27737959; 28097321
Phenotypes for gene: NCAPD2 were set to Microcephaly 21, primary, autosomal recessive; OMIM #617983
Review for gene: NCAPD2 was set to GREEN
Added comment: Three families reported: 1 family with 2 sibs with microcephaly and ID, and homozygous NCAPD2 mutation, which segregated with disease. No functional evidence. 1 family with 1 affected and homozygous NCAPD2 mutation, which segregated with disease. Patient fibroblasts showed impaired chromosome segregation and abnormal recovery from mitotic condensation compared to controls. 1 family with 2 sibs with microcephaly, growth retardation, and ID, and homozygous NCAPD2 mutation, which segregated with disease. Functional studies of the variants and studies of patient cells were not performed.

IUGR reported.
Sources: Expert Review
Fetal anomalies v0.4618 POMGNT1 Zornitza Stark Phenotypes for gene: POMGNT1 were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C3; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B3; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A3 (MDDGA3 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3, 253280
Fetal anomalies v0.4602 PGAP2 Zornitza Stark Phenotypes for gene: PGAP2 were changed from INTELLECTUAL DISABILITY to Hyperphosphatasia with mental retardation syndrome 3, MIM# 614207, MONDO:0013628
Fetal anomalies v0.4600 PGAP3 Zornitza Stark Phenotypes for gene: PGAP3 were changed from HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 4 to Hyperphosphatasia with mental retardation syndrome 4, MIM# 615716, MONDO:0014318
Fetal anomalies v0.4596 PHF8 Zornitza Stark Phenotypes for gene: PHF8 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED SIDERIUS TYPE to Intellectual developmental disorder, X-linked, syndromic, Siderius type, MIM# 300263
Fetal anomalies v0.4581 PIGO Zornitza Stark Phenotypes for gene: PIGO were changed from HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 2 to Hyperphosphatasia with mental retardation syndrome 2, MIM# 614749, MONDO:0013882
Fetal anomalies v0.4577 PIGV Zornitza Stark Phenotypes for gene: PIGV were changed from HYPERPHOSPHATASIA WITH MENTAL RETARDATION to Hyperphosphatasia with mental retardation syndrome 1, MIM# 239300, MONDO:0009398
Fetal anomalies v0.4550 POMT1 Zornitza Stark Phenotypes for gene: POMT1 were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C1; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B1; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A1 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 1 236670; Walker-Walburg syndrome
Fetal anomalies v0.4548 POMT2 Zornitza Stark Phenotypes for gene: POMT2 were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A2; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B2; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C2 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 2 613150
Fetal anomalies v0.4542 PPP2R1A Zornitza Stark Phenotypes for gene: PPP2R1A were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 36, MIM#616362; Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome, MONDO:0014605
Fetal anomalies v0.4538 PPP2R5D Zornitza Stark Phenotypes for gene: PPP2R5D were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 35, MIM#616355
Fetal anomalies v0.4515 PRKAR1A Zornitza Stark changed review comment from: Multiple phenotypes associated with this gene, but this particular OMIM condition has ID as part of the phenotype.; to: Multiple phenotypes associated with this gene, but this particular OMIM condition has prenatal growth retardation as part of the phenotype.
Fetal anomalies v0.4505 RAC1 Zornitza Stark Phenotypes for gene: RAC1 were changed from Developmental Disorders with Diverse Phenotypes to Mental retardation, autosomal dominant 48, MIM# 617751
Fetal anomalies v0.4478 MCM7 Krithika Murali gene: MCM7 was added
gene: MCM7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MCM7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCM7 were set to 33654309; 34059554
Phenotypes for gene: MCM7 were set to Meier-Gorlin syndrome; Microcephaly; Intellectual disability; Lipodystrophy; Adrenal insufficiency
Review for gene: MCM7 was set to AMBER
Added comment: Association with congenital microcephaly. No new publications since last PanelApp review

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MCM7 is a component of the MCM complex, a DNA helicase which is essential for DNA replication. Other components have been linked to disease with phenotypes including microcephaly and ID. MCM7 is not associated with any phenotype in OMIM or G2P at present. ------ Currently there are 3 unrelated pedigrees in literature with different biallelic MCM7 variants associated with disease (see below). Although there is some functional data in support of variant-level deleteriousness or gene-level pathogenicity, the clinical gestalt is very different between the 3 families.

- PMID: 33654309 (2021) - Two unrelated individuals with different compound het variants in MCM7 but disparate clinical features. One patient had typical Meier-Gorlin syndrome (including growth retardation, microcephaly, congenital lung emphysema, absent breast development, microtia, facial dysmorphism) whereas the second case had a multi-system disorder with neonatal progeroid appearance, lipodystrophy and adrenal insufficiency. While small at birth, the second patient did not demonstrate reduced stature or microcephaly at age 14.5 years. Both individuals had normal neurodevelopment. Functional studies using patient-derived fibroblasts demonstrate that the identified MCM7 variants were deleterious at either transcript or protein levels and through interfering with MCM complex formation, impact efficiency of S phase progression.

- PMID: 34059554 (2021) - Homozygous missense variant identified in three affected individuals from a consanguineous family with severe primary microcephaly, severe ID and behavioural abnormalities. Knockdown of Mcm7 in mouse neuroblastoma cells lead to reduced cell viability and proliferation with increased apoptosis, which were rescued by overexpression of wild-type but not mutant MCM7.
Sources: Literature
Fetal anomalies v0.4478 LINGO1 Krithika Murali gene: LINGO1 was added
gene: LINGO1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LINGO1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LINGO1 were set to 28837161; 31668702
Phenotypes for gene: LINGO1 were set to Mental retardation, autosomal recessive 64 - MIM#618103
Review for gene: LINGO1 was set to AMBER
Added comment: 5 individuals reported from 2 families. 4 out of the 5 individuals had microcephaly. ID, developmentatl delay, spasticity, hypertonia, feeding problems also reported features. No antenatal information or birth growth parameters provided, but it is possible that microcephaly was antenatal/congenital in onset based on other phenotypic features reported.
Sources: Literature
Fetal anomalies v0.4463 RET Zornitza Stark Marked gene: RET as ready
Fetal anomalies v0.4463 RET Zornitza Stark Gene: ret has been classified as Green List (High Evidence).
Fetal anomalies v0.4463 RET Zornitza Stark Phenotypes for gene: RET were changed from RENAL AGENESIS; MULTIPLE ENDOCRINE NEOPLASIA IIB to Central hypoventilation syndrome, congenital, MIM#209880; Multiple endocrine neoplasia IIA, MIM#171400; Multiple endocrine neoplasia IIB, MIM#162300
Fetal anomalies v0.4462 RET Zornitza Stark Mode of inheritance for gene: RET was changed from BOTH monoallelic and biallelic, autosomal or pseudoautosomal to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4459 RET Zornitza Stark changed review comment from: ID is not part of the phenotype.; to: Megacolon is a feature.
Fetal anomalies v0.4459 RET Zornitza Stark edited their review of gene: RET: Changed rating: GREEN
Fetal anomalies v0.4402 SETD5 Zornitza Stark Phenotypes for gene: SETD5 were changed from MENTAL RETARDATION, AUTOSOMAL DOMINANT 23 to Intellectual disability, autosomal dominant 23 (MIM # 615761)
Fetal anomalies v0.4305 VPS50 Chirag Patel gene: VPS50 was added
gene: VPS50 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: VPS50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS50 were set to PMID: 34037727
Phenotypes for gene: VPS50 were set to Neurodevelopmental disorder with microcephaly, seizures, and neonatal cholestasis , MIM#619685
Review for gene: VPS50 was set to AMBER
Added comment: Schneeberger et al (2021 - PMID: 34037727) describe the phenotype of 2 unrelated individuals with biallelic VPS50 variants. Common features included transient neonatal cholestasis, failure to thrive, severe DD with failure to achieve milestones (last examination at 2y and 2y2m respectively), postnatal microcephaly, seizures (onset at 6m and 25m) and irritability. There was corpus callosum hypoplasia on brain imaging. Both individuals were homozygous for variants private to each family (no/not known consanguinity applying to each case). The first individual was homozygous for a splicing variant (NM_017667.4:c.1978-1G>T) and had a similarly unaffected sister deceased with no available DNA for testing. The other individual was homozygous for an in-frame deletion (c.1823_1825delCAA / p.(Thr608del)). VPS50 encodes a critical component of the endosome-associated recycling protein (EARP) complex, which functions in recycling endocytic vesicles back to the plasma membrane [OMIM based on Schindler et al]. The complex contains VPS50, VPS51, VPS52, VPS53, the three latter also being components of GARP (Golgi-associated-retrograde protein) complex. GARP contains VPS54 instead of VPS50 and is required for trafficking of proteins to the trans-golgi network. Thus VPS50 (also named syndetin) and VPS54 function in the EARP and GARP complexes, to define directional movement of their endocytic vesicles [OMIM based on Schindler et al]. The VPS50 subunit is required for recycling of the transferrin receptor. As discussed by Schneeberger et al (refs provided in text): - VPS50 has a high expression in mouse and human brain as well as throughout mouse brain development. - Mice deficient for Vps50 have not been reported. vps50 knockdown in zebrafish results in severe developmental defects of the body axis. Knockout mice for other proteins of the EARP/GARP complex (e.g. Vps52, 53 and 54) display embryonic lethality. Studies performed by Schneeberger et al included: - Transcript analysis for the 1st variant demonstrated skipping of ex21 (in patient derived fabriblasts) leading to an in frame deletion of 81 bp (r.1978_2058del) with predicted loss of 27 residues (p.Leu660_Leu686del). - Similar VPS50 mRNA levels but significant reduction of protein levels (~5% and ~8% of controls) were observed in fibroblasts from patients 1 and 2. Additionally, significant reductions in the amounts of VPS52 and VPS53 protein levels were observed despite mRNA levels similar to controls. Overall, this suggested drastic reduction of functional EARP complex levels. - Lysosomes appeared to have similar morphology, cellular distribution and likely unaffected function in patient fibroblasts. - Transferrin receptor recycling was shown to be delayed in patient fibroblasts suggestive of compromise of endocytic-recycling function. As the authors comment, the phenotype of both individuals with biallelic VPS50 variants overlaps with the corresponding phenotype reported in 15 subjects with biallelic VPS53 or VPS51 mutations notably, severe DD/ID, microcephaly and early onset epilepsy, CC anomalies. Overall, for this group, they propose the term "GARP and/or EARP deficiency disorders". There is no VPS50-associated phenotype in OMIM or G2P. SysID includes VPS50 among the ID candidate genes.
Sources: Expert list
Fetal anomalies v0.4299 WDR4 Chirag Patel gene: WDR4 was added
gene: WDR4 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: WDR4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: WDR4 were set to PubMed: 26416026; 28617965
Phenotypes for gene: WDR4 were set to Microcephaly, growth deficiency, seizures, and brain malformations, OMIM # 618346
Review for gene: WDR4 was set to GREEN
Added comment: Microcephaly, growth deficiency, seizures, and brain malformations (MIGSB) is a severe autosomal recessive disorder characterized by intrauterine growth retardation, postnatal growth deficiency with severe microcephaly, and poor or absent psychomotor development. Additional features include optic atrophy, early-onset seizures, dysmorphic facial features, and brain malformations, such as partial agenesis of the corpus callosum and simplified gyration.

Biallelic variants in the WDR4 gene reported in 4 patients from 3 unrelated families. Studies of patient cells in one family and modeling of the corresponding mutation in yeast showed that the mutation caused a significant reduction in m(7)G46 methylation of specific tRNAs species, particularly at higher temperatures. This was associated with a growth defect in yeast, thus offering a potential mechanism for the growth defects observed in patients with the mutation. The findings suggested that abnormal tRNA modification is a major contributor to disease pathogenesis.
Sources: Literature
Fetal anomalies v0.4297 YIPF5 Chirag Patel gene: YIPF5 was added
gene: YIPF5 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: YIPF5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIPF5 were set to PMID: 33164986
Phenotypes for gene: YIPF5 were set to Microcephaly, epilepsy, and diabetes syndrome 2 , MIM#619278
Review for gene: YIPF5 was set to GREEN
Added comment: 6 patients from 5 consanguineous families who had microcephaly, epilepsy, and diabetes syndrome (MEDS). All had severe microcephaly (standard deviation of -6.2); epilepsy diagnosed at ages ranging from 1 to 7 months; and neonatal/early-onset diabetes. All patients had low birth weight consistent with reduced insulin secretion in utero.
Sources: Expert list
Fetal anomalies v0.4273 HERC1 Krithika Murali gene: HERC1 was added
gene: HERC1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: HERC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: HERC1 were set to 28323226; 27108999; 26153217; 26138117
Phenotypes for gene: HERC1 were set to Macrocephaly, dysmorphic facies, and psychomotor retardation - MIM#617011
Review for gene: HERC1 was set to GREEN
Added comment: Multiple individuals reported with macrosomia and macrocephaly detected at birth.
Sources: Literature
Fetal anomalies v0.4273 FIBP Krithika Murali gene: FIBP was added
gene: FIBP was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FIBP was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FIBP were set to 27183861; 26660953
Phenotypes for gene: FIBP were set to Thauvin-Robinet-Faivre syndrome - MIM#617107
Review for gene: FIBP was set to AMBER
Added comment: Thauvin-Robinet-Faivre syndrome is an autosomal recessive disorder characterized by generalized overgrowth, mainly of height, and mildly delayed psychomotor development with mild or severe learning difficulties. More variable features may include congenital heart defects, kidney abnormalities, and skeletal defects. Patients may have an increased risk for Wilms tumor.

2 unrelated families reported.

27183861 - report one family with 3 affected children. Prenatally relevant phenotypic features include:
- congenital heart disease in one child
- preterm delivery and bilateral talipes equinovarus 2nd child
- cystic kidney disease, nephromegaly and polyhydramnios 3rd child

26660953 - report one child with ventricular septal defect, mitral valve prolapse, renal malrotation with left bifid ureter, macrocephaly and macrosomia noted at birth.
Sources: Literature
Fetal anomalies v0.4255 PPP2R3C Chirag Patel gene: PPP2R3C was added
gene: PPP2R3C was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PPP2R3C was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PPP2R3C were set to PMID: 30893644, 34714774, 34750818
Phenotypes for gene: PPP2R3C were set to Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy, OMIM # 618419
Review for gene: PPP2R3C was set to GREEN
Added comment: Gonadal dysgenesis, dysmorphic facies, retinal dystrophy, and myopathy (GDRM) is characterized by 46,XY complete gonadal dysgenesis in association with extragonadal anomalies, low birth weight, typical facial gestalt, rod and cone dystrophy, sensorineural hearing loss, omphalocele, anal atresia, renal agenesis, skeletal abnormalities, dry and scaly skin, severe myopathy, and neuromotor delay. 11 unrelated families with syndromic complete gonadal dysgenesis. 9 families had 46,XY females with complete gonadal dysgenesis, but 2 families had 46,XX patients with hypergonadotropic hypogonadism, nonvisualized gonads, primary amenorrhea, and absence of secondary sexual characteristics. Variants segregated with disease in each family and were not found in ethnically matched controls or in public variant databases. The heterozygous fathers exhibited morphologic abnormalities of spermatozoa and reduced fertility.
Sources: Literature
Fetal anomalies v0.4251 NHEJ1 Alison Yeung Phenotypes for gene: NHEJ1 were changed from Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 611291 to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291; Cernunnos-XLF deficiency MONDO:0012650
Fetal anomalies v0.4249 NHEJ1 Alison Yeung reviewed gene: NHEJ1: Rating: GREEN; Mode of pathogenicity: None; Publications: 30898087, 30666249, 28741180, 25288157, 24511403, 21721379, 21535335; Phenotypes: Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation, MIM# 611291, Cernunnos-XLF deficiency MONDO:0012650; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.4180 MIA3 Chirag Patel gene: MIA3 was added
gene: MIA3 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: MIA3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MIA3 were set to PMID: 32101163, 33778321
Phenotypes for gene: MIA3 were set to Ondontochondrodysplasia 2 with hearing loss and diabetes , MIM#619269
Review for gene: MIA3 was set to AMBER
Added comment: Odontochondrodysplasia-2 with hearing loss and diabetes (ODCD2) is characterized by growth retardation with proportionate short stature, dentinogenesis imperfecta, sensorineural hearing loss, insulin-dependent diabetes, and mild intellectual disability. Four affected siblings reported, homozygous variant affecting splicing. Mouse model has absence of bone mineralization. Can present with IUGR antenatally. Suitable for fetal anomalies panel.
Sources: Expert list
Fetal anomalies v0.4161 RAD50 Chirag Patel gene: RAD50 was added
gene: RAD50 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: RAD50 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RAD50 were set to PMID: 19409520; 32212377; 33378670
Phenotypes for gene: RAD50 were set to Nijmegen breakage syndrome-like disorder, MIM# 613078; MONDO:0013118
Review for gene: RAD50 was set to GREEN
Added comment: Nijmegen breakage syndrome-like disorder (NBSLD) is an autosomal recessive disorder characterized by severe prenatal growth retardation and persistent postnatal growth restriction, congenital microcephaly, borderline to mildly impaired intellectual development, normal sexual development, and radioresistant DNA synthesis with no immunodeficiency, myelodysplasia, or early neurodegeneration. Three unrelated families reported.
Sources: Expert list
Fetal anomalies v0.4157 FRA10AC1 Chirag Patel gene: FRA10AC1 was added
gene: FRA10AC1 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: FRA10AC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FRA10AC1 were set to PMID: 34694367
Phenotypes for gene: FRA10AC1 were set to Neurodevelopmental disorder, MONDO:0700092, FRA10AC1-related
Review for gene: FRA10AC1 was set to GREEN
Added comment: 5 individuals from 3 unrelated families reported. Variable ID, possibly related to variant type with LoF variants associated with more severe ID. All individuals had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism.
Sources: Expert list
Fetal anomalies v0.4155 DNA2 Chirag Patel gene: DNA2 was added
gene: DNA2 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: DNA2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: DNA2 were set to PMID: 24389050; 31045292
Phenotypes for gene: DNA2 were set to Seckel syndrome 8, MIM#615807
Review for gene: DNA2 was set to GREEN
Added comment: Three families described with bi-allelic variants in this gene and a primordial dwarfism/Seckel syndrome phenotype (intrauterine growth retardation, dwarfism, microcephaly with mental retardation, and a characteristic 'bird-headed' facial appearance). Note this gene is associated with multiple phenotypes.
Sources: Expert list
Fetal anomalies v0.4153 BRD4 Chirag Patel gene: BRD4 was added
gene: BRD4 was added to Fetal anomalies. Sources: Expert list
Mode of inheritance for gene: BRD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: BRD4 were set to PMID: 29379197, 30302754, 11997514, 34035299
Phenotypes for gene: BRD4 were set to Cornelia de Lange syndrome (no OMIM# yet)
Review for gene: BRD4 was set to GREEN
Added comment: Cornelia de Lange syndrome is a clinically heterogeneous developmental disorder characterized by malformations affecting multiple systems. Affected individuals have dysmorphic facial features, cleft palate, distal limb defects, prenatal onset growth retardation, and developmental delay. About 1% of patients have mutations in the BRD4 gene. % patients reported with functional evidence.
Sources: Expert list
Fetal anomalies v0.4132 ALG14 Belinda Chong gene: ALG14 was added
gene: ALG14 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ALG14 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ALG14 were set to 23404334; 28733338; 30221345; 23404334; 28733338
Phenotypes for gene: ALG14 were set to Myasthenic syndrome, congenital, 15, without tubular aggregates 616227; Intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies (IDDEBF), MIM#619031; Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036; Disorder of N-glycosylation
Review for gene: ALG14 was set to GREEN
gene: ALG14 was marked as current diagnostic
Added comment: Three OMIM disorders however, only Myopathy, epilepsy, and progressive cerebral atrophy, MIM# 619036 with prenatal manifestations.

