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| Cerebral Palsy v1.348 | PIK3R2 |
Clare van Eyk gene: PIK3R2 was added gene: PIK3R2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PIK3R2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PIK3R2 were set to PMID: 38553553 Phenotypes for gene: PIK3R2 were set to Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1, MIM#603387 Mode of pathogenicity for gene: PIK3R2 was set to Other Review for gene: PIK3R2 was set to AMBER Added comment: Single individual with de novo heterozygous p.G373R variant described in WGS study of clinically confirmed CP (PMID: 38553553). This variant is reported multiple times in ClinVar and literature as a recurrent pathogenic activating mutation. Additional case in literature with same variant and spastic hemiplegia (PMID: 26860062). Constitutional and mosaic mutations in PIK3R2 are associated with a range of developmental brain disorders. Sources: Literature |
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| Cerebral Palsy v1.348 | PHKA2 |
Clare van Eyk gene: PHKA2 was added gene: PHKA2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PHKA2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: PHKA2 were set to PMID: 38553553 Phenotypes for gene: PHKA2 were set to Glycogen storage disease, type IXa, 306000 Review for gene: PHKA2 was set to RED Added comment: Single individual with de novo hemizygous variant described in WGS study of clinically confirmed CP (PMID: 38553553). Variant has multiple entries in ClinVar - pathogenic/likely pathogenic. GSD9A is primarily associated with liver dysfunction, however dysregulation of glucose metabolism can cause damage to the CNS. Sources: Literature |
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| Cerebral Palsy v1.343 | MUT | Zornitza Stark Marked gene: MUT as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.343 | MUT | Zornitza Stark Gene: mut has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.343 | MUT | Zornitza Stark Classified gene: MUT as Red List (low evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.343 | MUT | Zornitza Stark Gene: mut has been classified as Red List (Low Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.315 | ZDHHC9 |
Clare van Eyk gene: ZDHHC9 was added gene: ZDHHC9 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ZDHHC9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: ZDHHC9 were set to PMID: 33528536; PMID: 38693247 Phenotypes for gene: ZDHHC9 were set to Intellectual developmental disorder, X-linked syndromic, Raymond type, MIM#300799 Review for gene: ZDHHC9 was set to AMBER Added comment: Single males hemizygous for P/LP variants reported in each of 2 large CP sequencing studies (PMID: 33528536; PMID: 38693247). Detailed clinical information not supplied for either. Genome-wide significant burden of rare variants in ZDHHC9 reported in panel resequencing study of CP cohort (PMID: 31700678). Sources: Literature |
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| Cerebral Palsy v1.315 | THOC2 |
Clare van Eyk gene: THOC2 was added gene: THOC2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: THOC2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: THOC2 were set to PMID: 38168508; PMID: 38693247; PMID: 32116545 Phenotypes for gene: THOC2 were set to Intellectual developmental disorder, X-linked 12, MIM#300957 Review for gene: THOC2 was set to GREEN Added comment: 3 hemizygous males with pathogenic/likely pathogenic variants reported in large-scale CP exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Additional female with cryptogenic spastic quadriplegic CP also reported with heterozygous de novo pathogenic THOC2 variant (PMID: 38168508). Some females reported in literature previously. Dyskinesia, dystonia and spasticity are reported as clinical features in several additional cases in a series (PMID: 32116545). Sources: Literature |
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| Cerebral Palsy v1.315 | TAF1 | Clare van Eyk reviewed gene: TAF1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, X-linked syndromic 33, OMIM #300966, Dystonia-Parkinsonism, X-linked, OMIM #314250; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.315 | PQBP1 |
Clare van Eyk gene: PQBP1 was added gene: PQBP1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PQBP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: PQBP1 were set to PMID: 38693247 Phenotypes for gene: PQBP1 were set to Renpenning syndrome, MIM#309500 Review for gene: PQBP1 was set to RED Added comment: 1 hemizygous male reported with splice variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Spastic diplegia is a common feature in individuals with Renpenning syndrome. Sources: Literature |
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| Cerebral Palsy v1.315 | POLA1 |
Clare van Eyk gene: POLA1 was added gene: POLA1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: POLA1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: POLA1 were set to PMID: 38693247 Phenotypes for gene: POLA1 were set to Van Esch-O'Driscoll syndrome, MIM#301030 Review for gene: POLA1 was set to AMBER Added comment: 3 males with hemizygous LOF variants reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Spasticity has been reported as a rare feature of VEODS. Sources: Literature |
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| Cerebral Palsy v1.315 | PHF6 |
Clare van Eyk gene: PHF6 was added gene: PHF6 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PHF6 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: PHF6 were set to PMID: 38693247 Phenotypes for gene: PHF6 were set to Borjeson-Forssman-Lehmann syndrome, MIM#301900 Review for gene: PHF6 was set to RED Added comment: Single male proband with hemizygous variant impacting splicing of the first non-coding exon reported in large-scale exome sequencing study (PMID: 38693247). In silico prediction is strong, but functional impact not assessed. Detailed clinical information not supplied. BFLS is characterized by short stature, obesity, hypogonadism, hypotonia, intellectual disability, distinctive facial features, fleshy ears, and finger and toe abnormalities. Sources: Literature |
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| Cerebral Palsy v1.315 | PLP1 | Clare van Eyk reviewed gene: PLP1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Pelizaeus-Merzbacher disease MIM#312080, Spastic paraplegia 2, X-linked MIM#312920; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.315 | PIGA | Clare van Eyk reviewed gene: PIGA: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868, Neurodevelopmental disorder with epilepsy and hemochromatosis MIM#301072, Paroxysmal nocturnal hemoglobinuria, somatic MIM#300818; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.315 | OPHN1 |
Clare van Eyk gene: OPHN1 was added gene: OPHN1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: OPHN1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: OPHN1 were set to PMID: 38693247 Phenotypes for gene: OPHN1 were set to Intellectual developmental disorder, X-linked syndromic, Billuart type, MIM#300486 Review for gene: OPHN1 was set to RED Added comment: 1 male with hemizygous variant reported in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MRXSBL is associated with generalized hypotonia and delayed psychomotor development from infancy, with some individuals developing ataxia associated with cerebellar hypoplasia. Sources: Literature |
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| Cerebral Palsy v1.315 | MED12 | Clare van Eyk reviewed gene: MED12: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID 33528536; Phenotypes: Opitz-Kaveggia syndrome, MIM#305450; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.315 | MED12 |
Clare van Eyk gene: MED12 was added gene: MED12 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MED12 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: MED12 were set to PMID: 38693247 Phenotypes for gene: MED12 were set to Opitz-Kaveggia syndrome, MIM#305450 Review for gene: MED12 was set to RED Added comment: 3 individuals reported with hemizygous variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Two variants lack in silico support for pathogenicity. Sources: Literature |
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| Cerebral Palsy v1.315 | L1CAM | Clare van Eyk reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID 33528536; Phenotypes: CRASH syndrome, MIM# 303350; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.315 | KDM5C | Clare van Eyk reviewed gene: KDM5C: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534, MONDO:0010355; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.315 | HPRT1 | Clare van Eyk reviewed gene: HPRT1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Hyperuricemia, HRPT-related MIM#300323, Lesch-Nyhan syndrome MIM#300322; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.315 | HCFC1 |
Clare van Eyk gene: HCFC1 was added gene: HCFC1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: HCFC1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: HCFC1 were set to PMID: 38693247 Phenotypes for gene: HCFC1 were set to Methylmalonic aciduria and homocysteinemia, cblX type, MIM#309541 Review for gene: HCFC1 was set to AMBER Added comment: 2 males reported with hemizygous LOF variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MAHCX is characterized by severely delayed psychomotor development apparent in infancy. Sources: Literature |
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| Cerebral Palsy v1.315 | CCDC22 |
Clare van Eyk changed review comment from: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in RTSC2 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals. Sources: Literature; to: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in CCDC22 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals. Sources: Literature |
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| Cerebral Palsy v1.315 | FGD1 |
Clare van Eyk gene: FGD1 was added gene: FGD1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: FGD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: FGD1 were set to PMID: 38693247; PMID:33528536 Phenotypes for gene: FGD1 were set to Aarskog-Scott syndrome; Intellectual developmental disorder, X-linked syndromic 16, MIM#305400 Review for gene: FGD1 was set to RED Added comment: 1 individual reported with hemizygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Additional male with de novo hemizygous pathogenic variant reported in a clinical laboratory referral cohort (PMID:33528536). No clear phenotypic overlap with CP. Sources: Literature |
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| Cerebral Palsy v1.315 | EBP |
Clare van Eyk gene: EBP was added gene: EBP was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: EBP was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: EBP were set to PMID: 38693247 Phenotypes for gene: EBP were set to MEND syndrome, MIM#300960 Review for gene: EBP was set to RED Added comment: 1 individual reported with hemizygous likely pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. MEND syndrome is associated with severe neurological involvement (e.g. intellectual disability, delayed psychomotor development, seizures, hydrocephalus, cerebellar/corpus callosum hypoplasia, Dandy-Walker malformation, hypotonia). Sources: Literature |
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| Cerebral Palsy v1.315 | CLCN4 | Clare van Eyk reviewed gene: CLCN4: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247, PMID: 37789889; Phenotypes: Raynaud-Claes syndrome MIM#300114; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.315 | CCDC22 |