5 individuals from unrelated families described in the literature: one with myasthenic syndrome, no report of ID; second with predominantly ID phenotype; and three more with a neurodegenerative phenotype. ALG14 is part of the UDP-GlcNAc transferase, which catalyzes a key step in endoplasmic reticulum N-linked glycosylation. The three OMIM disorders may represent a spectrum of severity for CDG.
Sources: Literature
Fetal anomalies v0.4132 SPATA5 Zornitza Stark Phenotypes for gene: SPATA5 were changed from EPILEPSY, HEARING LOSS, AND MENTAL RETARDATION SYNDROME to Epilepsy, hearing loss, and mental retardation syndrome MIM#616577
Fetal anomalies v0.4106 TAF1 Zornitza Stark Phenotypes for gene: TAF1 were changed from Dysmorphic Features, Intellectual Disability, and Neurological Manifestations to Mental retardation, X-linked, syndromic 33, MIM# 300966
Fetal anomalies v0.4066 TINF2 Zornitza Stark Phenotypes for gene: TINF2 were changed from EXUDATIVE RETINOPATHY WITH BONE MARROW FAILURE to Revesz syndrome, MIM# 268130
Fetal anomalies v0.4041 TRAPPC9 Zornitza Stark Phenotypes for gene: TRAPPC9 were changed from MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 13 to Intellectual disability, autosomal recessive 13 (MIM# 613192)
Fetal anomalies v0.4036 TRIP12 Zornitza Stark Phenotypes for gene: TRIP12 were changed from TRIP12-related intellectual disability with/without autism spectrum disorder to Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752
Fetal anomalies v0.4032 TRIP12 Zornitza Stark reviewed gene: TRIP12: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation autosomal dominant 49, Clark-Baraitser Syndrome, MIM#617752; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.4027 TTC8 Zornitza Stark Phenotypes for gene: TTC8 were changed from RETINITIS PIGMENTOSA TYPE 51; BARDET-BIEDL SYNDROME TYPE 8 to Bardet-Biedl syndrome 8, MIM# 615985
Fetal anomalies v0.4016 TUBGCP6 Zornitza Stark Phenotypes for gene: TUBGCP6 were changed from MICROCEPHALY AND CHORIORETINOPATHY WITH OR WITHOUT MENTAL RETARDATION to Microcephaly and chorioretinopathy, autosomal recessive, 1, MIM#251270
Fetal anomalies v0.4012 UBE3B Zornitza Stark Phenotypes for gene: UBE3B were changed from BLEPHAROPHIMOSIS-MENTAL RETARDATION to Kaufman oculocerebrofacial syndrome, MIM# 244450; MONDO:0009485
Fetal anomalies v0.3988 ZNF711 Zornitza Stark Phenotypes for gene: ZNF711 were changed from MENTAL RETARDATION X-LINKED ZNF711-RELATED to Mental retardation, X-linked 97, OMIM #300803
Fetal anomalies v0.3986 ZNF711 Zornitza Stark reviewed gene: ZNF711: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked 97, OMIM #300803; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3972 UPF3B Zornitza Stark Phenotypes for gene: UPF3B were changed from MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 14 to Mental retardation, X-linked, syndromic 14, MIM# 300676
Fetal anomalies v0.3964 UBE2A Zornitza Stark Phenotypes for gene: UBE2A were changed from UBE2A-RELATED X-LINKED SYNDROMIC MENTAL RETARDATION to Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860)
Fetal anomalies v0.3962 UBE2A Zornitza Stark reviewed gene: UBE2A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked syndromic, Nascimento-type (MIM#300860); Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3960 TUSC3 Zornitza Stark Phenotypes for gene: TUSC3 were changed from MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 7 to Mental retardation, autosomal recessive 7, MIM# 611093, MONDO:0012615; TUSC3-CDG (Disorders of protein N-glycosylation)
Fetal anomalies v0.3946 SYNGAP1 Zornitza Stark Phenotypes for gene: SYNGAP1 were changed from MENTAL RETARDATION AUTOSOMAL DOMINANT TYPE 5; EPILEPTIC ENCEPHALOPATHY to Intellectual disability, autosomal dominant 5 (MIM # 612621)
Fetal anomalies v0.3943 STAG1 Zornitza Stark Phenotypes for gene: STAG1 were changed from STAG1 syndromic intellectual disability to Mental retardation, autosomal dominant 47, MIM# 617635
Fetal anomalies v0.3940 SLC9A6 Zornitza Stark Phenotypes for gene: SLC9A6 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED CHRISTIANSON TYPE to Mental retardation, X-linked syndromic, Christianson type, MIM# 300243; MONDO:0010278
Fetal anomalies v0.3934 SLC37A4 Zornitza Stark changed review comment from: Bi-allelic LOF variants in this gene cause glycogen storage disorder.

Single individual reported with heterozygous de novo variant in this gene. Clinical features included dysmorphic features (low set ears, a broad nose, mandibular micrognathia and facial asymmetry) and hepatopathy. The variant abolishes the ER retention signal of the transporter and generates a weak Golgi retention signal. Intracellular mislocalization of the transporter is postulated to lead to a congenital disorder of glycosylation instead of glycogen storage disease.
Sources: Literature; to: Bi-allelic LOF variants in this gene cause glycogen storage disorder. Clinical presentation is typically post-natal.

Single individual reported with heterozygous de novo variant in this gene. Clinical features included dysmorphic features (low set ears, a broad nose, mandibular micrognathia and facial asymmetry) and hepatopathy. The variant abolishes the ER retention signal of the transporter and generates a weak Golgi retention signal. Intracellular mislocalization of the transporter is postulated to lead to a congenital disorder of glycosylation instead of glycogen storage disease.
Sources: Literature
Fetal anomalies v0.3920 PURA Zornitza Stark Phenotypes for gene: PURA were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 31, MIM# 616158
Fetal anomalies v0.3908 PLOD3 Krithika Murali gene: PLOD3 was added
gene: PLOD3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PLOD3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PLOD3 were set to 30237576; 18834968
Phenotypes for gene: PLOD3 were set to Lysyl hydroxylase 3 deficiency - MIM#612394
Review for gene: PLOD3 was set to GREEN
Added comment: 4 unrelated families reported with biallelic PLOD3 variants and Stickler-syndrome like phenotype including antenatal phenotype of IUGR in one family.
--
PMID 30237576 Maddirevula et al 2019 - report homozygous nonsense variant in a proband with dysmorphic facies, microcephaly, ptosis and contractures. No antenatal information provided.

PMID 31129566 Ewans et al 2019 - report 3 affected siblings with a Stickler-syndrome like disorder.
- Patient 1 had congenital nystagmus and presented with hearing loss and myopia. On examination aged 2, noted to have dysmorphic features - prominent eyes, hypertelorism, malar hypoplasia, an upturned nose, low-set ears and microretrognathia.
- Patient 2 noted to have camptodactyly and clinodactyly postnatally. On examination age 5 noted to have DIP joint contractures and mild skin syndactyly.
- Patient 3 - breech delivery. bilateral hand foot camptodactyly, facial dysmorphism.
- No antenatal features reported.

PMID 30463024 Vahidnehzad et al 2019 - report a male proband from a consanguineous Iranian Baloch family referred for assessment age 4.5. Noted to have developmental delay, musculoskeletal manifestations including scoliosis, flexion contractions, cutaneous syndactyly, right diaphragmatic eventration, ocular anomalies, growth failure and skin blisters. No concerns antenatally. Postnatally noted to have cataract and facial dysmorphism (midface hypoplasia). Homozygous PLOD3 missense variant identified, parents unaffected carriers. PLOD3 mRNA levels in the patient’s fibroblasts measured by whole-transcriptome sequencing and confirmed by RT-PCR, were the same as in control cells, however, the expression of type VII collagen was reduced significantly. No antenatal features reported.

PMID: 18834968 Salo et al 2008 - a female proband with significant IUGR, characteristic craniofacial profile, diaphragm eventration, skeletal anomalies (bilateral talipes equinovarus, flexion contractures, scoliosis from age 7), skin anomalies incl blistering and ocular anomalies. One 28 week male stillborn sibling noted to have significant IUGR and skeletal anomalies on post-mortem. Supportive functional evidence. Compound het PLOD3 variants.
Sources: Literature
Fetal anomalies v0.3873 SOX17 Zornitza Stark Phenotypes for gene: SOX17 were changed from VESICOURETERAL REFLUX TYPE 3 to Vesicoureteral reflux 3 MIM#613674; Pulmonary arterial hypertension
Fetal anomalies v0.3869 PRRT2 Zornitza Stark Phenotypes for gene: PRRT2 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; BENIGN FAMILIAL INFANTILE EPILEPSY AND INFANTILE CONVULSIONS WITH CHOREOATHETOSIS SYNDROME to Convulsions, familial infantile, with paroxysmal choreoathetosis, MIM# 602066; Episodic kinesigenic dyskinesia 1, MIM# 128200; Seizures, benign familial infantile, 2, MIM# 605751; intellectual disability, autosomal recessive
Fetal anomalies v0.3853 PDHB Zornitza Stark edited their review of gene: PDHB: Added comment: Fetal presentation at 22 weeks reported with intrauterine growth retardation, short corpus callosum, ventricular dilation, and cerebellar hypoplasia, PMID 26865159.; Changed publications: 15138885, 26014431, 26865159
Fetal anomalies v0.3843 SOX17 Daniel Flanagan reviewed gene: SOX17: Rating: RED; Mode of pathogenicity: None; Publications: 29650961, 31406341; Phenotypes: Vesicoureteral reflux 3 MIM#613674, Pulmonary arterial hypertension; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3837 MYT1L Zornitza Stark Phenotypes for gene: MYT1L were changed from MYT1L syndrome to Mental retardation, autosomal dominant 39, MIM# 616521
Fetal anomalies v0.3819 MECP2 Zornitza Stark Phenotypes for gene: MECP2 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 13; MENTAL RETARDATION SYNDROMIC X-LINKED LUBS TYPE; CHROMOSOME XQ28 DUPLICATION SYNDROME; ENCEPHALOPATHY NEONATAL SEVERE DUE TO MECP2 MUTATIONS; RETT SYNDROME (RTT)[ to Rett syndrome, MIM# 312750; Encephalopathy, neonatal severe 300673
Fetal anomalies v0.3818 MECP2 Zornitza Stark changed review comment from: Well established gene-disease association, microcephaly is a key phenotypic feature both in Rett syndrome and in males affected by severe neonatal encephalopathy.; to: Well established gene-disease association, typically presents post-natally.
Fetal anomalies v0.3779 PLK4 Zornitza Stark Phenotypes for gene: PLK4 were changed from MICROCEPHALY, GROWTH FAILURE AND RETINOPATHY to Microcephaly and chorioretinopathy, autosomal recessive, 2, OMIM #616171
Fetal anomalies v0.3768 TBCE Zornitza Stark Phenotypes for gene: TBCE were changed from HYPOPARATHYROIDISM-RETARDATION-DYSMORPHISM SYNDROME; Early-Onset Progressive Encephalopathy with Distal Spinal Muscular Atrophy; KENNY-CAFFEY SYNDROME TYPE 1 to Hypoparathyroidism-retardation-dysmorphism syndrome, OMIM #241410; Kenny-Caffey syndrome, type 1, OMIM #244460; Encephalopathy, progressive, with amyotrophy and optic atrophy OMIM #617207
Fetal anomalies v0.3722 PLK4 Chirag Patel reviewed gene: PLK4: Rating: GREEN; Mode of pathogenicity: None; Publications: PubMed: 25344692, 25320347, 33756487, 27650967; Phenotypes: Microcephaly and chorioretinopathy, autosomal recessive, 2, OMIM #616171; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3721 TBCE Chirag Patel reviewed gene: TBCE: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 12389028, 27666369; Phenotypes: Hypoparathyroidism-retardation-dysmorphism syndrome, OMIM #241410, Kenny-Caffey syndrome, type 1, OMIM #244460, Encephalopathy, progressive, with amyotrophy and optic atrophy OMIM #617207; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3708 IQSEC2 Zornitza Stark Phenotypes for gene: IQSEC2 were changed from MENTAL RETARDATION X-LINKED TYPE 1 to Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347
Fetal anomalies v0.3697 HECW2 Zornitza Stark changed review comment from: Typically denovo missense variants in the HECT domain.
PMID: 29807643 - R1191Q single case with severe D/ID, EE and regression
PMID: 29395664 - single case with regression, loss of swallowing, increased abnormal movements/hand stereotypies, Rett like, cortical visual impairment and EE
PMID: 27334371 - propose GOF or dominant negative; 1 case plus references 5 previous cases
PMID: 27389779 - four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. p. Arg1330Trp, p.Glu1445Gly reported >1 case.
Regression reported in the context of refractory EE; to: Clinical presentation is typically post-natal.

Typically denovo missense variants in the HECT domain.
PMID: 29807643 - R1191Q single case with severe D/ID, EE and regression
PMID: 29395664 - single case with regression, loss of swallowing, increased abnormal movements/hand stereotypies, Rett like, cortical visual impairment and EE
PMID: 27334371 - propose GOF or dominant negative; 1 case plus references 5 previous cases
PMID: 27389779 - four novel de novo predicted deleterious missense variants in HECW2 in six probands with ID/developmental delay and hypotonia. Other common features include seizures, strabismus, nystagmus, cortical visual impairment and dysmorphic facial features. p. Arg1330Trp, p.Glu1445Gly reported >1 case.
Regression reported in the context of refractory EE
Fetal anomalies v0.3697 HDAC4 Zornitza Stark Phenotypes for gene: HDAC4 were changed from BRACHYDACTYLY-MENTAL RETARDATION SYNDROME to Brachydactyly mental retardation syndrome; Brachydactyly without intellectual disability
Fetal anomalies v0.3692 HACE1 Zornitza Stark Phenotypes for gene: HACE1 were changed from HACE1 related disorder to Spastic paraplegia and psychomotor retardation with or without seizures, 616756; MONDO:0014764
Fetal anomalies v0.3685 GRIN2A Zornitza Stark Phenotypes for gene: GRIN2A were changed from EPILEPSY WITH NEURODEVELOPMENTAL DEFECTS; LANDAU-KLEFFNER SYNDROME to Epilepsy, focal, with speech disorder and with or without mental retardation, MIM# 245570
Fetal anomalies v0.3681 GRIK2 Zornitza Stark Phenotypes for gene: GRIK2 were changed from MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 6 to Neurodevelopmental disorder with impaired language and ataxia and with or without seizures, MIM# 619580
Fetal anomalies v0.3677 GRIA3 Zornitza Stark Phenotypes for gene: GRIA3 were changed from MENTAL RETARDATION X-LINKED TYPE 94 to Intellectual developmental disorder, X-linked, syndromic, Wu type (MIM#300699)
Fetal anomalies v0.3674 GMPPA Zornitza Stark Phenotypes for gene: GMPPA were changed from GLYCOSYLATION DISORDER CHARACTERIZED BY INTELLECTUAL DISABILITY AND AUTONOMIC DYSFUNCTION to Alacrima, achalasia, and mental retardation syndrome (MIM# 615510)
Fetal anomalies v0.3672 GMPPA Zornitza Stark reviewed gene: GMPPA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Alacrima, achalasia, and mental retardation syndrome (MIM# 615510); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3648 FTSJ1 Zornitza Stark Phenotypes for gene: FTSJ1 were changed from MENTAL RETARDATION X-LINKED TYPE 44 to Intellectual developmental disorder, X-linked 9, MIM# 309549
Fetal anomalies v0.3646 FOXP1 Zornitza Stark Phenotypes for gene: FOXP1 were changed from MENTAL RETARDATION WITH LANGUAGE IMPAIRMENT AND AUTISTIC FEATURES to Mental retardation with language impairment and with or without autistic features, MIM# 613670
Fetal anomalies v0.3643 FLVCR1 Zornitza Stark Phenotypes for gene: FLVCR1 were changed from ATAXIA, POSTERIOR COLUMN, WITH RETINITIS PIGMENTOSA to Ataxia, posterior column, with retinitis pigmentosa, MIM#609033
Fetal anomalies v0.3621 DLG3 Zornitza Stark Phenotypes for gene: DLG3 were changed from MENTAL RETARDATION X-LINKED TYPE 90 to Mental retardation, X-linked 90, MIM#300850
Fetal anomalies v0.3617 DEAF1 Zornitza Stark Phenotypes for gene: DEAF1 were changed from Autism, intellectual disability, basal ganglia dysfunction and epilepsy; MENTAL RETARDATION, AUTOSOMAL DOMINANT 24 to Neurodevelopmental disorder with hypotonia, impaired expressive language, and with or without seizures 617171; Vulto-van Silfout-de Vries syndrome 615828
Fetal anomalies v0.3541 TBCK Zornitza Stark Phenotypes for gene: TBCK were changed from Severe Infantile Syndromic Encephalopathy to Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, MIM# 616900
Fetal anomalies v0.3539 TBCK Zornitza Stark reviewed gene: TBCK: Rating: GREEN; Mode of pathogenicity: None; Publications: 27040692, 30103036, 27040691; Phenotypes: Hypotonia, infantile, with psychomotor retardation and characteristic facies 3, MIM# 616900; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3539 TBL1XR1 Zornitza Stark Phenotypes for gene: TBL1XR1 were changed from Intellectual disability with autism spectrum disorder; Pierpont syndrome to Mental retardation, autosomal dominant 41, MIM# 616944; Pierpont syndrome, MIM# 602342
Fetal anomalies v0.3537 TBL1XR1 Zornitza Stark reviewed gene: TBL1XR1: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal dominant 41, MIM# 616944, Pierpont syndrome, MIM# 602342; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3510 TBC1D1 Krithika Murali gene: TBC1D1 was added
gene: TBC1D1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: TBC1D1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TBC1D1 were set to 26572137
Phenotypes for gene: TBC1D1 were set to CAKUT
Review for gene: TBC1D1 was set to GREEN
Added comment: No new publications since last PanelApp review included below

---
1 heterozygous de novo frameshift variant in TBC1D1 in 1 CAKUT.
3 further CAKUT cases with three novel or rare inherited heterozygous TBC1D1 missense variants predicted to be pathogenic. TBC1D1 mutations affected Ser237-phosphorylation or protein stability and thereby act as hypomorphs. Tbc1d1 showed widespread expression in the developing murine urogenital system. A mild CAKUT spectrum phenotype, including anomalies observed in patients carrying TBC1D1 mutations, was found in kidneys of some Tbc1d1 (-/-) mice. Significantly reduced Glut4 levels were detected in kidneys of Tbc1d1 (-/-) mice and the dysplastic kidney of a TBC1D1 mutation carrier versus controls. TBC1D1 and SLC2A4 encoding GLUT4 were highly expressed in human fetal kidney. These data demonstrate heterozygous deactivating TBC1D1 mutations in CAKUT patients with a similar renal and ureteral phenotype, and provide evidence that TBC1D1 mutations may contribute to CAKUT pathogenesis, possibly via a role in glucose homeostasis.
Sources: Literature
Fetal anomalies v0.3507 TMCO1 Zornitza Stark Phenotypes for gene: TMCO1 were changed from CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION SYNDROME to Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980
Fetal anomalies v0.3505 TMCO1 Zornitza Stark reviewed gene: TMCO1: Rating: GREEN; Mode of pathogenicity: None; Publications: 20018682, 23320496, 24194475, 30556256, 31102500; Phenotypes: Craniofacial dysmorphism, skeletal anomalies, and mental retardation syndrome, MIM# 213980; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3502 SLIT2 Krithika Murali gene: SLIT2 was added
gene: SLIT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SLIT2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: SLIT2 were set to 26026792; 15130495
Phenotypes for gene: SLIT2 were set to CAKUT; vesicoureteric reflux
Review for gene: SLIT2 was set to AMBER
Added comment: PMID 26026792 Hwang et al 2019 - identified three unrelated individuals with CAKUT and different heterozygous SLIT2 missense mutations.
- 1 patient presented with multiple bilateral subcortical renal cysts
- 1 patient presented with multicystic dysplastic kidneys
- 1 patient had right renal agenesis

Authors provide supportive variant-specific mouse models.

PMID: 34059960 Liu et al 2021 - 3 unrelated children from a Chinese Kidney Disease Database with vesicoureteric reflux had SLIT3 VUS identified

PMID 19350278 Zu et al 2009 - x2 unrelated individuals with SLIT2 variants - not segregating with disease in either family
Sources: Literature
Fetal anomalies v0.3464 ROBO2 Krithika Murali gene: ROBO2 was added
gene: ROBO2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ROBO2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ROBO2 were set to 18235093; 19350278; 24429398; 17357069; 26026792; 29194579; 34059960
Phenotypes for gene: ROBO2 were set to Vesicoureteral reflux 2 - MIM#610878; CAKUT
Review for gene: ROBO2 was set to GREEN
Added comment: Known association with familial vesicoureteral reflux and congenital anomalies of the kidney and urinary tract.
Sources: Literature
Fetal anomalies v0.3449 TNXB Zornitza Stark reviewed gene: TNXB: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Vesicoureteral reflux 8, MIM#615963; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3428 SYP Zornitza Stark Phenotypes for gene: SYP were changed from MENTAL RETARDATION X-LINKED SYP-RELATED to Intellectual developmental disorder, X-linked 96 (MIM#300802)
Fetal anomalies v0.3422 ZDHHC9 Zornitza Stark Phenotypes for gene: ZDHHC9 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED ZDHHC9-RELATED to Mental retardation, X-linked syndromic, Raymond type, MIM# 300799
Fetal anomalies v0.3420 ZDHHC9 Zornitza Stark reviewed gene: ZDHHC9: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, X-linked syndromic, Raymond type, MIM# 300799; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.3415 WDR45 Zornitza Stark Phenotypes for gene: WDR45 were changed from NEURODEGENERATION WITH BRAIN IRON ACCUMULATION to Neurodegeneration with brain iron accumulation 5, MIM# 300894; Rett syndrome; Rett-like phenotypes
Fetal anomalies v0.3413 COQ7 Krithika Murali gene: COQ7 was added
gene: COQ7 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COQ7 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: COQ7 were set to 33215859; 28125198; 31240163; 28409910; 26084283
Phenotypes for gene: COQ7 were set to Coenzyme Q10 deficiency, primary, 8 - MIM#616733
Review for gene: COQ7 was set to GREEN
Added comment: Biallelic variants associated with primary coenzyme Q10 (CoQ10) deficiency, a heterogeneous multi-system disorder including early-postnatal features such as neonatal encephalopathy, contractures. Antenatal features reported include IUGR, oligohydramnios, feetal lung hypoplasia, dysplastic kidneys.

Specifically for COQ7-related CoQ10 deficiency:

PMID 33215859 Hashemi et al 2020 - report two affected individuals from a consanguineous Iranian family with homozygous COQ7 variants progressive spastic paraparesis diagnosed at age 1.5-2 with normal antenatal history.

PMID 31240163 Kwong et al 2019 - report a patient with compound hetereozygous COQ7 variants, encephalo‐myo‐nephro‐cardiopathy, persistent lactic acidosis, and basal ganglia lesions resulting in early infantile death. Skin fibroblast studies showed decreased combined complex II + III activity and reduction in CoQ10 level. The proband was a DCDA twin, noted to have IUGR, oligohydramnios, cardiomegaly and tricuspid regurgitation antenatally.

PMID 28409910 Wang et al 2017 - no antenatal features reported in their proband

PMID 26084283 Freyer et al 2015 - report x1 patient with homozygous COQ7 variant. The pregnancy was complicated by oligohydramniosis, fetal lung hypoplasia and growth retardation.
Sources: Literature
Fetal anomalies v0.3400 LTBP1 Krithika Murali gene: LTBP1 was added
gene: LTBP1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LTBP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LTBP1 were set to 33991472
Phenotypes for gene: LTBP1 were set to Cutis laxa, autosomal recessive, type IIE - MIM#619451
Review for gene: LTBP1 was set to GREEN
Added comment: Homozygous premature truncating LTBP1 variants in eight affected individuals from four unrelated consanguineous families reported associated with autosomal recessive cutis laxa type IIE. Phenotypic features relevant in the prenatal setting include:
- Congenital diaphragmatic hernia (1 individual)
- Cleft palate (2 individuals)
- Congenital heart defects
- Renal anomalies (1 individual)
- Microretrognathia (1 individual)
- Hydrocephalus (1 individual)
- Skeletal anomalies (craniosynostosis, short stature, brachydactyly, and syndactyly).

Supportive patient-derived fibroblast and zebrafish studies.
Sources: Literature
Fetal anomalies v0.3400 TNXB Daniel Flanagan reviewed gene: TNXB: Rating: RED; Mode of pathogenicity: None; Publications: 19921645, 28306229, 28306225, 23620400; Phenotypes: Vesicoureteral reflux 8 (MIM#615963), Ehlers-Danlos syndrome, classic-like, 1 (MIM#606408); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.3396 ZDHHC9 Ain Roesley reviewed gene: ZDHHC9: Rating: RED; Mode of pathogenicity: None; Publications: Mental retardation, X-linked syndromic, Raymond typeMIM# 300799; Phenotypes: Mental retardation, X-linked syndromic, Raymond typeMIM# 300799; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females; Current diagnostic: yes
Fetal anomalies v0.3377 WDR45 Ain Roesley reviewed gene: WDR45: Rating: RED; Mode of pathogenicity: None; Publications: 30842224, 23176820; Phenotypes: Neurodegeneration with brain iron accumulation 5, MIM# 300894, Rett syndrome, Rett-like phenotypes; Mode of inheritance: None; Current diagnostic: yes
Fetal anomalies v0.3372 SMARCAL1 Daniel Flanagan changed review comment from: Well-established gene-disease association; over 40 patients with biallelic mutations in SMARCAL1; Zebrafish and mouse models that recapitulates phenotype have been reported.

This disorder combines abnormality of the immune and skeletal systems. Primary features include growth retardation (IUGR in 50%), renal failure, cerebral infarcts, skin pigmentation and CID (lymphocytopaenia, recurrent infections and/or T-cell immunodeficiency) beginning in childhood.

GeneReviews: Short stature (99% of individuals) that typically manifests as a short neck and trunk with lumbar lordosis and a protruding abdomen.; to: Well-established gene-disease association; over 40 patients with biallelic mutations in SMARCAL1; Zebrafish and mouse models that recapitulates phenotype have been reported.

This disorder combines abnormality of the immune and skeletal systems. Primary features include growth retardation (IUGR in 50%), renal failure, cerebral infarcts, skin pigmentation and CID (lymphocytopaenia, recurrent infections and/or T-cell immunodeficiency) beginning in childhood.

GeneReviews: Short stature (99% of individuals) that typically manifests as a short neck and trunk with lumbar lordosis and a protruding abdomen. Most affected children have prenatal and postnatal disproportionate growth failure. A few have normal intrauterine growth followed by postnatal growth failure.
Fetal anomalies v0.3372 MAN1B1 Zornitza Stark Phenotypes for gene: MAN1B1 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Rafiq syndrome, MIM# 614202
Fetal anomalies v0.3351 KPTN Zornitza Stark Phenotypes for gene: KPTN were changed from MACROCEPHALY, NEURODEVELOPMENTAL DELAY, AND SEIZURES to Mental retardation, autosomal recessive 41 (MIM#615637)
Fetal anomalies v0.3333 NEXMIF Zornitza Stark Phenotypes for gene: NEXMIF were changed from Intellectual disability and epilepsy; KIAA2022 to Mental retardation, X-linked 98 300912
Fetal anomalies v0.3327 NONO Zornitza Stark Phenotypes for gene: NONO were changed from Atresia; Ventricular septal defect (VSD); Pulmonary stenosis; Ebstein s anomaly; Left ventricular non-compaction cardiomyopathy (LVNC) to Mental retardation, X-linked, syndromic 34, MIM# 300967; Ventricular septal defect (VSD); Pulmonary stenosis; Ebstein s anomaly; Left ventricular non-compaction cardiomyopathy (LVNC)
Fetal anomalies v0.3321 KDM1A Zornitza Stark Phenotypes for gene: KDM1A were changed from Developmental delay and distinctive facial features to Cleft palate, psychomotor retardation, and distinctive facial features 616728
Fetal anomalies v0.3317 KCNQ5 Zornitza Stark Phenotypes for gene: KCNQ5 were changed from Intellectual Disability with or without Epileptic Encephalopathy to Mental retardation, autosomal dominant 46, MIM# 617601
Fetal anomalies v0.3295 IRX5 Zornitza Stark Phenotypes for gene: IRX5 were changed from HYPERTELORISM, SEVERE, WITH MIDFACE PROMINENCE, MYOPIA, MENTAL RETARDATION, AND BONE FRAGILITY to Hamamy syndrome, MIM# 611174
Fetal anomalies v0.3279 ZBTB24 Krithika Murali gene: ZBTB24 was added
gene: ZBTB24 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ZBTB24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ZBTB24 were set to 32865561; 21596365; 29023266; 32061411; 21906047; 28128455; 23739126; 22786748
Phenotypes for gene: ZBTB24 were set to Immunodeficiency-centromeric instability-facial anomalies syndrome 2 - MIM#614069
Review for gene: ZBTB24 was set to GREEN
Added comment: Well reported association with ICF2 (immunodeficiency-centromeric instability facial anomalies syndrome 2). Patients have immunodeficiency (mainly hypo/agammaglobulinemia in the presence of B cells), recurrent infections (namely respiratory and gastrointestinal) and dysmorphic facies.

Although antenatal features not thoroughly described for published cases, low birth weight has been a reported feature as well as hypertelorism and micrognathia/retrognathia - these have the potential to be detected prenatally.

PMID 32865561 Helfricht et al 2020 - "loss of ZBTB24 in B cells from mice and ICF2 patients affects nonhomologous end-joining (NHEJ) during immunoglobulin class-switch recombination and consequently impairs immunoglobulin production and isotype balance".

PMID 32061411 Banday. et al 2020 - report a patient with this condition and granulomatous hepatitis. Review phenotype of previously reported patients, low birth weight and facial dysmorphism including micrognathia noted in other cases.

PMID 29023266 Conrad et al 2017 - describe a 17 month old boy with recurrent infections, growth failure, facial anomalies (including hyperterlorism/low set ears), and inflammatory bowel disease. No antenatal information.

PMID 28128455 van den Boogaard 2017 - 5 new patients described

PMID 23739126 Nitta et al 2013 - report 3 unrelated patients, x1 patient - lower birth weight and head circumference. At age 5 had macrocephaly, hyperterlorism. Noted to have bilateral hydronephrosis. x1 patient BW 2660g, micrognathia, hyperterlorism.

PMID 21906047 Chouery et al 2012 - 3 siblings from a Lebanese family with novel homozygous LoF variant. Apparently normal pregnancies, at time of diagnostic assessment HC between the 5th and 15th centiles, height below the 5th percentile. Dysmorphic features including high arched palate, small chin, retrognathism and everted lower lips.

PMID 22786748 Cerbone et al 2012 - report an 8 year old M of consanguineous Moroccan ancestry with ID, dysmorphic features, cafe au last macules and a large arachnoid cyst in the right temporal region, causing compression of the temporal lobe and lateral ventricle

PMID 21596365 de Greef et al 2011 - report 4 new unrelated patients, no antenatal information
Sources: Literature
Fetal anomalies v0.3235 UQCC2 Krithika Murali gene: UQCC2 was added
gene: UQCC2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: UQCC2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: UQCC2 were set to 24385928; 28804536
Phenotypes for gene: UQCC2 were set to Mitochondrial complex III deficiency, nuclear type 7 - MIM#615824
Review for gene: UQCC2 was set to GREEN
Added comment: Biallelic variants associated with mitochondrial complex III deficiency. 2 unrelated families and variant-specific functional evidence/segregation information provided.

PMID 24385928 Tucker et al 2013 - report a patient with homozygous splice site UQCC2 variants. Presented with severe intrauterine growth retardation, neonatal lactic acidosis and renal tubular dysfunction of consanguineous Lebanese ancestry. Supportive functional studies including using patient fibroblasts.

PMID: 28804536 Feichtinger et al 2017 - report a second unrelated patient of consanguineous Turkish ancestry with UQCC2 deficiency, a female infant born at 32 weeks gestation after a a pregnancy complicated by IUGR and oligohydramnios. Followed by a fulminant postnatal course including respiratory distress syndrome, developed epileptic seizures progressing to status epilepticus, profound lactic acidosis with elevated urinary pyruvate and death at day 33 of life. Homozygous missense UQCC2 variants identified leading to a severe reduction of UQCC2 protein in patient's muscle and fibroblast cells.
Sources: Literature
Fetal anomalies v0.3213 GABRA1 Zornitza Stark Phenotypes for gene: GABRA1 were changed from JUVENILE MYOCLONIC EPILEPSY; EPILEPTIC ENCEPHALOPATHY to Epileptic encephalopathy, early infantile, 19 615744; Rett syndrome; Rett-like phenotypes; idiopathic generalized Epilepsy; Dravet syndrome
Fetal anomalies v0.3209 GABRA1 Zornitza Stark changed review comment from: PMID: 11992121; 1 large family with Juvenile Myoclonic Epilepsy PMID: 21714819; 2 probands with idiopathic generalized epilepsy PMID: 24623842; 4 patients with Dravet syndrome PMID: 30842224; non-MECP2 probands with Rett-like syndromes categorised into 1) typical RTT, 2) atypical RTT, 3) RTT-like phenotype. Total of 1 family with SNV in GABRA1 in Rett-like cohort.; to: PMID: 11992121; 1 large family with Juvenile Myoclonic Epilepsy PMID: 21714819; 2 probands with idiopathic generalized epilepsy PMID: 24623842; 4 patients with Dravet syndrome PMID: 30842224; non-MECP2 probands with Rett-like syndromes categorised into 1) typical RTT, 2) atypical RTT, 3) RTT-like phenotype. Total of 1 family with SNV in GABRA1 in Rett-like cohort.

Typically presents post-natally.
Fetal anomalies v0.3197 FRMPD4 Zornitza Stark changed review comment from: Multiple affected individuals from unrelated families.; to: Multiple affected individuals from unrelated families. Corpus callosum abnormalities, retrognathia reported.
Fetal anomalies v0.3175 RAB39B Zornitza Stark Phenotypes for gene: RAB39B were changed from MENTAL RETARDATION X-LINKED TYPE 72 (MRX72) +/- PARKINSONS to Intellectual developmental disorder, X-linked 72 MIM#300271; Waisman syndrome MIM#311510
Fetal anomalies v0.3168 PRSS12 Zornitza Stark Phenotypes for gene: PRSS12 were changed from MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 1 to Intellectual disability, PRSS12 related MIM#249500
Fetal anomalies v0.3151 METTL23 Krithika Murali gene: METTL23 was added
gene: METTL23 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: METTL23 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: METTL23 were set to 32878022; 32439618; 32067349; 24626631; 24501276
Phenotypes for gene: METTL23 were set to Mental retardation, autosomal recessive 44 - #615942
Review for gene: METTL23 was set to RED
Added comment: Biallelic variants associated with syndromic ID. Published studies provide no or limited antenatal information with no consistent prenatal phenotype described.

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PMID: 32878022 – Khan et al 2020 - homozygous missense variants identified in consanguineous Pakistani family with 3 affected siblings having ID, epilepsy, behavioural issues, hypotonia and dysmorphic features (prominent large-size eyes, eyebrows, ears, short upturned nose with flat nasal bridge, and thin upper lip). Authors report that prenatal, perinatal and neonatal medical records of all patients were normal.

PMID 32439618 – Smaili et al 2020 report two Moroccan siblings presenting with mild intellectual disability and dysmorphic features. WES identified homozygous METTL23 gene variants. Describe uneventful pregnancies and postnatal course. Macrocephaly reported in both siblings (HC 52cm in a 7 year old M and 50cm in 6 yo F) - no information regarding HC of parents provided, macrocephaly not a consistently reported feature of this condition.

PMID: 32067349 – Almannai et al 2020 - 6 individuals from 4 families - 2 families unrelated, 2 families come from same Saudi tribe and are therefore likely to be distantly related with same homozygous METTL23 variant identified in both. No prenatal features or immediate postnatal issues described related to this condtion. One subject reported to have an MRI-B showing mild ventriculomegaly at a later age which may reflect mild white matter volume loss. This subject also had a 618 Kilobases duplication at 7p11.2 (57,261,112-57,878,853) identified on CGH array.

PMID: 24626631 – Bernkopf 2014 - describe 2 unrelated families. Provide no antenatal information or report no issues antenatally/at birth apart from one baby being large and cyanosed postnatally

PMID: 24501276 – Reiff et al 2014 - report 7 affected members of a large, consanguineous Arab family with ID and mild dysmorphic features. X1 patient had cleft uvula and submucosal cleft palate.
Sources: Literature
Fetal anomalies v0.3151 LRRC32 Krithika Murali gene: LRRC32 was added
gene: LRRC32 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LRRC32 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: LRRC32 were set to 30976112
Phenotypes for gene: LRRC32 were set to Cleft palate, proliferative retinopathy, and developmental delay - MIM#619074
Review for gene: LRRC32 was set to AMBER
Added comment: Gene previously reviewed for PanelApp Feb 2021 - no new relevant publications since

--

Three individuals from two consanguineous families with cleft palate, proliferative retinopathy, and developmental delay had the same homozygous biallelic variant, c.1630C>T; p.(Arg544Ter), segregated and shared haplotype indicative of founder effect. Mouse model has cleft palate and neonatal death.
Sources: Literature
Fetal anomalies v0.3151 LRP6 Krithika Murali gene: LRP6 was added
gene: LRP6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: LRP6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: LRP6 were set to 16126904; 30950205; 26387593; 26963285; 28813618; 29500247; 33164649; 34306029
Phenotypes for gene: LRP6 were set to Tooth agenesis, selective, 7 - MIM#616724; cleft lip/palate
Review for gene: LRP6 was set to AMBER
Added comment: LoF variants known to be associated with tooth agenesis. In addition, x2 unrelated families from 2 different studies with heterozygous LRP6 variant had tooth agenesis and cleft lip/palate (PMID 29500247; 26963285). Growth failure reported in some individuals but unclear if prenatal in onset (PMID 26963285). Minor finger/ear anomalies reported in x2 patients (PMID 26387593; 30950205)- unlikely to be detected antenatally and one of the reported patients (30950205) had x2 chromosome deletions, one of which involved LRP6 and multiple other genes.

---

PMID: 34306029 Huang et al 2021 - Heterozygous LRP6: c.2570G > A (p.R857H), harbored by six members of a Chinese family, including 4 with tooth agenesis. Sparse hair another phenotypic feature.

PMID: 33164649 Yu et al 2021 - identified 4 novel LRP6 heterozygous mutations in 4 of 77 oligodontia patients. One patient with a nonsense paternally inherited variant had a hypohidrotic ectodermal dysplasia phenotype - no antenatal features, father had oligodontia. Supportive functional evidence

PMID: 29500247 Basha et al 2018 - Nonsense LRP6 variant identified in a family with cleft lip/palate. Proband had bilateral cleft lip and palate with missing upper lateral incisors, mother had bilateral cleft lip. x1 unaffected brother but family members not reassessed for oligodontia after variant identified.

PMID: 28813618 Dinckan et al 2018 - heterozygous splice site LRP6 variant identified in 1 family with isolated tooth agenesis. Affected family members also had mild periocular hyperpigmentation and hypoplastic alae nasi - thought to be unrelated to phenotype

PMID: 26963285 Ockeloen et al 2016 - frameshift variant identified in patient with tooth agenesis and orofacial clefting - boy born with bilateral cleft lip, L) sided cleft of the alveolus and complete cleft of the hard and soft palate. Also noted to have growth retardation, hypermetropia and small median alveolar manibular cleft. Maternal relatives with variant had severe tooth agenesis but no clefting. Canonical splice site variant identified in a patient with isolated severe tooth agenesis. Targeted resequencing showed statistically significant enrichment of unique LRP6 variants in tooth agenesis patients (7/67 versus 13/706 controls), not orofacial clefting cohort. 4/7 of these patients required growth hormone therapy and 3/7 had clinodactyly in addition to dental anomalies.

PMID: 26387593 – Massink et al 2015 - x4 LoF heterozygous LRP6 variants identified in 4 unrelated families with isolated severe tooth agenesis. All affected members of one family showed minor anatomical variation of the ear and underdevelopment of the thumb

PMID: 30950205 Ross et al 2019 - Proband with oligodontia and thrombocytopenia, also had mild finger and ear anomalies. Array revealed an interstitial loss of 150 kb in 8p23.1 encompassing MCPH1 and ANGPT2 and an interstitial loss of 290 kb in 12p13.2 encompassing ETV6, BCL2L14 and LRP6.
Sources: Literature
Fetal anomalies v0.3140 INTS1 Krithika Murali gene: INTS1 was added
gene: INTS1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: INTS1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: INTS1 were set to 28542170; 30622326; 31428919
Phenotypes for gene: INTS1 were set to Neurodevelopmental disorder with cataracts, poor growth, and dysmorphic facies - MIM#618571
Review for gene: INTS1 was set to GREEN
Added comment: PMID: 28542170 Oegema et al 2017 - 3 unrelated individuals with syndromic ID of Dutch ancestry showed the same homozygous truncating INTS1 mutation - 1/3 Cleft palate/lip, 1/3 renal malformation

PMID: 30622326 – Krall et al 2019 - 5 patients from 4 families with biallelic sequence variants in INTS1. The patients manifested absent or severely limited speech, an abnormal gait, hypotonia and cataracts. Other phenotypic features included:
o Micropthalmia – 2/5
o Frontal bossing 2/5
o Hypertelorism – 5/5
o Microretrognathia – 4/5
o Renal malformation 2/5


PMID: 31428919 – Zhang et al 2020 - 2 Chinese siblings with ID found to have INTST1 compound het variants, both had cataracts, facial dysmorphism, short stature, severe ID and anomalous genitalia
Sources: Literature
Fetal anomalies v0.3140 FTO Krithika Murali gene: FTO was added
gene: FTO was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FTO was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FTO were set to 19559399; 26378117
Phenotypes for gene: FTO were set to Growth retardation, developmental delay, facial dysmorphism - MIM#612938; multiple congenital malformations
Review for gene: FTO was set to AMBER
Added comment: Biallelic variants associated with syndromic ID reported in 2 unrelated families.

PMID: 26378117 Daoud et al 2016 - homozygous missense variant identified in a female proband. 3rd child to consanguineous Tunisian parents. Proband also carried a paternally inherited balanced translocation. Antenatal USS identified IUGR. Postnatal Echo showed PDA and hypertrabeculation of LV apex.

PMID 19559399 Boissel et al 2009 - homozygous missense variant identified in 9 affected individuals from a consanguineous Palestinian Arab family. Phenotypic features identified most pertinent to the prenatal setting include: 3/7 IUGR, 7/7 retrognathia, congenital heart disease 6/8, lissencephaly 3/8, hypertrophic cardiomyopathy 4/8, hydrocephalus 4/8, cleft palate/bifid uvula 3/6.
Sources: Literature
Fetal anomalies v0.3140 COL9A3 Krithika Murali gene: COL9A3 was added
gene: COL9A3 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: COL9A3 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: COL9A3 were set to 33570243; 31090205; 30450842; 25381065; 24273071; 15551337
Phenotypes for gene: COL9A3 were set to Epiphyseal dysplasia, multiple, 3, with or without myopathy - MIM#600969; Stickler syndrome
Review for gene: COL9A3 was set to GREEN
Added comment: 6 patients from 4 families reported with biallelic variants associated with a Stickler syndrome like phenotype. All of these cases characterised by the absence of cleft palate, which is noted more commonly in other autosomal dominant forms of Stickler syndrome.

Potential antenatally detectable features described with biallelic COL9A3 variants include fetal growth restriction (1/6), midface hypoplasia (6/6), tibial and femoral bowing (1/6)

PMID 33570243 Markova et al 2021 - report a patient with novel Class 4 compound heterozygous COL9A3 variants confirmed to be in trans. Antenatal USS identified fetal growth restriction in the third trimester. Examination findings by clinical geneticist aged 2 provided, including dysmorphic facial features noted - slightly flattened nasal bridge, small nose, mild mid-facial hypoplasia, high palate.

PMID 31090205 – Nixon et al 2019 - homozygous COL9A3 variant identified in proband, consanguineous family. Antenatal phenotype not provided, mid-facial hypoplasia noted.

PMID: 30450842 – Hanson-Kahn et al 2018 - proband homozygous for LoF COL9A3 variants.
Phenotypic features included moderate to severe sensorineural hearing loss, high myopia, mid-face hypoplasia and both tibial and femoral bowing at birth.

PMID 24273071 Faletra et al 2014 - first reported family with AR COL9A3 associated Stickler syndrome due to homozygous LoF variants. 3 siblings with hearing loss, midface hypoplasia, high myopia, variable severity ID from consanguineous Moroccan family.

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Variants in COL9A3 have previously been associated with autosomal dominant multiple epiphyseal dysplasia, susceptibility to an intervertebral disc disease, and hearing loss. Generally milder phenotype than individuals with biallelic variants. However, PMID 33633367 Nash et al 2021 - report 2 families with heterozygous COL9A3 variants with a more severe Stickler-like phenotype including severe peripheral lattice vitreoretinal abnormalities and mild/moderate sensorineural hearing loss in some cases. No antenatal information provided
Sources: Literature
Fetal anomalies v0.3140 ANKRD17 Krithika Murali gene: ANKRD17 was added
gene: ANKRD17 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ANKRD17 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ANKRD17 were set to 33909992
Phenotypes for gene: ANKRD17 were set to Chopra-Amiel-Gordon syndrome - MIM#619504; multiple congenital malformations
Review for gene: ANKRD17 was set to GREEN
Added comment: 33909992 - Chopra et al 2021 reported 34 individuals from 33 families with a syndromic ID

Multiple cases with antenatal anomalies or features detectable antenatally reported
- 3/34 with cleft lip and/or palate (including 2 with Pierre Robin sequence)
- 1/34 retrognathia
- 5/34 renal anomalies including 3 with unilateral renal agenesis and 1 with antenatal diagnosis of horseshoe kidney
- 2/34 microcephaly
- 4/34 macrocephaly (1 noted on 37/40 antenatal USS to have macrocephaly and enlarged cisterna magna, 1 also had NSD1 variant)
- 5/34 IUGR/fetal growth concerns
-1/34 with VSD
Sources: Literature
Fetal anomalies v0.3140 ACBD5 Krithika Murali gene: ACBD5 was added
gene: ACBD5 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ACBD5 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACBD5 were set to 27799409; 23105016; 33427402; 34668366
Phenotypes for gene: ACBD5 were set to Retinal dystrophy with leukodystrophy - MIM#618863
Review for gene: ACBD5 was set to RED
Added comment: Biallelic ACBD5 variants cause impairment of very long-chain fatty acid metabolism. Patients have retinal dystrophy and leukodystrophy. Other features include ataxia, spastic paraparesis, developmental delay and facial dysmorphism. One patient with cleft palate reported but this may be an incidental finding and not related to this condition. No other antenatal features reported.

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PMID 27799409 Ferdinandusse et al 2017 - patient born full-term with cleft palate, progressive leukodystrophy, ataxia, retinal dystrophy and facial dysmorphism

PMID 23105016 Abu-Safieh et al 2013 - limited phenotypic information, reported 3 siblings with homozygous splice site ACBD5 variants with spastic paraparesis and leukodystrophy.

PMID: 33427402 Bartlett et al 2020 - 36 year old F proband born at term after an uncomplicated pregnancy, normal growth parameters.

PMID: 34668366 Gorukmez et al 2021 - x2 siblings with homozygous variant – no antenatal features reported
Sources: Literature
Fetal anomalies v0.3112 SPINT2 Zornitza Stark Phenotypes for gene: SPINT2 were changed from Diarrhea 3, secretory sodium, congenital, syndromic - MIM#270420; congenital secretory sodium diarrhea 3 - MONDO0010036 to Diarrhoea 3, secretory sodium, congenital, syndromic - MIM#270420; congenital secretory sodium diarrhea 3 - MONDO#0010036
Fetal anomalies v0.3111 SPINT2 Zornitza Stark reviewed gene: SPINT2: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Diarrhoea 3, secretory sodium, congenital, syndromic - MIM#270420, congenital secretory sodium diarrhea 3 - MONDO#0010036; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.3106 SPINT2 Krithika Murali reviewed gene: SPINT2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33029133, 29575628, 28716867, 24142340, 30445423, 19185281, 20009592, 24142340; Phenotypes: Diarrhea 3, secretory sodium, congenital, syndromic - MIM#270420, congenital secretory sodium diarrhea 3 - MONDO#0010036; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.3106 SPINT2 Krithika Murali gene: SPINT2 was added
gene: SPINT2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: SPINT2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SPINT2 were set to 19185281; 20009592; 24142340; 30445423; 33547739; 33374714; 33029133
Phenotypes for gene: SPINT2 were set to Diarrhea 3, secretory sodium, congenital, syndromic - MIM#270420; congenital secretory sodium diarrhea 3 - MONDO0010036
Fetal anomalies v0.3084 PNPLA6 Krithika Murali gene: PNPLA6 was added
gene: PNPLA6 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: PNPLA6 were set to 35069422; 33818269; 25299038; 33210227; 33141049; 32758583; 32586184
Phenotypes for gene: PNPLA6 were set to Oliver-McFarlane syndrome - MIM#275400
Review for gene: PNPLA6 was set to AMBER
Added comment: Heterogenous group of neurodegenerative conditions associated with biallelic PNPLA6 gene variants with childhood or adult onset symptoms. Oliver-McFarlane syndrome (OMFS) though is a rare congenital disorder characterised by trichomegaly, severe chorioretinal atrophy and multiple pituitary hormone deficiencies. Congenital hypogonadism is present in half of patients. Low birth weight, preterm delivery and being small for gestational age has been reported as a feature of OMFS. One case of microcephaly has been reported. Overall, limited prenatal phenotypic information for all reported cases of OMFS but associated growth restriction has the potential to be detected antenatally.

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33818269 - report two unrelated patients with Oliver McFarlane syndrome with biallelic PNPLA6 variants who were born pre-term and small for gestational age.

32758583 Liu et al 2020 - report one boy with Oliver McFarlane syndrome diagnosed with microcephaly and small for gestational age after delivery at 35 weeks.
Sources: Literature
Fetal anomalies v0.3022 PLAA Zornitza Stark changed review comment from: NDMSBA is an autosomal recessive neurodevelopmental disorder characterized by infantile onset of progressive microcephaly and spasticity and severe global developmental delay resulting in profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy. Brain imaging may show myelinating abnormalities and white matter lesions consistent with a leukoencephalopathy, as well as structural anomalies, including thin corpus callosum, gyral abnormalities, and cerebral or cerebellar atrophy.

At least 5 families reported.; to: NDMSBA is an autosomal recessive neurodevelopmental disorder characterized by infantile onset of progressive microcephaly and spasticity and severe global developmental delay resulting in profound mental retardation and severely impaired or absent motor function. More variable features include seizures and optic atrophy. Brain imaging may show myelinating abnormalities and white matter lesions consistent with a leukoencephalopathy, as well as structural anomalies, including thin corpus callosum, gyral abnormalities, and cerebral or cerebellar atrophy.

At least 5 families reported. Mouse model.
Fetal anomalies v0.3018 PIGY Zornitza Stark Phenotypes for gene: PIGY were changed from Glycosylphosphatidylinositol deficiency to Hyperphosphatasia with mental retardation syndrome 6, MIM# 616809
Fetal anomalies v0.2994 WDR62 Seb Lunke Phenotypes for gene: WDR62 were changed from MICROCEPHALY CORTICAL MALFORMATIONS AND MENTAL RETARDATION to Microcephaly 2, primary, autosomal recessive, with or without cortical malformations, MIM# 604317; MONDO:0011435
Fetal anomalies v0.2957 NSUN2 Zornitza Stark Phenotypes for gene: NSUN2 were changed from AUTOSOMAL- RECESSIVE INTELLECTUAL DISABILITY MRT5 to Mental retardation, autosomal recessive 5, MIM# 611091
Fetal anomalies v0.2936 ST3GAL3 Zornitza Stark Phenotypes for gene: ST3GAL3 were changed from MENTAL RETARDATION, AUTOSOMAL RECESSIVE 12 to Mental retardation, autosomal recessive 12 MIM# 611090; Developmental and epileptic encephalopathy 15, MIM# 615006
Fetal anomalies v0.2933 ST3GAL3 Zornitza Stark edited their review of gene: ST3GAL3: Changed rating: RED; Changed phenotypes: Mental retardation, autosomal recessive 12 MIM# 611090, Developmental and epileptic encephalopathy 15, MIM# 615006
Fetal anomalies v0.2840 MFRP Alison Yeung changed review comment from: Bi-allelic variants in this gene associated with posterior microphthalmia with retinitis pigmentosa, foveoschisis, and optic disc drusen. Ocular abnormalities not detectable on fetal US and no association with extra-ocular fetal anomalies.; to: Bi-allelic variants in this gene associated with posterior microphthalmia with retinitis pigmentosa, foveoschisis, and optic disc drusen. Ocular abnormalities not detectable on fetal US and no association with extra-ocular fetal anomalies.
Fetal anomalies v0.2839 IARS Alison Yeung Phenotypes for gene: IARS were changed from Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, 617093 to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, OMIM# 617093
Fetal anomalies v0.2838 IARS Alison Yeung reviewed gene: IARS: Rating: GREEN; Mode of pathogenicity: None; Publications: 27426735, 27891590; Phenotypes: Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, MIM#617093; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.2816 TSPAN7 Zornitza Stark Phenotypes for gene: TSPAN7 were changed from MENTAL RETARDATION X-LINKED TYPE 58 to Intellectual developmental disorder, X-linked 58, MIM# 300210
Fetal anomalies v0.2808 MEF2C Zornitza Stark Phenotypes for gene: MEF2C were changed from MENTAL RETARDATION-STEREOTYPIC MOVEMENTS-EPILEPSY AND/OR CEREBRAL MALFORMATIONS to Mental retardation, stereotypic movements, epilepsy, and/or cerebral malformations, MIM# 613443; MONDO:0013266
Fetal anomalies v0.2772 LRP5 Zornitza Stark Phenotypes for gene: LRP5 were changed from HIGH BONE MASS TRAIT; ENDOSTEAL HYPEROSTOSIS WORTH TYPE; VITREORETINOPATHY EXUDATIVE TYPE 4; OSTEOPETROSIS AUTOSOMAL DOMINANT TYPE 1; OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME to Osteoporosis-pseudoglioma syndrome, MIM# 259770; Polycystic liver disease 4 with or without kidney cysts, MIM# 617875
Fetal anomalies v0.2756 ERGIC1 Krithika Murali gene: ERGIC1 was added
gene: ERGIC1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: ERGIC1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ERGIC1 were set to 28317099; 34037256; 31230720
Phenotypes for gene: ERGIC1 were set to Arthrogryposis multiplex congenita 2, neurogenic type; OMIM # 208100
Review for gene: ERGIC1 was set to GREEN
Added comment: Recent Panelapp review by Z. Stark Oct 2021 - no new publications since

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Pehlivan et al. 2019 (PMID:31230720) identified the third case of arthrogryposis in a child who harboured a previously unreported homozygous variant (c.782G>A; p.Gly261Asp) in this gene. Parents were heterozygous carriers. Functional studies were not performed.
Created: 14 Oct 2021, 7:23 a.m. | Last Modified: 14 Oct 2021, 7:23 a.m.
Panel Version: 0.9373

Reinstein et al. (2018) used WES in a large consanguineous Israeli Arab kindred consisting of 16 patients affected with the neurogenic type of arthrogryposis multiplex congenita. They identified a homozygous missense (V98E) mutation in ERGIC1 gene, which segregated with the disorder in the kindred, and was not found in the ExAC database or in 212 ethnically matched controls. Functional studies of the variant and studies of patient cells were not performed. ERGIC1 encodes a cycling membrane protein which has a possible role in transport between endoplasmic reticulum and Golgi.

Marconi et al (2021) used genome sequencing in a consanguineous family with 2 affected siblings presenting congenital arthrogryposis and some facial dysmorphism. They identified a homozygous 22.6 Kb deletion encompassing the promoter and first exon of ERGIC1. mRNA quantification showed the complete absence of ERGIC1 expression in the two affected siblings and a decrease in heterozygous parents.
Sources: Literature
Sources: Literature
Fetal anomalies v0.2753 INPP5E Zornitza Stark Phenotypes for gene: INPP5E were changed from MENTAL RETARDATION-TRUNCAL OBESITY-RETINAL DYSTROPHY-MICROPENIS; JOUBERT SYNDROME TYPE 1 to Joubert syndrome 1, MIM# 213300; MONDO:0008944
Fetal anomalies v0.2737 HSD17B10 Zornitza Stark Phenotypes for gene: HSD17B10 were changed from 2-METHYL-3-HYDROXYBUTYRYL-COA DEHYDROGENASE DEFICIENCY; MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 10 to HSD10 mitochondrial disease, MIM# 300438
Fetal anomalies v0.2729 GDI1 Zornitza Stark Phenotypes for gene: GDI1 were changed from MENTAL RETARDATION X-LINKED TYPE 41; MENTAL RETARDATION X-LINKED TYPE 48 to Intellectual developmental disorder, X-linked 41 MIM#300849
Fetal anomalies v0.2712 FAT1 Krithika Murali gene: FAT1 was added
gene: FAT1 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: FAT1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAT1 were set to 30862798; 26905694; 34202629; 34013115; 33418956; 32902815
Phenotypes for gene: FAT1 were set to multiple congenital anomalies; nephropathy; ocular anomalies; hand and foot anomalies
Review for gene: FAT1 was set to GREEN
Added comment: No OMIM gene-disease association, but multiple affected individuals from unrelated families reported with biallelic FAT1 variants and syndromic features consisting of ocular anomalies, hand/foot malformations and nephropathy. Although diagnosis antenatally not yet reported, some phenotypic features are detectable antenatally.

PMID: 30862798 Larouchi et al 2019 - homozygous frameshift FAT1 variants identified in 10 affected individuals from 5 unrelated consanguineous families. The patients presented with syndromic features including ocular anomalies (ptosis, microphthalmia, coloboma, amblyopia), nephropathy (FSGS, proteinuria, haematuria), toe syndactyly and facial dysmorphism. Animal models showing that deletion of Fat1 leads to coloboma in mouse and zebrafish.

PMID 26905694 Gee et al 2016 – report recessive mutations in FAT1 in four unrelated consanguineous families with a combination of steroid-resistant nephrotic syndrome, tubular ectasia, haematuria and variable neurodevelopmental findings such ID, polymicrogyria and hydrocephalus. X1 child with pulmonary stenosis.

PMID: 34202629 Peluso et al 2021 – Homozygous FAT1 frameshift variant NM_005245.4:c.9729del identified in a child of consanguineous parents with bilateral anophthalmia and hand/foot malformations including - right split foot with 4 toes, 5 metacarpals, second toe duplication and preaxial polydactyly on the right hand. Patient also had congenital heart defects including VSD, ASD and bicuspid aortic valve. Proband also had a microarray which detected a maternally inherited 350 kb 15q26.3 duplication including OMIM morbid gene CERS3 (AR condition) and part of the OMIM morbid gene ADAMTS17 (AR condition). Mother healthy, CNV unrelated to patient’s phenotype.

PMID: 34013115 Fabretti et al 2021 – report 4 patients with biallelic FAT1 variants from 3 unrelated families with syndactyly, ophthalmologic and renal phenotype consistent with previously reported cases.

PMID: 33418956 Haug et al 2021 - Genetic analysis showed that proband with phenotypic features consistent with other reported cases was compound heterozygous for a frameshift FAT1 variant and 1.8Mb 4q35.2 del including FAT1.

PMID: 32902815 Rossanti et al 2021 – Biallelic FAT1 variants reported in a child with isolated mild proteinuria and no syndromic features
Sources: Literature
Fetal anomalies v0.2706 IGF1 Zornitza Stark Phenotypes for gene: IGF1 were changed from INSULIN-LIKE GROWTH FACTOR I DEFICIENCY to Growth retardation with deafness and mental retardation due to IGF1 deficiency, MIM # 608747
Fetal anomalies v0.2676 PAK3 Zornitza Stark Phenotypes for gene: PAK3 were changed from AGENESIS OF THE CORPUS CALLOSUM; MENTAL RETARDATION X-LINKED TYPE 30 to Mental retardation, X-linked 30/47, MIM# 300558; Agenesis of the corpus callosum
Fetal anomalies v0.2563 SOX11 Zornitza Stark Phenotypes for gene: SOX11 were changed from MENTAL RETARDATION, AUTOSOMAL DOMINANT, 27 to Coffin-Siris syndrome 9, OMIM # 615866
Fetal anomalies v0.2557 SLC6A17 Zornitza Stark Phenotypes for gene: SLC6A17 were changed from MENTAL RETARDATION, AUTOSOMAL RECESSIVE 48 to Mental retardation, autosomal recessive 48, MIM# 616269
Fetal anomalies v0.2538 SET Zornitza Stark Phenotypes for gene: SET were changed from SET syndrome to Mental retardation, autosomal dominant 58, MIM# 618106
Fetal anomalies v0.2483 ZMYND11 Zornitza Stark Phenotypes for gene: ZMYND11 were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 30, MIM# 616083
Fetal anomalies v0.2472 YAP1 Zornitza Stark Phenotypes for gene: YAP1 were changed from COLOBOMA, OCULAR, WITH OR WITHOUT HEARING IMPAIRMENT, CLEFT LIP/PALATE, AND/OR MENTAL RETARDATION to Coloboma, ocular, with or without hearing impairment, cleft lip/palate, and/or mental retardation, MIM#120433
Fetal anomalies v0.2454 USP9X Zornitza Stark Phenotypes for gene: USP9X were changed from MENTAL RETARDATION, X-LINKED 99 to Mental retardation, X-linked 99, XLR (MIM#300919) and XLD (MIM#300968)
Fetal anomalies v0.2451 USP27X Zornitza Stark Phenotypes for gene: USP27X were changed from INTELLECTUAL DISABILITY to Mental retardation, X-linked 105, MIM#300984
Fetal anomalies v0.2427 TUBGCP4 Zornitza Stark Phenotypes for gene: TUBGCP4 were changed from AUTOSOMAL-RECESSIVE MICROCEPHALY WITH CHORIORETINOPATHY. to Microcephaly and chorioretinopathy, autosomal recessive, MIM#616335
Fetal anomalies v0.2425 TTI2 Zornitza Stark Phenotypes for gene: TTI2 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Mental retardation, autosomal recessive 39 (MIM#615541); Microcephaly
Fetal anomalies v0.2408 TRIO Zornitza Stark Phenotypes for gene: TRIO were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 44, MIM# 617061
Fetal anomalies v0.2373 THOC2 Zornitza Stark Phenotypes for gene: THOC2 were changed from MENTAL RETARDATION, X-LINKED 12 to Mental retardation, X-linked 12/35 MIM#300957
Fetal anomalies v0.2370 THOC2 Zornitza Stark reviewed gene: THOC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 29851191; Phenotypes: Mental retardation, X-linked 12/35 MIM#300957; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.2354 TAF13 Zornitza Stark Phenotypes for gene: TAF13 were changed from Autosomal-Recessive Intellectual Disability and Microcephaly to Mental retardation, autosomal recessive 60, MIM# 617432; Microcephaly
Fetal anomalies v0.2343 EMC1 Zornitza Stark Phenotypes for gene: EMC1 were changed from Global Developmental Delay, Hypotonia, Scoliosis, and Cerebellar Atrophy. to Cerebellar atrophy, visual impairment, and psychomotor retardation, MIM# 616875
Fetal anomalies v0.2337 EIF2S3 Zornitza Stark changed review comment from: 9 families reported (3 had the same variant) with MEHMO syndrome (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity).; to: 9 families reported (3 had the same variant) with MEHMO syndrome (mental retardation, epileptic seizures, hypogonadism and hypogenitalism, microcephaly, and obesity).

Cleft palate also reported.
Fetal anomalies v0.2336 EEF1A2 Zornitza Stark Phenotypes for gene: EEF1A2 were changed from INFANTILE EPILEPTIC ENCEPHALOPATHY to Mental retardation, autosomal dominant 38, MIM# 616393; MONDO:0014617; Developmental and epileptic encephalopathy 33, MIM# 616409; MONDO:0014625
Fetal anomalies v0.2257 HUWE1 Zornitza Stark Phenotypes for gene: HUWE1 were changed from MENTAL RETARDATION SYNDROMIC X-LINKED TURNER TYPE to Mental retardation, X-linked syndromic, Turner type, MIM#309590
Fetal anomalies v0.2247 HIVEP2 Zornitza Stark Phenotypes for gene: HIVEP2 were changed from HIVEP2 associated syndromic developmental delay with intellectual disability to Mental retardation, autosomal dominant 43, MIM# 616977
Fetal anomalies v0.2242 HCFC1 Zornitza Stark Phenotypes for gene: HCFC1 were changed from COBALAMIN DISORDER; MENTAL RETARDATION, X-LINKED 3 to Mental retardation, X-linked 3 (methylmalonic acidaemia and homocysteinaemia, cblX type) MIM# 309541
Fetal anomalies v0.2228 GRIN2B Zornitza Stark Phenotypes for gene: GRIN2B were changed from MENTAL RETARDATION, AUTOSOMAL DOMINANT 6; AUTISM; EPILEPTIC ENCEPHALOPATHY to Mental retardation, autosomal dominant 6, MIM# 613970; Epileptic encephalopathy, early infantile, 27, MIM# 616139
Fetal anomalies v0.2139 Zornitza Stark removed gene:RETREG1 from the panel
Fetal anomalies v0.2056 LARGE1 Zornitza Stark Phenotypes for gene: LARGE1 were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A6; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B6 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 6, MIM# 613154
Fetal anomalies v0.2052 LAMA1 Zornitza Stark Phenotypes for gene: LAMA1 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; CEREBELLAR DYSPLASIA WITH CYSTS WITH OR WITHOUT RETINAL DYSTROPHY to Poretti-Boltshauser syndrome, MIM# 615960
Fetal anomalies v0.2050 LAMA1 Zornitza Stark changed review comment from: Four families with Poretti-Bolthauser syndrome identified in a cohort of 'unsolved' Joubert syndrome patients -- included due to phenotypic overlap.
Sources: Literature; to: Cerebellar abnormalities.

Four families with Poretti-Bolthauser syndrome identified in a cohort of 'unsolved' Joubert syndrome patients.

Sources: Literature
Fetal anomalies v0.2050 L1CAM Zornitza Stark Phenotypes for gene: L1CAM were changed from MENTAL RETARDATION-APHASIA-SHUFFLING GAIT-ADDUCTED THUMBS SYNDROME; PARTIAL AGENESIS OF THE CORPUS CALLOSUM; HYDROCEPHALUS DUE TO STENOSIS OF THE AQUEDUCT OF SYLVIUS; SPASTIC PARAPLEGIA X-LINKED TYPE 1 to Hydrocephalus due to aqueductal stenosis, MIM# 307000
Fetal anomalies v0.2032 KIF7 Zornitza Stark Phenotypes for gene: KIF7 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION; ACROCALLOSAL SYNDROME to Hydrolethalus syndrome 2, MIM# 614120; Acrocallosal syndrome
Fetal anomalies v0.2024 KIF11 Zornitza Stark Phenotypes for gene: KIF11 were changed from AUTOSOMAL-DOMINANT MICROCEPHALY ASSOCIATED WITH LYMPHEDEMA AND/OR CHORIORETINOPATHY to Microcephaly with or without chorioretinopathy, lymphoedema, or mental retardation, MIM# 152950; MONDO:0007918
Fetal anomalies v0.1998 KDM5C Zornitza Stark Phenotypes for gene: KDM5C were changed from MENTAL RETARDATION SYNDROMIC X-LINKED JARID1C-RELATED to Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534; MONDO:0010355
Fetal anomalies v0.1978 IGFBP7 Zornitza Stark Phenotypes for gene: IGFBP7 were changed from RETINAL ARTERIAL MACROANEURYSM WITH SUPRAVALVULAR PULMONIC STENOSIS to Retinal arterial macroaneurysm with supravalvular pulmonic stenosis MIM#614224
Fetal anomalies v0.1971 NSD2 Zornitza Stark gene: NSD2 was added
gene: NSD2 was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: NSD2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: NSD2 were set to 30345613; 31171569
Phenotypes for gene: NSD2 were set to Rauch-Steindl syndrome, MIM# 619695
Review for gene: NSD2 was set to GREEN
Added comment: 7 unrelated individuals reported with LOF variants. Gene thought to be responsible for many of the features of Wolf-Hirschorn syndrome.

Prenatal growth retardation is a feature.
Sources: Literature
Fetal anomalies v0.1938 NAA10 Zornitza Stark edited their review of gene: NAA10: Added comment: For Ogden association, PMID 34075687:
lethal X-linked. 9 males from 3 families with recurrent Ser37Pro
All presenting the distinctive and recognizable phenotype, which includes mostly postnatal growth retardation, global severe developmental delay, characteristic craniofacial features, and structural cardiac anomalies and/or arrhythmias

For non-lethal syndromic ID:
reported in 10 males and (mostly de novo) in 37 females
variants causing this are missense located along the protein and 1 truncating; Changed publications: 30842225, 24431331, 34075687; Changed phenotypes: Microphthalmia, syndromic 1, MIM# 309800 Ogden syndrome MIM#300855
Fetal anomalies v0.1933 IGFBP7 Ain Roesley reviewed gene: IGFBP7: Rating: RED; Mode of pathogenicity: None; Publications: Retinal arterial macroaneurysm with supravalvular pulmonic stenosis 614224; Phenotypes: Retinal arterial macroaneurysm with supravalvular pulmonic stenosis MIM#614224; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.1889 SLC26A3 Seb Lunke Phenotypes for gene: SLC26A3 were changed from Chloride diarrhea, congenital, Finnish type 214700 to Diarrhea 1, secretory chloride, congenital, MIM#214700
Fetal anomalies v0.1885 SLC26A3 Seb Lunke reviewed gene: SLC26A3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31325522, 31477378, 21394828; Phenotypes: Diarrhea 1, secretory chloride, congenital, MIM#214700; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.1858 KCNJ10 Zornitza Stark Phenotypes for gene: KCNJ10 were changed from SEIZURES-SENSORINEURAL DEAFNESS-ATAXIA-MENTAL RETARDATION-ELECTROLYTE IMBALANCE to SESAME syndrome (MIM#612780); Enlarged vestibular aqueduct, digenic (MIM#600791)
Fetal anomalies v0.1784 LRAT Daniel Flanagan reviewed gene: LRAT: Rating: RED; Mode of pathogenicity: None; Publications: 11381255, 18055821, 22570351, 17011878, 29973277, 24625443, 22559933, 31448181; Phenotypes: Leber congenital amaurosis 14 MIM#613341, Retinal dystrophy, early-onset severe MIM#613341, Retinitis pigmentosa, juvenile MIM#613341; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.1703 CLTC Zornitza Stark Phenotypes for gene: CLTC were changed from Fetal growth restriction; Mental retardation, autosomal dominant 56, OMIM:617854; Fetal akinesia to Mental retardation, autosomal dominant 56, MIM# 617854
Fetal anomalies v0.1680 CC2D1A Zornitza Stark Phenotypes for gene: CC2D1A were changed from MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 3 to Mental retardation, autosomal recessive 3, MIM# 608443
Fetal anomalies v0.1678 CC2D1A Zornitza Stark reviewed gene: CC2D1A: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal recessive 3, MIM# 608443; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.1672 C2orf71 Zornitza Stark Phenotypes for gene: C2orf71 were changed from RETINITIS PIGMENTOSA 54 to Retinitis pigmentosa 54, MIM# 613428
Fetal anomalies v0.1671 C2orf71 Zornitza Stark reviewed gene: C2orf71: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Retinitis pigmentosa 54, MIM# 613428; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.1671 SETBP1 Zornitza Stark Phenotypes for gene: SETBP1 were changed from DEVELOPMENTAL AND EXPRESSIVE LANGUAGE DELAY, MIM#616078; SCHINZEL-GIEDION MIDFACE RETRACTION SYNDROME, MIM#269150 to Schinzel-Giedion midface retraction syndrome, MIM# 269150
Fetal anomalies v0.1669 SETBP1 Zornitza Stark reviewed gene: SETBP1: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Schinzel-Giedion midface retraction syndrome, MIM# 269150; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.1662 SETBP1 Seb Lunke Phenotypes for gene: SETBP1 were changed from DEVELOPMENTAL AND EXPRESSIVE LANGUAGE DELAY; SCHINZEL-GIEDION MIDFACE RETRACTION SYNDROME to DEVELOPMENTAL AND EXPRESSIVE LANGUAGE DELAY, MIM#616078; SCHINZEL-GIEDION MIDFACE RETRACTION SYNDROME, MIM#269150
Fetal anomalies v0.1652 BRWD3 Zornitza Stark Phenotypes for gene: BRWD3 were changed from MENTAL RETARDATION X-LINKED TYPE 93 to tellectual developmental disorder, X-linked 93, MIM# 300659
Fetal anomalies v0.1642 AUTS2 Zornitza Stark changed review comment from: Mental retardation, autosomal dominant 26, MIM#615834; to: Low birth weight and microcephaly reported.
Fetal anomalies v0.1613 VLDLR Zornitza Stark Phenotypes for gene: VLDLR were changed from CEREBELLAR ATAXIA MENTAL RETARDATION AND DYSEQUILIBRIUM SYNDROME TYPE 1 to Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, MIM# 224050
Fetal anomalies v0.1611 VLDLR Alison Yeung reviewed gene: VLDLR: Rating: GREEN; Mode of pathogenicity: None; Publications: 16080122, 18326629, 10380922; Phenotypes: Cerebellar hypoplasia and mental retardation with or without quadrupedal locomotion 1, MIM# 224050; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Fetal anomalies v0.1608 FLVCR2 Zornitza Stark edited their review of gene: FLVCR2: Added comment: The proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome is a (usually) prenatally lethal disorder characterized by hydranencephaly, a distinctive glomerular vasculopathy in the central nervous system and retina, and diffuse ischemic lesions of the brain stem, basal ganglia, and spinal cord with calcifications. It is usually diagnosed by ultrasound between 26 and 33 weeks' gestation.

At least 5 unrelated families reported.; Changed rating: GREEN; Changed publications: 30712878, 20206334, 20518025, 20690116, 25677735; Changed phenotypes: Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome, MIM# 225790
Fetal anomalies v0.1602 FKTN Zornitza Stark Phenotypes for gene: FKTN were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C4; CARDIOMYOPATHY DILATED TYPE 1X; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITHOUT MENTAL RETARDATION TYPE B4; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A4 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4 253800
Fetal anomalies v0.1600 FKRP Zornitza Stark Phenotypes for gene: FKRP were changed from MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A5; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH OR WITHOUT MENTAL RETARDATION TYPE B5; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C5 to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 5 613153
Fetal anomalies v0.1584 FGD1 Zornitza Stark Phenotypes for gene: FGD1 were changed from AARSKOG-SCOTT SYNDROME to Aarskog-Scott syndrome, MIM # 305400; Mental retardation, X-linked syndromic 16, MIM# 305400
Fetal anomalies v0.1511 LINS1 Zornitza Stark Phenotypes for gene: LINS1 were changed from AUTOSOMAL RECESSIVE MENTAL RETARDATION to Mental retardation, autosomal recessive 27 (MIM#614340); autosomal recessive intellectual disability (MIM#614340)
Fetal anomalies v0.1483 OPHN1 Zornitza Stark Phenotypes for gene: OPHN1 were changed from Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, 300486 to Intellectual developmental disorder, X-linked syndromic, Billuart type (MIM#300486)
Fetal anomalies v0.1469 LINS1 Daniel Flanagan reviewed gene: LINS1: Rating: AMBER; Mode of pathogenicity: None; Publications: 23773660, 21937992, 32499722, 28181389; Phenotypes: Mental retardation, autosomal recessive 27 (MIM#614340), autosomal recessive intellectual disability (MIM#614340); Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.1467 AK2 Zornitza Stark Phenotypes for gene: AK2 were changed from RETICULAR DYSGENESIS to Reticular dysgenesis, MIM# 267500; MONDO:0009973
Fetal anomalies v0.1465 AK2 Zornitza Stark reviewed gene: AK2: Rating: RED; Mode of pathogenicity: None; Publications: 19043416, 19043417; Phenotypes: Reticular dysgenesis, MIM# 267500, MONDO:0009973; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.1464 AIPL1 Zornitza Stark Phenotypes for gene: AIPL1 were changed from LEBER CONGENITAL AMAUROSIS 4 to Leber congenital amaurosis 4, 604393; Cone-rod dystrophy, 604393; Retinitis pigmentosa, juvenile, 604393
Fetal anomalies v0.1461 AIPL1 Zornitza Stark reviewed gene: AIPL1: Rating: RED; Mode of pathogenicity: None; Publications: 10615133; Phenotypes: Leber congenital amaurosis 4, 604393, Cone-rod dystrophy, 604393, Retinitis pigmentosa, juvenile, 604393; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.1453 AFF2 Zornitza Stark Phenotypes for gene: AFF2 were changed from FRAGILE X-E MENTAL RETARDATION SYNDROME to Mental retardation, X-linked, FRAXE type 309548
Fetal anomalies v0.1411 CRADD Zornitza Stark Phenotypes for gene: CRADD were changed from Megalencephaly with Variant Lissencephaly to Mental retardation, autosomal recessive 34, with variant lissencephaly, MIM# 614499
Fetal anomalies v0.1395 COL4A3BP Zornitza Stark Phenotypes for gene: COL4A3BP were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 34, MIM# 616351
Fetal anomalies v0.1386 ZBTB18 Zornitza Stark Phenotypes for gene: ZBTB18 were changed from ZBTB18 syndrome to Mental retardation, autosomal dominant 22, MIM# 612337; Intellectual disability; microcephaly; corpus callosum abnormalities
Fetal anomalies v0.1383 ZBTB18 Zornitza Stark reviewed gene: ZBTB18: Rating: GREEN; Mode of pathogenicity: None; Publications: 29573576; Phenotypes: Mental retardation, autosomal dominant 22, MIM# 612337; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.1241 FOXG1 Ain Roesley reviewed gene: FOXG1: Rating: GREEN; Mode of pathogenicity: None; Publications: 28661489; Phenotypes: Rett syndrome, congenital variant MIM#613454; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.1220 CHRNA3 Zornitza Stark changed review comment from: Five individuals from three unrelated families.; to: Five individuals from three unrelated families.

Onset is in utero or early childhood.

Affected individuals have impaired neuronal bladder and ureteral innervation causing coordination defects that result in secondary structural defects of the renal system, including hydronephrosis, vesicoureteral reflux (VUR), and small kidneys, that may result in chronic kidney disease as well as recurrent urinary tract infections (UTIs). Surgical treatment of VUR is not effective. Most individuals also have additional autonomic features, most commonly impaired pupillary reflex and sometimes orthostatic hypotension.
Fetal anomalies v0.1183 CD96 Zornitza Stark changed review comment from: Intellectual disability is part of the phenotype. However, note one reported case ascribes causality based on translocation breakpoint, leaving only one other molecularly confirmed case with a missense variant. It is concerning no further cases have been reported, including in ClinVar, and no functional evidence is available.; to: The C syndrome, also known as Opitz trigonocephaly syndrome, is a malformation syndrome characterized by trigonocephaly, severe mental retardation, hypotonia, variable cardiac defects, redundant skin, and dysmorphic facial features, including upslanted palpebral fissures, epicanthal folds, depressed nasal bridge, and low-set, posteriorly rotated ears.

However, note one reported case ascribes causality based on translocation breakpoint, leaving only one other molecularly confirmed case with a missense variant. It is concerning no further cases have been reported, including in ClinVar, and no functional evidence is available.
Fetal anomalies v0.1183 CD151 Zornitza Stark Phenotypes for gene: CD151 were changed from NEPHROPATHY WITH PRETIBIAL EPIDERMOLYSIS BULLOSA AND DEAFNESS to Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057
Fetal anomalies v0.1180 CD151 Zornitza Stark reviewed gene: CD151: Rating: RED; Mode of pathogenicity: None; Publications: 15265795, 29138120; Phenotypes: Nephropathy with pretibial epidermolysis bullosa and deafness, MIM#609057; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.1160 CAMTA1 Zornitza Stark Phenotypes for gene: CAMTA1 were changed from CEREBELLAR ATAXIA, NONPROGRESSIVE, WITH MENTAL RETARDATION to Cerebellar ataxia, nonprogressive, with mental retardation (614756 AD)
Fetal anomalies v0.1156 CAMK2B Zornitza Stark Phenotypes for gene: CAMK2B were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 54, MIM# 617799
Fetal anomalies v0.1154 CAMK2A Zornitza Stark Phenotypes for gene: CAMK2A were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal recessive 63 MIM#618095; Mental retardation, autosomal dominant 53 MIM#617798
Fetal anomalies v0.1150 CAMK2A Zornitza Stark reviewed gene: CAMK2A: Rating: RED; Mode of pathogenicity: None; Publications: 32600977, 29784083, 29560374; Phenotypes: Mental retardation, autosomal recessive 63 MIM#618095, Mental retardation, autosomal dominant 53 MIM#617798; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Fetal anomalies v0.1114 BLOC1S6 Zornitza Stark changed review comment from: Same homozygous variant identified in two individuals with HPS, however, note that one of the articles has been retracted due to some of the data having been falsified. Another individual reported in 32245340 but pigmentary and platelet abnormalities only.

Presentation for HPS in general is post-natal.; to: Same homozygous variant identified in two individuals with HPS, however, note that one of the articles has been retracted due to some of the data having been falsified. Another individual reported in 32245340 but pigmentary and platelet abnormalities only.

Presentation of HPS in general is post-natal.
Fetal anomalies v0.1091 DYRK1A Zornitza Stark Phenotypes for gene: DYRK1A were changed from MENTAL RETARDATION AUTOSOMAL DOMINANT TYPE 7 to Mental retardation, autosomal dominant 7, MIM# 614104
Fetal anomalies v0.1088 DYRK1A Zornitza Stark reviewed gene: DYRK1A: Rating: GREEN; Mode of pathogenicity: None; Publications: 25707398; Phenotypes: Mental retardation, autosomal dominant 7, MIM# 614104; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.1086 DYNC1H1 Zornitza Stark Phenotypes for gene: DYNC1H1 were changed from SPINAL MUSCULAR ATROPHY, LOWER EXTREMITY-PREDOMINANT, AD; SEVERE ID WITH NEURONAL MIGRATION DISORDER to Charcot-Marie-Tooth disease, axonal, type 20, MIM# 614228; Mental retardation, autosomal dominant 13, MIM# 614563; Spinal muscular atrophy, lower extremity-predominant 1, MIM# 158600
Fetal anomalies v0.1079 DPM1 Zornitza Stark changed review comment from: PMID: 16641202 - 2 siblings of consanguineous parents. One patient showed retarded motor skills at 1, 2 and 4 years old, with distal myopathy present at 3 years of age. The younger sister presented at 7 weeks of age with generalized hypotonia. Both had normal CK levels. Both siblings were progressively microcephalic.

PMID: 10642602 - 2 chet siblings with hypotonia within the first year of life. Both had elevated CK. Both siblings were progressively microcephalic

PMID: 10642597 - 2 unrelated patients. One had profound hypotonia at 3 years of age. The other patient was markedly hypotonic in infancy. Both were microcephalic and hd elevated CK levels.; to: PMID: 16641202 - 2 siblings of consanguineous parents. One patient showed retarded motor skills at 1, 2 and 4 years old, with distal myopathy present at 3 years of age. The younger sister presented at 7 weeks of age with generalized hypotonia. Both had normal CK levels. Both siblings were progressively microcephalic.

PMID: 10642602 - 2 chet siblings with hypotonia within the first year of life. Both had elevated CK. Both siblings were progressively microcephalic

PMID: 10642597 - 2 unrelated patients. One had profound hypotonia at 3 years of age. The other patient was markedly hypotonic in infancy. Both were microcephalic and hd elevated CK levels.

Contractures also reported.
Fetal anomalies v0.998 NALCN Seb Lunke Phenotypes for gene: NALCN were changed from HYPOTONIA, INFANTILE, WITH PSYCHOMOTOR RETARDATION AND CHARACTERISTIC FACIES; CONGENITAL CONTRACTURES OF THE LIMBS AND FACE, HYPOTONIA, AND DEVELOPMENTAL DELAY; SEVERE HYPOTONIA, SPEECH IMPAIRMENT, AND COGNITIVE DELAY to Congenital contractures of the limbs and face, hypotonia, and developmental delay (MIM#616266); Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 (MIM#615419)
Fetal anomalies v0.957 MCIDAS Krithika Murali gene: MCIDAS was added
gene: MCIDAS was added to Fetal anomalies. Sources: Literature
Mode of inheritance for gene: MCIDAS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MCIDAS were set to 32802948; 25048963; 30237576
Phenotypes for gene: MCIDAS were set to Hydrocephalus; Arachnoid cyst; Choroid plexus hyperplasia; Ciliary dyskinesia, primary, 42 - #618695
Review for gene: MCIDAS was set to GREEN
Added comment: PMID 30237576 - Patient 17-1170 (Supplementary Table) Homozygous splice site variant in a child with progressive bronchiectasis, short stature and non-obstructive hydrocephalus on imaging.

PMID 25048963 - 3 different homozygous variants reported in 4 unrelated families. Situs invertus not observed in any of the 9 individuals reported. Functional studies showed reduction of cilia. None of the variants identified were observed in gnomAD at unexpected frequency for a recessive condition.

PMID 32802948 - Retrospective cohort study for 7 consecutive patients diagnosed with MCIDAS by the Leicester UK national PCD diagnostic laboratory. MRI-B showed that all 7 patients demonstrated choroid plexus hyperplasia, arachnoid cysts, hydrocephalus. x1
diagnosed antenatally with communicating hydrocephalus with a sibling who had increasing head circumference noted in infancy and baseline ultrasound scan showing CPH with bitempoeral arachnoid cysts. Another monozygotic twin from an unrelated family had seizures which self-resolved with D7 of life cranial U/S reported as within normal limits although mild dilatation of posterior horns of both lateral ventricles were noted. Both MZ twins had hydrocephalus diagnosed on MRI-B age 16 pre-lung transplant. Potential for younger age of ascertainment with earlier use of MRI-B.
Sources: Literature
Fetal anomalies v0.957 NALCN Daniel Flanagan reviewed gene: NALCN: Rating: GREEN; Mode of pathogenicity: None; Publications: 25683120, 23749988, 24075186; Phenotypes: Congenital contractures of the limbs and face, hypotonia, and developmental delay (MIM#616266), Hypotonia, infantile, with psychomotor retardation and characteristic facies 1 (MIM#615419); Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.952 AP4S1 Zornitza Stark changed review comment from: Spastic quadriplegia-52 is an autosomal recessive neurodevelopmental disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity and severe mental retardation with poor or absent speech development. More than 10 families reported and a zebrafish model.; to: Spastic quadriplegia-52 is an autosomal recessive neurodevelopmental disorder characterized by neonatal hypotonia that progresses to hypertonia and spasticity and severe ID with poor or absent speech development. More than 10 families reported and a zebrafish model.

Microcephaly is a feature.
Fetal anomalies v0.935 GNB1 Zornitza Stark Phenotypes for gene: GNB1 were changed from Mental retardation, autosomal dominant 42 OMIM:616973; intellectual disability, autosomal dominant 42 MONDO:0014855 to Intellectual developmental disorder, autosomal dominant 42, MIM# 616973; intellectual disability, autosomal dominant 42 MONDO:0014855
Fetal anomalies v0.818 DCX Zornitza Stark changed review comment from: Well established gene-disease association.; to: DCX mutations cause classic lissencephaly with mental retardation in hemizygous males and a milder phenotype known as subcortical band heterotopia in females, sometimes in the same family. The subcortical lamina heterotopia found in heterozygous females is also referred to as 'double cortex' (DC) syndrome. Multiple affected families reported.
Fetal anomalies v0.799 ELOVL4 Zornitza Stark Phenotypes for gene: ELOVL4 were changed from ICHTHYOSIS, SPASTIC QUADRIPLEGIA, AND MENTAL RETARDATION to Ichthyosis, spastic quadriplegia, and mental retardation MIM#614457
Fetal anomalies v0.797 ELOVL4 Zornitza Stark reviewed gene: ELOVL4: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Ichthyosis, spastic quadriplegia, and mental retardation MIM#614457; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.774 ELOVL4 Belinda Chong changed review comment from: OMIM 614457: ISQMR is a severe autosomal recessive disorder characterised by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. 5 unrelated families reported, seizures in at least 4 of the families.

OMIM 133190: Skin lesion appear shortly after birth and tend to disappear in young adulthood. In a large French-Canadian family, 14/19 individuals with a missense variant presented with erythrokeratodermia variabilis (PMID:24566826). At least two other individuals reported with erythrokeratodermia (and SCA34) as a result of a missense variant (PMID:26258735; 30065956).

OMIM 600110: Stargardt disease-3 (STGD3) is an autosomal dominant juvenile macular dystrophy with onset most commonly in the second decade of life. Fundus examination reveals macular pigmentary changes and yellow flecks. Fluorescein angiography shows macular retinal pigment epithelium (RPE) defects; to: OMIM 614457: ISQMR is a severe autosomal recessive disorder characterised by ichthyosis apparent from birth, profound psychomotor retardation with essentially no development, spastic quadriplegia, and seizures. 5 unrelated families reported, seizures in at least 4 of the families.

OMIM 133190: Skin lesion appear shortly after birth and tend to disappear in young adulthood. In a large French-Canadian family, 14/19 individuals with a missense variant presented with erythrokeratodermia variabilis (PMID:24566826). At least two other individuals reported with erythrokeratodermia (and SCA34) as a result of a missense variant (PMID:26258735; 30065956).

OMIM 600110: Stargardt disease-3 (STGD3) is an autosomal dominant juvenile macular dystrophy with onset most commonly in the second decade of life. Fundus examination reveals macular pigmentary changes and yellow flecks. Fluorescein angiography shows macular retinal pigment epithelium (RPE) defects
Fetal anomalies v0.774 ELOVL4 Belinda Chong reviewed gene: ELOVL4: Rating: GREEN; Mode of pathogenicity: None; Publications: 24566826, 26258735, 30065956, 22100072, 24571530, 33652762, 10634627, 8002834; Phenotypes: Ichthyosis, spastic quadriplegia, and mental retardation MIM#614457, Spinocerebellar ataxia 34 MIM#133190, Stargardt disease 3 MIM#600110; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Fetal anomalies v0.774 ACSL4 Zornitza Stark Phenotypes for gene: ACSL4 were changed from ALPORT SYNDROME WITH MENTAL RETARDATION MIDFACE HYPOPLASIA AND ELLIPTOCYTOSIS; MENTAL RETARDATION X-LINKED TYPE 63 to Mental retardation, X-linked 63 , MIM#300387
Fetal anomalies v0.771 ACO2 Zornitza Stark Phenotypes for gene: ACO2 were changed from INFANTILE CEREBELLAR-RETINAL DEGENERATION to Infantile cerebellar-retinal degeneration, MIM# 614559
Fetal anomalies v0.769 ACO2 Zornitza Stark reviewed gene: ACO2: Rating: AMBER; Mode of pathogenicity: None; Publications: 22405087, 25351951, 30689204, 32519519; Phenotypes: Infantile cerebellar-retinal degeneration, MIM# 614559; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.743 CWC27 Zornitza Stark Phenotypes for gene: CWC27 were changed from Retinitis pigmentosa, skeletal anomalies and intellectual disability to Retinitis pigmentosa with or without skeletal anomalies, MIM# 250410
Fetal anomalies v0.741 CWC27 Zornitza Stark reviewed gene: CWC27: Rating: GREEN; Mode of pathogenicity: None; Publications: 28285769, 31481716; Phenotypes: Retinitis pigmentosa with or without skeletal anomalies, MIM# 250410; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies v0.735 CUL4B Zornitza Stark Phenotypes for gene: CUL4B were changed from MENTAL RETARDATION SYNDROMIC X-LINKED CABEZAS TYPE to Mental retardation, X-linked, syndromic 15 (Cabezas type), MIM# 300354
Fetal anomalies v0.733 CUL4B Zornitza Stark reviewed gene: CUL4B: Rating: GREEN; Mode of pathogenicity: None; Publications: 17236139, 19377476; Phenotypes: Mental retardation, X-linked, syndromic 15 (Cabezas type), MIM# 300354; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females
Fetal anomalies v0.728 CTNNB1 Zornitza Stark Phenotypes for gene: CTNNB1 were changed from MENTAL RETARDATION, AUTOSOMAL DOMINANT 19 to Neurodevelopmental disorder with spastic diplegia and visual defects , MIM#615075
Fetal anomalies v0.725 CTCF Zornitza Stark Phenotypes for gene: CTCF were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 21 (MIM#615502)
Fetal anomalies v0.723 CTCF Zornitza Stark reviewed gene: CTCF: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Mental retardation, autosomal dominant 21 (MIM#615502); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.722 CTC1 Zornitza Stark Phenotypes for gene: CTC1 were changed from CEREBRORETINAL MICROANGIOPATHY WITH CALCIFICATIONS AND CYSTS to Cerebroretinal microangiopathy with calcifications and cysts, MIM# 612199
Fetal anomalies v0.720 CTC1 Zornitza Stark edited their review of gene: CTC1: Added comment: Cerebroretinal microangiopathy with calcifications and cysts (CRMCC), also known as Coats plus syndrome, is an autosomal recessive pleomorphic disorder characterized primarily by intracranial calcifications, leukodystrophy, and brain cysts, resulting in spasticity, ataxia, dystonia, seizures, and cognitive decline. Patients also have retinal telangiectasia and exudates (Coats disease) as well as extraneurologic manifestations, including osteopenia with poor bone healing and a high risk of gastrointestinal bleeding and portal hypertension caused by vasculature ectasias in the stomach, small intestine, and liver. Some individuals also have hair, skin, and nail changes, as well as anaemia and thrombocytopaenia.

Multiple families reported.; Changed rating: GREEN; Changed publications: 22267198
Fetal anomalies v0.649 KRIT1 Zornitza Stark Phenotypes for gene: KRIT1 were changed from CEREBRAL CAVERNOUS MALFORMATIONS TYPE 1 to Cavernous malformations of CNS and retina MIM#116860; Cerebral cavernous malformations-1 MIM#116860; Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations MIM#116860
Fetal anomalies v0.621 KAT6A Zornitza Stark Phenotypes for gene: KAT6A were changed from MENTAL RETARDATION, AUTOSOMAL DOMINANT 32 to Arboleda-Tham syndrome MIM#616268
Fetal anomalies v0.612 PAX2 Dean Phelan reviewed gene: PAX2: Rating: AMBER; Mode of pathogenicity: None; Publications: 21654726, 24676634, 31060108, 32203253; Phenotypes: Papillorenal syndrome, Renal coloboma syndrome, ventricular septal defect, skeletal deformity, ovarian teratoma, growth retardation, gout, microcephaly, developmental disorder, gonadal abnormalities; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.582 KRIT1 Ain Roesley reviewed gene: KRIT1: Rating: RED; Mode of pathogenicity: None; Publications: 34556564, 20301470; Phenotypes: Cavernous malformations of CNS and retina MIM#116860, Cerebral cavernous malformations-1 MIM#116860, Hyperkeratotic cutaneous capillary-venous malformations associated with cerebral capillary malformations MIM#116860; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes
Fetal anomalies v0.581 COL4A3BP Zornitza Stark reviewed gene: COL4A3BP: Rating: AMBER; Mode of pathogenicity: None; Publications: 25533962; Phenotypes: Mental retardation, autosomal dominant 34, MIM# 616351; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.573 COL2A1 Zornitza Stark Phenotypes for gene: COL2A1 were changed from KNIEST DYSPLASIA; SPONDYLOEPIMETAPHYSEAL DYSPLASIA STRUDWICK TYPE; PLATYSPONDYLIC LETHAL SKELETAL DYSPLASIA TORRANCE TYPE; STICKLER SYNDROME TYPE 1 NON-SYNDROMIC OCULAR; RHEGMATOGENOUS RETINAL DETACHMENT AUTOSOMAL DOMINANT; SPONDYLOEPIPHYSEAL DYSPLASIA CONGENITA; ACHONDROGENESIS TYPE 2; SPONDYLOPERIPHERAL DYSPLASIA to Collagenopathy type 2 alpha 1, MONDO:0022800
Fetal anomalies v0.546 MEIS2 Zornitza Stark reviewed gene: MEIS2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33427397, 25712757; Phenotypes: Cleft palate, cardiac defects, and mental retardation (MIM#600987); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.517 CKAP2L Zornitza Stark Phenotypes for gene: CKAP2L were changed from FILIPPI SYNDROME. SYNDACTYLY, TYPE I, WITH MICROCEPHALY AND MENTAL RETARDATION to Filippi syndrome, MIM# 272440
Fetal anomalies v0.483 IL1RAPL1 Zornitza Stark Phenotypes for gene: IL1RAPL1 were changed from MENTAL RETARDATION X-LINKED TYPE 21 to Intellectual developmental disorder, X-linked 21 MIM#300143
Fetal anomalies v0.448 ITGA6 Ain Roesley changed review comment from: At least 4 probands reported

Pyelonephrosis, Urethrovesical occlusion and Stenosis at the ureterovesical junctions are some other features in this condition; to: At least 4 probands reported

Epidermolysis bullosa with pyloric atresia (EB-PA) is characterized by fragility of the skin and mucous membranes, manifested by blistering with little or no trauma; congenital pyloric atresia; and ureteral and renal anomalies (dysplastic/multicystic kidney, hydronephrosis/hydroureter, ureterocele, duplicated renal collecting system, absent bladder).
Fetal anomalies v0.440 CHAMP1 Zornitza Stark Phenotypes for gene: CHAMP1 were changed from INTELLECTUAL DISABILITY to Mental retardation, autosomal dominant 40 (MIM#616579); microcephaly
Fetal anomalies v0.437 CHAMP1 Zornitza Stark reviewed gene: CHAMP1: Rating: GREEN; Mode of pathogenicity: None; Publications: 27148580, 26340335; Phenotypes: Mental retardation, autosomal dominant 40 (MIM#616579); Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Fetal anomalies v0.374 CASK Zornitza Stark Phenotypes for gene: CASK were changed from MENTAL RETARDATION X-LINKED CASK-RELATED; MRX WITH/WITHOUT NYSTAGMUS; FG SYNDROME TYPE 4 to FG syndrome 4, MIM# 300422; Mental retardation, with or without nystagmus, MIM# 300422; Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia, MIM# 300749
Fetal anomalies v0.371 CASK Zornitza Stark edited their review of gene: CASK: Changed rating: GREEN; Changed phenotypes: FG syndrome 4, MIM# 300422, Mental retardation, with or without nystagmus, MIM# 300422, Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia, MIM# 300749
Fetal anomalies v0.365 CA8 Zornitza Stark Phenotypes for gene: CA8 were changed from CEREBELLAR ATAXIA MENTAL RETARDATION AND DYSEQUILIBRIUM SYNDROME TYPE 3 to Cerebellar ataxia and mental retardation with or without quadrupedal locomotion 3, MIM#613227
Fetal anomalies v0.358 C8orf37 Zornitza Stark changed review comment from: Two unrelated individuals reported with BBS; note gene has an association with retinal ciliopathies.
Sources: Expert list; to: Two unrelated individuals reported with BBS; note gene has an association with retinal ciliopathies, which would not be detectable antenatally.
Sources: Expert list
Fetal anomalies v0.354 C21orf2 Zornitza Stark changed review comment from: Axial spondylometaphyseal dysplasia (SMDAX) is characterized by postnatal growth failure, including rhizomelic short stature in early childhood that evolves into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and vision rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on funduscopic examination and as cone-rod dystrophy on ERG. Radiologic hallmarks include short ribs with flared and cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora. At least 7 unrelated families reported.

New HGNC approved name is CFAP410.; to: Axial spondylometaphyseal dysplasia (SMDAX) is characterized by postnatal growth failure, including rhizomelic short stature in early childhood that evolves into short trunk in late childhood, and thoracic hypoplasia that may cause mild to moderate respiratory problems in the neonatal period and later susceptibility to airway infection. Impaired visual acuity comes to medical attention in early life and vision rapidly deteriorates. Retinal changes are diagnosed as retinitis pigmentosa or pigmentary retinal degeneration on funduscopic examination and as cone-rod dystrophy on ERG. Radiologic hallmarks include short ribs with flared and cupped anterior ends, mild spondylar dysplasia, lacy iliac crests, and metaphyseal irregularities essentially confined to the proximal femora. At least 7 unrelated families reported.

New HGNC approved name is CFAP410.

Thoracic hypoplasia is present at birth so relevant to this panel.
Fetal anomalies v0.276 B3GLCT Zornitza Stark changed review comment from: Retinal coloboma is part of the phenotype.
Sources: Expert list; to: IUGR, cleft lip/palate are part of the phenotype.
Sources: Expert list
Fetal anomalies v0.267 DDX3X Zornitza Stark Phenotypes for gene: DDX3X were changed from Intellectual disability; INTELLECTUAL DIABILITY; Mental retardation, X-linked 102, 300958 to Intellectual developmental disorder, X-linked, syndrome, Snijders Blok type MIM# 300958
Fetal anomalies v0.211 ATRX Zornitza Stark Phenotypes for gene: ATRX were changed from ALPHA-THALASSEMIA MENTAL RETARDATION SYNDROME X-LINKED NON-DELETION TYPE; MENTAL RETARDATION SYNDROMIC X-LINKED WITH HYPOTONIC FACIES SYNDROME TYPE 1 to Alpha-thalassemia/mental retardation syndrome, MIM# 301040
Fetal anomalies v0.197 ASXL1 Zornitza Stark changed review comment from: Colobomas reported.; to: Bohring-Opitz syndrome is a malformation syndrome characterized by severe intrauterine growth retardation, poor feeding, profound ID, trigonocephaly, prominent metopic suture, exophthalmos, nevus flammeus of the face, upslanting palpebral fissures, hirsutism, and flexion of the elbows and wrists with deviation of the wrists and metacarpophalangeal joints -- many of these features would be identifiable antenatally.
Fetal anomalies v0.187 ARX Zornitza Stark Phenotypes for gene: ARX were changed from AGENESIS OF THE CORPUS CALLOSUM WITH ABNORMAL GENITALIA; EPILEPTIC ENCEPHALOPATHY EARLY INFANTILE TYPE 1; PARTINGTON SYNDROME; MENTAL RETARDATION X-LINKED ARX-RELATED; LISSENCEPHALY X-LINKED TYPE 2 to Hydranencephaly with abnormal genitalia, MIM# 300215; Lissencephaly, X-linked 2, MIM# 300215
Fetal anomalies v0.185 ARX Zornitza Stark changed review comment from: X-linked lissencephaly-2 (LISX2) is a developmental disorder characterized by structural brain anomalies, early-onset intractable seizures, severe psychomotor retardation, and ambiguous genitalia. Males are severely affected and often die within the first days or months of life, whereas females may be unaffected or have a milder phenotype (Bonneau et al., 2002). LISX2 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from hydranencephaly and lissencephaly to Proud syndrome; to: X-linked lissencephaly-2 (LISX2) is a developmental disorder characterized by structural brain anomalies, early-onset intractable seizures, severe psychomotor retardation, and ambiguous genitalia. Males are severely affected and often die within the first days or months of life, whereas females may be unaffected or have a milder phenotype. LISX2 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from hydranencephaly and lissencephaly to Proud syndrome.

Variants in this gene can also cause ID/EE in the absence of congenital anomalies.
Fetal anomalies v0.185 ARX Zornitza Stark edited their review of gene: ARX: Added comment: X-linked lissencephaly-2 (LISX2) is a developmental disorder characterized by structural brain anomalies, early-onset intractable seizures, severe psychomotor retardation, and ambiguous genitalia. Males are severely affected and often die within the first days or months of life, whereas females may be unaffected or have a milder phenotype (Bonneau et al., 2002). LISX2 is part of a phenotypic spectrum of disorders caused by mutation in the ARX gene comprising a nearly continuous series of developmental disorders ranging from hydranencephaly and lissencephaly to Proud syndrome; Changed rating: GREEN; Changed publications: 14722918, 12379852, 14722918; Changed phenotypes: Hydranencephaly with abnormal genitalia, MIM# 300215, Lissencephaly, X-linked 2, MIM# 300215
Fetal anomalies v0.173 ARL6 Zornitza Stark Phenotypes for gene: ARL6 were changed from RETINITIS PIGMENTOSA TYPE 55; BARDET-BIEDL SYNDROME TYPE 3 to Bardet-Biedl syndrome 3, MIM# 600151
Fetal anomalies v0.171 ARID1B Zornitza Stark Phenotypes for gene: ARID1B were changed from COFFIN SIRIS SYNDROME; MENTAL RETARDATION, AUTOSOMAL DOMINANT 12 to Coffin-Siris syndrome 1, MIM 135900
Fetal anomalies v0.118 KMT5B Zornitza Stark Phenotypes for gene: KMT5B were changed from KMT5B syndrome to Mental retardation, autosomal dominant 51, MIM#617788
Fetal anomalies v0.111 ALMS1 Zornitza Stark changed review comment from: Overlap of clinical features of BBS: retinitis pigmentosa, deafness, obesity, and diabetes mellitus; but degree of learning difficulties is less pronounced and there is no polydactyly, or hypogonadism; to: Overlap of clinical features of BBS: retinitis pigmentosa, deafness, obesity, and diabetes mellitus; but degree of learning difficulties is less pronounced and there is no polydactyly, or hypogonadism.

Congenital anomalies are a rare feature.
Fetal anomalies v0.84 ALDH18A1 Zornitza Stark Phenotypes for gene: ALDH18A1 were changed from SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT; MENTAL RETARDATION-JOINT HYPERMOBILITY-SKIN LAXITY WITH OR WITHOUT METABOLIC ABNORMALITIES; CUTIS LAXA, AUTOSOMAL DOMINANT 3 to Cutis laxa, autosomal dominant 3, MIM# 616603; Cutis laxa, autosomal recessive, type IIIA, MIM# 219150
Fetal anomalies v0.59 ADNP Zornitza Stark Phenotypes for gene: ADNP were changed from MENTAL RETARDATION, AUTOSOMAL DOMINANT, 28 to Helsmoortel-van der Aa syndrome MIM#615873; MONDO:0014379
Fetal anomalies v0.0 ZNF711 Zornitza Stark gene: ZNF711 was added
gene: ZNF711 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ZNF711 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ZNF711 were set to MENTAL RETARDATION X-LINKED ZNF711-RELATED
Fetal anomalies v0.0 ZDHHC9 Zornitza Stark gene: ZDHHC9 was added
gene: ZDHHC9 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: ZDHHC9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ZDHHC9 were set to MENTAL RETARDATION SYNDROMIC X-LINKED ZDHHC9-RELATED
Fetal anomalies v0.0 UPF3B Zornitza Stark gene: UPF3B was added
gene: UPF3B was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: UPF3B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: UPF3B were set to MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 14
Fetal anomalies v0.0 UNC80 Zornitza Stark gene: UNC80 was added
gene: UNC80 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: UNC80 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UNC80 were set to Persistent Hypotonia, Encephalopathy, Growth Retardation, and Severe Intellectual Disability
Fetal anomalies v0.0 UBE2A Zornitza Stark gene: UBE2A was added
gene: UBE2A was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: UBE2A was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: UBE2A were set to UBE2A-RELATED X-LINKED SYNDROMIC MENTAL RETARDATION
Fetal anomalies v0.0 TUSC3 Zornitza Stark gene: TUSC3 was added
gene: TUSC3 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TUSC3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TUSC3 were set to MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 7
Fetal anomalies v0.0 TSPAN7 Zornitza Stark gene: TSPAN7 was added
gene: TSPAN7 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TSPAN7 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: TSPAN7 were set to MENTAL RETARDATION X-LINKED TYPE 58
Fetal anomalies v0.0 TNXB Zornitza Stark gene: TNXB was added
gene: TNXB was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: TNXB was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: TNXB were set to Vesicoureteral reflux 8 615963; Ehlers-Danlos syndrome due to tenascin X deficiency 606408
Fetal anomalies v0.0 SYP Zornitza Stark gene: SYP was added
gene: SYP was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: SYP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SYP were set to MENTAL RETARDATION X-LINKED SYP-RELATED
Fetal anomalies v0.0 SYNGAP1 Zornitza Stark gene: SYNGAP1 was added
gene: SYNGAP1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: SYNGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SYNGAP1 were set to MENTAL RETARDATION AUTOSOMAL DOMINANT TYPE 5; EPILEPTIC ENCEPHALOPATHY
Fetal anomalies v0.0 SLC9A6 Zornitza Stark gene: SLC9A6 was added
gene: SLC9A6 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: SLC9A6 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SLC9A6 were set to MENTAL RETARDATION SYNDROMIC X-LINKED CHRISTIANSON TYPE
Fetal anomalies v0.0 SHROOM4 Zornitza Stark gene: SHROOM4 was added
gene: SHROOM4 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: SHROOM4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SHROOM4 were set to 32565546
Phenotypes for gene: SHROOM4 were set to Stocco dos Santos X-linked mental retardation syndrome, 300434
Fetal anomalies v0.0 RETREG1 Zornitza Stark gene: RETREG1 was added
gene: RETREG1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: RETREG1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: RETREG1 were set to NEUROPATHY, HEREDITARY SENSORY AND AUTONOMIC, TYPE IIB
Fetal anomalies v0.0 RAB39B Zornitza Stark gene: RAB39B was added
gene: RAB39B was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: RAB39B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: RAB39B were set to 29152164; 20159109
Phenotypes for gene: RAB39B were set to MENTAL RETARDATION X-LINKED TYPE 72 (MRX72) +/- PARKINSONS
Fetal anomalies v0.0 PRSS12 Zornitza Stark gene: PRSS12 was added
gene: PRSS12 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: PRSS12 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PRSS12 were set to MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 1
Fetal anomalies v0.0 PRRT2 Zornitza Stark gene: PRRT2 was added
gene: PRRT2 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: PRRT2 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: PRRT2 were set to AUTOSOMAL RECESSIVE MENTAL RETARDATION; BENIGN FAMILIAL INFANTILE EPILEPSY AND INFANTILE CONVULSIONS WITH CHOREOATHETOSIS SYNDROME
Fetal anomalies v0.0 PDE6G Zornitza Stark gene: PDE6G was added
gene: PDE6G was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: PDE6G was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDE6G were set to RETINITIS PIGMENTOSA 57
Fetal anomalies v0.0 MECP2 Zornitza Stark gene: MECP2 was added
gene: MECP2 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: MECP2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: MECP2 were set to 30712880
Phenotypes for gene: MECP2 were set to MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 13; MENTAL RETARDATION SYNDROMIC X-LINKED LUBS TYPE; CHROMOSOME XQ28 DUPLICATION SYNDROME; ENCEPHALOPATHY NEONATAL SEVERE DUE TO MECP2 MUTATIONS; RETT SYNDROME (RTT)[
Fetal anomalies v0.0 KCNJ10 Zornitza Stark gene: KCNJ10 was added
gene: KCNJ10 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: KCNJ10 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KCNJ10 were set to SEIZURES-SENSORINEURAL DEAFNESS-ATAXIA-MENTAL RETARDATION-ELECTROLYTE IMBALANCE
Fetal anomalies v0.0 IQSEC2 Zornitza Stark gene: IQSEC2 was added
gene: IQSEC2 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: IQSEC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: IQSEC2 were set to MENTAL RETARDATION X-LINKED TYPE 1
Fetal anomalies v0.0 HSD17B10 Zornitza Stark gene: HSD17B10 was added
gene: HSD17B10 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: HSD17B10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: HSD17B10 were set to 2-METHYL-3-HYDROXYBUTYRYL-COA DEHYDROGENASE DEFICIENCY; MENTAL RETARDATION SYNDROMIC X-LINKED TYPE 10
Fetal anomalies v0.0 HDAC4 Zornitza Stark gene: HDAC4 was added
gene: HDAC4 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: HDAC4 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: HDAC4 were set to BRACHYDACTYLY-MENTAL RETARDATION SYNDROME
Fetal anomalies v0.0 GRIK2 Zornitza Stark gene: GRIK2 was added
gene: GRIK2 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: GRIK2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: GRIK2 were set to MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 6
Fetal anomalies v0.0 GRIA3 Zornitza Stark gene: GRIA3 was added
gene: GRIA3 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: GRIA3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: GRIA3 were set to MENTAL RETARDATION X-LINKED TYPE 94
Fetal anomalies v0.0 GDI1 Zornitza Stark gene: GDI1 was added
gene: GDI1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: GDI1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: GDI1 were set to MENTAL RETARDATION X-LINKED TYPE 41; MENTAL RETARDATION X-LINKED TYPE 48
Fetal anomalies v0.0 FTSJ1 Zornitza Stark gene: FTSJ1 was added
gene: FTSJ1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: FTSJ1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: FTSJ1 were set to MENTAL RETARDATION X-LINKED TYPE 44
Fetal anomalies v0.0 FOXP1 Zornitza Stark gene: FOXP1 was added
gene: FOXP1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: FOXP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: FOXP1 were set to MENTAL RETARDATION WITH LANGUAGE IMPAIRMENT AND AUTISTIC FEATURES
Fetal anomalies v0.0 FLVCR1 Zornitza Stark gene: FLVCR1 was added
gene: FLVCR1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: FLVCR1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FLVCR1 were set to ATAXIA, POSTERIOR COLUMN, WITH RETINITIS PIGMENTOSA
Fetal anomalies v0.0 FAM161A Zornitza Stark gene: FAM161A was added
gene: FAM161A was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: FAM161A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FAM161A were set to RETINITIS PIGMENTOSA 28
Fetal anomalies v0.0 DLG3 Zornitza Stark gene: DLG3 was added
gene: DLG3 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: DLG3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: DLG3 were set to MENTAL RETARDATION X-LINKED TYPE 90
Fetal anomalies v0.0 DEAF1 Zornitza Stark gene: DEAF1 was added
gene: DEAF1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: DEAF1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: DEAF1 were set to Autism, intellectual disability, basal ganglia dysfunction and epilepsy; MENTAL RETARDATION, AUTOSOMAL DOMINANT 24
Fetal anomalies v0.0 CRB1 Zornitza Stark gene: CRB1 was added
gene: CRB1 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CRB1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CRB1 were set to RETINITIS PIGMENTOSA-12, AUTOSOMAL RECESSIVE; LEBER CONGENITAL AMAUROSIS 8
Fetal anomalies v0.0 CC2D1A Zornitza Stark gene: CC2D1A was added
gene: CC2D1A was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: CC2D1A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CC2D1A were set to MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 3
Fetal anomalies v0.0 C2orf71 Zornitza Stark gene: C2orf71 was added
gene: C2orf71 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: C2orf71 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: C2orf71 were set to RETINITIS PIGMENTOSA 54
Fetal anomalies v0.0 BRWD3 Zornitza Stark gene: BRWD3 was added
gene: BRWD3 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: BRWD3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: BRWD3 were set to MENTAL RETARDATION X-LINKED TYPE 93
Fetal anomalies v0.0 AK2 Zornitza Stark gene: AK2 was added
gene: AK2 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: AK2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: AK2 were set to RETICULAR DYSGENESIS
Fetal anomalies v0.0 AFF2 Zornitza Stark gene: AFF2 was added
gene: AFF2 was added to Fetal anomalies. Sources: Expert Review Red,Genomics England PanelApp
Mode of inheritance for gene: AFF2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: AFF2 were set to FRAGILE X-E MENTAL RETARDATION SYNDROME
Fetal anomalies v0.0 YAP1 Zornitza Stark gene: YAP1 was added
gene: YAP1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: YAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: YAP1 were set to COLOBOMA, OCULAR, WITH OR WITHOUT HEARING IMPAIRMENT, CLEFT LIP/PALATE, AND/OR MENTAL RETARDATION
Fetal anomalies v0.0 USP9X Zornitza Stark gene: USP9X was added
gene: USP9X was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: USP9X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: USP9X were set to MENTAL RETARDATION, X-LINKED 99
Fetal anomalies v0.0 TUBGCP4 Zornitza Stark gene: TUBGCP4 was added
gene: TUBGCP4 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: TUBGCP4 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TUBGCP4 were set to 25817018
Phenotypes for gene: TUBGCP4 were set to AUTOSOMAL-RECESSIVE MICROCEPHALY WITH CHORIORETINOPATHY.
Fetal anomalies v0.0 TTI2 Zornitza Stark gene: TTI2 was added
gene: TTI2 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: TTI2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTI2 were set to AUTOSOMAL RECESSIVE MENTAL RETARDATION
Fetal anomalies v0.0 THOC2 Zornitza Stark gene: THOC2 was added
gene: THOC2 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: THOC2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: THOC2 were set to MENTAL RETARDATION, X-LINKED 12
Fetal anomalies v0.0 ST3GAL3 Zornitza Stark gene: ST3GAL3 was added
gene: ST3GAL3 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: ST3GAL3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ST3GAL3 were set to MENTAL RETARDATION, AUTOSOMAL RECESSIVE 12
Fetal anomalies v0.0 SOX11 Zornitza Stark gene: SOX11 was added
gene: SOX11 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: SOX11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOX11 were set to MENTAL RETARDATION, AUTOSOMAL DOMINANT, 27
Fetal anomalies v0.0 SMS Zornitza Stark gene: SMS was added
gene: SMS was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: SMS was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: SMS were set to Mental retardation, X-linked, Snyder-Robinson type, OMIM:309583; Syndromic X-linked intellectual disability Snyder type, MONDO:0010664
Fetal anomalies v0.0 SLC6A17 Zornitza Stark gene: SLC6A17 was added
gene: SLC6A17 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: SLC6A17 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SLC6A17 were set to MENTAL RETARDATION, AUTOSOMAL RECESSIVE 48
Fetal anomalies v0.0 SIX6 Zornitza Stark gene: SIX6 was added
gene: SIX6 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: SIX6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SIX6 were set to Optic disc anomalies with retinal and/or macular dystrophy, OMIM:212550; Colobomatous optic disc-macular atrophy-chorioretinopathy syndrome, MONDO:0008927
Fetal anomalies v0.0 RPL10 Zornitza Stark gene: RPL10 was added
gene: RPL10 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: RPL10 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: RPL10 were set to Intellectual disability, X-linked, syndromic, 35, MONDO:0030908; Mental retardation, X-linked, syndromic, 35, OMIM:300998
Fetal anomalies v0.0 PDE6H Zornitza Stark gene: PDE6H was added
gene: PDE6H was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: PDE6H was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDE6H were set to ACHROMATOPSIA; RETINAL CONE DYSTROPHY 3 PDE6H
Fetal anomalies v0.0 MSTO1 Zornitza Stark gene: MSTO1 was added
gene: MSTO1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: MSTO1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: MSTO1 were set to 28544275; 29339779; 31130378; 31604776; 28554942
Phenotypes for gene: MSTO1 were set to Myopathy, mitochondrial, and ataxia, OMIM:617675; Mitochondrial myopathy-cerebellar ataxia-pigmentary retinopathy syndrome, MONDO:0044714
Fetal anomalies v0.0 MEIS2 Zornitza Stark gene: MEIS2 was added
gene: MEIS2 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: MEIS2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: MEIS2 were set to 30055086; 27225850; 25712757; 24678003; 30291340
Phenotypes for gene: MEIS2 were set to Cardiac malformation, cleft lip/palate, microcephaly, and digital anomalies, MONDO:0010970; Cleft palate, cardiac defects, and mental retardation, OMIM:600987
Fetal anomalies v0.0 MAN1B1 Zornitza Stark gene: MAN1B1 was added
gene: MAN1B1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: MAN1B1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: MAN1B1 were set to AUTOSOMAL RECESSIVE MENTAL RETARDATION
Fetal anomalies v0.0 LINS1 Zornitza Stark gene: LINS1 was added
gene: LINS1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: LINS1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LINS1 were set to AUTOSOMAL RECESSIVE MENTAL RETARDATION
Fetal anomalies v0.0 IRX5 Zornitza Stark gene: IRX5 was added
gene: IRX5 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: IRX5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IRX5 were set to HYPERTELORISM, SEVERE, WITH MIDFACE PROMINENCE, MYOPIA, MENTAL RETARDATION, AND BONE FRAGILITY
Fetal anomalies v0.0 IGFBP7 Zornitza Stark gene: IGFBP7 was added
gene: IGFBP7 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: IGFBP7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: IGFBP7 were set to RETINAL ARTERIAL MACROANEURYSM WITH SUPRAVALVULAR PULMONIC STENOSIS
Fetal anomalies v0.0 CLTC Zornitza Stark gene: CLTC was added
gene: CLTC was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: CLTC was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CLTC were set to 33743358
Phenotypes for gene: CLTC were set to Fetal growth restriction; Mental retardation, autosomal dominant 56, OMIM:617854; Fetal akinesia
Fetal anomalies v0.0 CD151 Zornitza Stark gene: CD151 was added
gene: CD151 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: CD151 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CD151 were set to NEPHROPATHY WITH PRETIBIAL EPIDERMOLYSIS BULLOSA AND DEAFNESS
Fetal anomalies v0.0 CAMTA1 Zornitza Stark gene: CAMTA1 was added
gene: CAMTA1 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: CAMTA1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: CAMTA1 were set to CEREBELLAR ATAXIA, NONPROGRESSIVE, WITH MENTAL RETARDATION
Fetal anomalies v0.0 ACSL4 Zornitza Stark gene: ACSL4 was added
gene: ACSL4 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: ACSL4 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ACSL4 were set to ALPORT SYNDROME WITH MENTAL RETARDATION MIDFACE HYPOPLASIA AND ELLIPTOCYTOSIS; MENTAL RETARDATION X-LINKED TYPE 63
Fetal anomalies v0.0 ACO2 Zornitza Stark gene: ACO2 was added
gene: ACO2 was added to Fetal anomalies. Sources: Expert Review Amber,Genomics England PanelApp
Mode of inheritance for gene: ACO2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ACO2 were set to INFANTILE CEREBELLAR-RETINAL DEGENERATION
Fetal anomalies v0.0 WDR62 Zornitza Stark gene: WDR62 was added
gene: WDR62 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: WDR62 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: WDR62 were set to MICROCEPHALY CORTICAL MALFORMATIONS AND MENTAL RETARDATION
Fetal anomalies v0.0 VLDLR Zornitza Stark gene: VLDLR was added
gene: VLDLR was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: VLDLR was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VLDLR were set to CEREBELLAR ATAXIA MENTAL RETARDATION AND DYSEQUILIBRIUM SYNDROME TYPE 1
Fetal anomalies v0.0 UBE3B Zornitza Stark gene: UBE3B was added
gene: UBE3B was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: UBE3B was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: UBE3B were set to BLEPHAROPHIMOSIS-MENTAL RETARDATION
Fetal anomalies v0.0 TUBGCP6 Zornitza Stark gene: TUBGCP6 was added
gene: TUBGCP6 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: TUBGCP6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TUBGCP6 were set to MICROCEPHALY AND CHORIORETINOPATHY WITH OR WITHOUT MENTAL RETARDATION
Fetal anomalies v0.0 TTC8 Zornitza Stark gene: TTC8 was added
gene: TTC8 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: TTC8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TTC8 were set to RETINITIS PIGMENTOSA TYPE 51; BARDET-BIEDL SYNDROME TYPE 8
Fetal anomalies v0.0 TRAPPC9 Zornitza Stark gene: TRAPPC9 was added
gene: TRAPPC9 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: TRAPPC9 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TRAPPC9 were set to MENTAL RETARDATION AUTOSOMAL RECESSIVE TYPE 13
Fetal anomalies v0.0 TMCO1 Zornitza Stark gene: TMCO1 was added
gene: TMCO1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: TMCO1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TMCO1 were set to CRANIOFACIAL DYSMORPHISM, SKELETAL ANOMALIES, AND MENTAL RETARDATION SYNDROME
Fetal anomalies v0.0 TINF2 Zornitza Stark gene: TINF2 was added
gene: TINF2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: TINF2 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: TINF2 were set to EXUDATIVE RETINOPATHY WITH BONE MARROW FAILURE
Fetal anomalies v0.0 TBCE Zornitza Stark gene: TBCE was added
gene: TBCE was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: TBCE was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: TBCE were set to HYPOPARATHYROIDISM-RETARDATION-DYSMORPHISM SYNDROME; Early-Onset Progressive Encephalopathy with Distal Spinal Muscular Atrophy; KENNY-CAFFEY SYNDROME TYPE 1
Fetal anomalies v0.0 SPATA5 Zornitza Stark gene: SPATA5 was added
gene: SPATA5 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SPATA5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: SPATA5 were set to EPILEPSY, HEARING LOSS, AND MENTAL RETARDATION SYNDROME
Fetal anomalies v0.0 SOX3 Zornitza Stark gene: SOX3 was added
gene: SOX3 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SOX3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: SOX3 were set to Panhypopituitarism, X-linked, OMIM:312000; Panhypopituitarism, X-linked, MONDO:0010712; Intellectual disability, X-linked, with panhypopituitarism, MONDO:0010252; Mental retardation, X-linked, with isolated growth hormone deficiency, OMIM:300123
Fetal anomalies v0.0 SOX17 Zornitza Stark gene: SOX17 was added
gene: SOX17 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SOX17 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SOX17 were set to VESICOURETERAL REFLUX TYPE 3
Fetal anomalies v0.0 SETD5 Zornitza Stark gene: SETD5 was added
gene: SETD5 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SETD5 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SETD5 were set to MENTAL RETARDATION, AUTOSOMAL DOMINANT 23
Fetal anomalies v0.0 SETBP1 Zornitza Stark gene: SETBP1 was added
gene: SETBP1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: SETBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: SETBP1 were set to DEVELOPMENTAL AND EXPRESSIVE LANGUAGE DELAY; SCHINZEL-GIEDION MIDFACE RETRACTION SYNDROME
Fetal anomalies v0.0 RET Zornitza Stark gene: RET was added
gene: RET was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: RET was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: RET were set to RENAL AGENESIS; MULTIPLE ENDOCRINE NEOPLASIA IIB
Fetal anomalies v0.0 POMT2 Zornitza Stark gene: POMT2 was added
gene: POMT2 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: POMT2 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POMT2 were set to MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A2; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B2; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C2
Fetal anomalies v0.0 POMT1 Zornitza Stark gene: POMT1 was added
gene: POMT1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: POMT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POMT1 were set to MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C1; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B1; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A1
Fetal anomalies v0.0 POMGNT1 Zornitza Stark gene: POMGNT1 was added
gene: POMGNT1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: POMGNT1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: POMGNT1 were set to MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C3; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B3; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A3 (MDDGA3
Fetal anomalies v0.0 PLK4 Zornitza Stark gene: PLK4 was added
gene: PLK4 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PLK4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PLK4 were set to MICROCEPHALY, GROWTH FAILURE AND RETINOPATHY
Fetal anomalies v0.0 PIGV Zornitza Stark gene: PIGV was added
gene: PIGV was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PIGV was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIGV were set to HYPERPHOSPHATASIA WITH MENTAL RETARDATION
Fetal anomalies v0.0 PIGO Zornitza Stark gene: PIGO was added
gene: PIGO was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PIGO was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PIGO were set to HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 2
Fetal anomalies v0.0 PHF8 Zornitza Stark gene: PHF8 was added
gene: PHF8 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PHF8 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: PHF8 were set to MENTAL RETARDATION SYNDROMIC X-LINKED SIDERIUS TYPE
Fetal anomalies v0.0 PGAP3 Zornitza Stark gene: PGAP3 was added
gene: PGAP3 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PGAP3 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PGAP3 were set to HYPERPHOSPHATASIA WITH MENTAL RETARDATION SYNDROME 4
Fetal anomalies v0.0 PAK3 Zornitza Stark gene: PAK3 was added
gene: PAK3 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: PAK3 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: PAK3 were set to 24556213
Phenotypes for gene: PAK3 were set to AGENESIS OF THE CORPUS CALLOSUM; MENTAL RETARDATION X-LINKED TYPE 30
Fetal anomalies v0.0 OPHN1 Zornitza Stark gene: OPHN1 was added
gene: OPHN1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: OPHN1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: OPHN1 were set to Mental retardation, X-linked, with cerebellar hypoplasia and distinctive facial appearance, 300486
Fetal anomalies v0.0 NHEJ1 Zornitza Stark gene: NHEJ1 was added
gene: NHEJ1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: NHEJ1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: NHEJ1 were set to Severe combined immunodeficiency with microcephaly, growth retardation, and sensitivity to ionizing radiation 611291
Fetal anomalies v0.0 NALCN Zornitza Stark gene: NALCN was added
gene: NALCN was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: NALCN was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: NALCN were set to HYPOTONIA, INFANTILE, WITH PSYCHOMOTOR RETARDATION AND CHARACTERISTIC FACIES; CONGENITAL CONTRACTURES OF THE LIMBS AND FACE, HYPOTONIA, AND DEVELOPMENTAL DELAY; SEVERE HYPOTONIA, SPEECH IMPAIRMENT, AND COGNITIVE DELAY
Fetal anomalies v0.0 MEF2C Zornitza Stark gene: MEF2C was added
gene: MEF2C was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: MEF2C was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: MEF2C were set to MENTAL RETARDATION-STEREOTYPIC MOVEMENTS-EPILEPSY AND/OR CEREBRAL MALFORMATIONS
Fetal anomalies v0.0 LRP5 Zornitza Stark gene: LRP5 was added
gene: LRP5 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: LRP5 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LRP5 were set to HIGH BONE MASS TRAIT; ENDOSTEAL HYPEROSTOSIS WORTH TYPE; VITREORETINOPATHY EXUDATIVE TYPE 4; OSTEOPETROSIS AUTOSOMAL DOMINANT TYPE 1; OSTEOPOROSIS-PSEUDOGLIOMA SYNDROME
Fetal anomalies v0.0 LARGE1 Zornitza Stark gene: LARGE1 was added
gene: LARGE1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: LARGE1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LARGE1 were set to MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A6; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH MENTAL RETARDATION TYPE B6
Fetal anomalies v0.0 LAMA1 Zornitza Stark gene: LAMA1 was added
gene: LAMA1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: LAMA1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: LAMA1 were set to AUTOSOMAL RECESSIVE MENTAL RETARDATION; CEREBELLAR DYSPLASIA WITH CYSTS WITH OR WITHOUT RETINAL DYSTROPHY
Fetal anomalies v0.0 L1CAM Zornitza Stark gene: L1CAM was added
gene: L1CAM was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: L1CAM was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: L1CAM were set to 30712878; 28425981
Phenotypes for gene: L1CAM were set to MENTAL RETARDATION-APHASIA-SHUFFLING GAIT-ADDUCTED THUMBS SYNDROME; PARTIAL AGENESIS OF THE CORPUS CALLOSUM; HYDROCEPHALUS DUE TO STENOSIS OF THE AQUEDUCT OF SYLVIUS; SPASTIC PARAPLEGIA X-LINKED TYPE 1
Fetal anomalies v0.0 KIF7 Zornitza Stark gene: KIF7 was added
gene: KIF7 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KIF7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: KIF7 were set to AUTOSOMAL RECESSIVE MENTAL RETARDATION; ACROCALLOSAL SYNDROME
Fetal anomalies v0.0 KIF11 Zornitza Stark gene: KIF11 was added
gene: KIF11 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KIF11 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KIF11 were set to AUTOSOMAL-DOMINANT MICROCEPHALY ASSOCIATED WITH LYMPHEDEMA AND/OR CHORIORETINOPATHY
Fetal anomalies v0.0 KDM5C Zornitza Stark gene: KDM5C was added
gene: KDM5C was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KDM5C was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: KDM5C were set to MENTAL RETARDATION SYNDROMIC X-LINKED JARID1C-RELATED
Fetal anomalies v0.0 KAT6A Zornitza Stark gene: KAT6A was added
gene: KAT6A was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: KAT6A were set to MENTAL RETARDATION, AUTOSOMAL DOMINANT 32
Fetal anomalies v0.0 INPP5E Zornitza Stark gene: INPP5E was added
gene: INPP5E was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: INPP5E was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: INPP5E were set to MENTAL RETARDATION-TRUNCAL OBESITY-RETINAL DYSTROPHY-MICROPENIS; JOUBERT SYNDROME TYPE 1
Fetal anomalies v0.0 IL1RAPL1 Zornitza Stark gene: IL1RAPL1 was added
gene: IL1RAPL1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: IL1RAPL1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: IL1RAPL1 were set to MENTAL RETARDATION X-LINKED TYPE 21
Fetal anomalies v0.0 IARS Zornitza Stark gene: IARS was added
gene: IARS was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: IARS was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: IARS were set to 27426735
Phenotypes for gene: IARS were set to Growth retardation, impaired intellectual development, hypotonia, and hepatopathy, 617093
Fetal anomalies v0.0 HUWE1 Zornitza Stark gene: HUWE1 was added
gene: HUWE1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: HUWE1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: HUWE1 were set to MENTAL RETARDATION SYNDROMIC X-LINKED TURNER TYPE
Fetal anomalies v0.0 HCFC1 Zornitza Stark gene: HCFC1 was added
gene: HCFC1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: HCFC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: HCFC1 were set to COBALAMIN DISORDER; MENTAL RETARDATION, X-LINKED 3
Fetal anomalies v0.0 GRIN2B Zornitza Stark gene: GRIN2B was added
gene: GRIN2B was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: GRIN2B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GRIN2B were set to MENTAL RETARDATION, AUTOSOMAL DOMINANT 6; AUTISM; EPILEPTIC ENCEPHALOPATHY
Fetal anomalies v0.0 GNB1 Zornitza Stark gene: GNB1 was added
gene: GNB1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: GNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: GNB1 were set to Mental retardation, autosomal dominant 42 OMIM:616973; intellectual disability, autosomal dominant 42 MONDO:0014855
Fetal anomalies v0.0 FOXG1 Zornitza Stark gene: FOXG1 was added
gene: FOXG1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: FOXG1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: FOXG1 were set to 21441262; 19564653; 19578037; 27029630
Phenotypes for gene: FOXG1 were set to Rett Syndrome, congenital variant OMIM:613454; Rett syndrome, congenital variant MONDO:0013270
Fetal anomalies v0.0 FKTN Zornitza Stark gene: FKTN was added
gene: FKTN was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: FKTN was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FKTN were set to MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C4; CARDIOMYOPATHY DILATED TYPE 1X; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITHOUT MENTAL RETARDATION TYPE B4; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A4
Fetal anomalies v0.0 FKRP Zornitza Stark gene: FKRP was added
gene: FKRP was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: FKRP was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FKRP were set to MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH BRAIN AND EYE ANOMALIES TYPE A5; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY CONGENITAL WITH OR WITHOUT MENTAL RETARDATION TYPE B5; MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY LIMB-GIRDLE TYPE C5
Fetal anomalies v0.0 ELOVL4 Zornitza Stark gene: ELOVL4 was added
gene: ELOVL4 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ELOVL4 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ELOVL4 were set to ICHTHYOSIS, SPASTIC QUADRIPLEGIA, AND MENTAL RETARDATION
Fetal anomalies v0.0 DYRK1A Zornitza Stark gene: DYRK1A was added
gene: DYRK1A was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: DYRK1A was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: DYRK1A were set to MENTAL RETARDATION AUTOSOMAL DOMINANT TYPE 7
Fetal anomalies v0.0 DDX3X Zornitza Stark gene: DDX3X was added
gene: DDX3X was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: DDX3X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Publications for gene: DDX3X were set to 30266093; 26235985; 25533962
Phenotypes for gene: DDX3X were set to Intellectual disability; INTELLECTUAL DIABILITY; Mental retardation, X-linked 102, 300958
Fetal anomalies v0.0 CWC27 Zornitza Stark gene: CWC27 was added
gene: CWC27 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: CWC27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: CWC27 were set to 28285769
Phenotypes for gene: CWC27 were set to Retinitis pigmentosa, skeletal anomalies and intellectual disability
Fetal anomalies v0.0 CUL4B Zornitza Stark gene: CUL4B was added
gene: CUL4B was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: CUL4B was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: CUL4B were set to MENTAL RETARDATION SYNDROMIC X-LINKED CABEZAS TYPE
Fetal anomalies v0.0 CTNNB1 Zornitza Stark gene: CTNNB1 was added
gene: CTNNB1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: CTNNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications for gene: CTNNB1 were set to 27915094
Phenotypes for gene: CTNNB1 were set to MENTAL RETARDATION, AUTOSOMAL DOMINANT 19
Fetal anomalies v0.0 CTC1 Zornitza Stark gene: CTC1 was added
gene: CTC1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: CTC1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CTC1 were set to CEREBRORETINAL MICROANGIOPATHY WITH CALCIFICATIONS AND CYSTS
Fetal anomalies v0.0 COL2A1 Zornitza Stark gene: COL2A1 was added
gene: COL2A1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: COL2A1 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: COL2A1 were set to KNIEST DYSPLASIA; SPONDYLOEPIMETAPHYSEAL DYSPLASIA STRUDWICK TYPE; PLATYSPONDYLIC LETHAL SKELETAL DYSPLASIA TORRANCE TYPE; STICKLER SYNDROME TYPE 1 NON-SYNDROMIC OCULAR; RHEGMATOGENOUS RETINAL DETACHMENT AUTOSOMAL DOMINANT; SPONDYLOEPIPHYSEAL DYSPLASIA CONGENITA; ACHONDROGENESIS TYPE 2; SPONDYLOPERIPHERAL DYSPLASIA
Fetal anomalies v0.0 CKAP2L Zornitza Stark gene: CKAP2L was added
gene: CKAP2L was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: CKAP2L was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CKAP2L were set to FILIPPI SYNDROME. SYNDACTYLY, TYPE I, WITH MICROCEPHALY AND MENTAL RETARDATION
Fetal anomalies v0.0 CASK Zornitza Stark gene: CASK was added
gene: CASK was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: CASK was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes for gene: CASK were set to MENTAL RETARDATION X-LINKED CASK-RELATED; MRX WITH/WITHOUT NYSTAGMUS; FG SYNDROME TYPE 4
Fetal anomalies v0.0 CA8 Zornitza Stark gene: CA8 was added
gene: CA8 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: CA8 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: CA8 were set to CEREBELLAR ATAXIA MENTAL RETARDATION AND DYSEQUILIBRIUM SYNDROME TYPE 3
Fetal anomalies v0.0 ATRX Zornitza Stark gene: ATRX was added
gene: ATRX was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
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 X-LINKED NON-DELETION TYPE; MENTAL RETARDATION SYNDROMIC X-LINKED WITH HYPOTONIC FACIES SYNDROME TYPE 1
Fetal anomalies v0.0 ARX Zornitza Stark gene: ARX was added
gene: ARX was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ARX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Phenotypes for gene: ARX were set to AGENESIS OF THE CORPUS CALLOSUM WITH ABNORMAL GENITALIA; EPILEPTIC ENCEPHALOPATHY EARLY INFANTILE TYPE 1; PARTINGTON SYNDROME; MENTAL RETARDATION X-LINKED ARX-RELATED; LISSENCEPHALY X-LINKED TYPE 2
Fetal anomalies v0.0 ARL6 Zornitza Stark gene: ARL6 was added
gene: ARL6 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ARL6 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: ARL6 were set to RETINITIS PIGMENTOSA TYPE 55; BARDET-BIEDL SYNDROME TYPE 3
Fetal anomalies v0.0 ARID1B Zornitza Stark gene: ARID1B was added
gene: ARID1B was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ARID1B was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ARID1B were set to COFFIN SIRIS SYNDROME; MENTAL RETARDATION, AUTOSOMAL DOMINANT 12
Fetal anomalies v0.0 ALDH18A1 Zornitza Stark gene: ALDH18A1 was added
gene: ALDH18A1 was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ALDH18A1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: ALDH18A1 were set to SPASTIC PARAPLEGIA 9, AUTOSOMAL DOMINANT; MENTAL RETARDATION-JOINT HYPERMOBILITY-SKIN LAXITY WITH OR WITHOUT METABOLIC ABNORMALITIES; CUTIS LAXA, AUTOSOMAL DOMINANT 3
Fetal anomalies v0.0 ADNP Zornitza Stark gene: ADNP was added
gene: ADNP was added to Fetal anomalies. Sources: Expert Review Green,Genomics England PanelApp
Mode of inheritance for gene: ADNP was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: ADNP were set to MENTAL RETARDATION, AUTOSOMAL DOMINANT, 28