Clare van Eyk gene: CCDC22 was added gene: CCDC22 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: CCDC22 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: CCDC22 were set to PMID: 38693247 Phenotypes for gene: CCDC22 were set to Ritscher-Schinzel syndrome 2, MIM#300963 Review for gene: CCDC22 was set to RED Added comment: 1 individual reported with hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Mutations in RTSC2 cause syndromic ID, with hypotonia and delayed psychomotor development reported in some individuals. Sources: Literature |
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| Cerebral Palsy v1.294 | ARHGEF9 |
Clare van Eyk gene: ARHGEF9 was added gene: ARHGEF9 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ARHGEF9 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: ARHGEF9 were set to PMID: 38693247 Phenotypes for gene: ARHGEF9 were set to Developmental and epileptic encephalopathy 8, MIM#300607 Review for gene: ARHGEF9 was set to RED Added comment: 1 individual reported with hemizygous pathogenic variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Impaired psychomotor development is a feature of DEE8. Sources: Literature |
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| Cerebral Palsy v1.294 | ABCD1 |
Clare van Eyk gene: ABCD1 was added gene: ABCD1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ABCD1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: ABCD1 were set to PMID: 38693247 Phenotypes for gene: ABCD1 were set to Adrenoleukodystrophy, MIM#300100 Review for gene: ABCD1 was set to RED Added comment: 1 male with hemizygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Variable age of onset, even within same family. Heterozygous females may develop spastic paraparesis with bowel and bladder difficulties. Sources: Literature |
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| Cerebral Palsy v1.294 | SMC1A |
Clare van Eyk gene: SMC1A was added gene: SMC1A was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SMC1A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: SMC1A were set to PMID: 38693247; 26358754 Phenotypes for gene: SMC1A were set to Developmental and epileptic encephalopathy 85, with or without midline brain defects, MIM#301044 Review for gene: SMC1A was set to RED Added comment: 1 male reported with apparently hemizygous LOF variant in large-scale exome sequencing study (PMID: 38693247). LOF variants thought to be male-lethal. Detailed clinical information not supplied. 1 female in literature with a heterozygous de novo splice site mutation in SMC1A and severe encephalopathy with early-onset epilepsy who developed spastic tetraparesis (PMID: 26358754) Sources: Literature |
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| Cerebral Palsy v1.294 | SLC35A2 |
Clare van Eyk gene: SLC35A2 was added gene: SLC35A2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SLC35A2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: SLC35A2 were set to PMID: 38693247 Phenotypes for gene: SLC35A2 were set to Congenital disorder of glycosylation, type IIm, MIM#300896 Review for gene: SLC35A2 was set to RED Added comment: 1 individual reported with hemizygous stopgain variant in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Variants cause an epileptic encephalopathy which has been associated with ataxia and hypotonia. Sources: Literature |
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| Cerebral Palsy v1.294 | PDHA1 | Clare van Eyk reviewed gene: PDHA1: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Pyruvate dehydrogenase E1-alpha deficiency MIM#312170; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.294 | MECP2 | Clare van Eyk reviewed gene: MECP2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Encephalopathy, neonatal severe - 300673, Intellectual developmental disorder, X-linked syndromic, Lubs type - 300260, Intellectual developmental disorder, X-linked, syndromic 13 - 300055, Rett syndrome - 312750; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.294 | IQSEC2 | Clare van Eyk reviewed gene: IQSEC2: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder MIM#309530; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.294 | HUWE1 | Clare van Eyk reviewed gene: HUWE1: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Intellectual developmental disorder, X-linked syndromic, Turner type, MIM#309590; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.294 | CDKL5 | Clare van Eyk reviewed gene: CDKL5: Rating: AMBER; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Developmental and epileptic encephalopathy 2, MIM#300672; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.291 | POLG |
Clare van Eyk gene: POLG was added gene: POLG was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: POLG was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POLG were set to PMID: 33528536; PMID: 38693247 Phenotypes for gene: POLG were set to Mitochondrial DNA depletion syndrome 4a, MIM#203700, Mitochondrial DNA Depletion Syndrome 4B, MIM#613662, Mitochondrial recessive ataxia syndrome (includes SANDO and SCAE), MIM#607459 Review for gene: POLG was set to AMBER Added comment: 1 individual reported with biallelic P/LP missense variants in large-scale exome sequencing study (PMID: 38693247). Detailed clinical information not supplied. Additional individual reported in clinical referral cohort (PMID: 33528536). Mutations in POLG are associated with a wide range of clinical features including lactic acidosis, seizures, ataxia, peripheral neuropathy, developmental delay, myopathy, chronic progressive external ophthalmoplegia, and hepatopathy. Sources: Literature |
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| Cerebral Palsy v1.291 | MUT |
Clare van Eyk gene: MUT was added gene: MUT was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MUT was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MUT were set to PMID: 38693247 Phenotypes for gene: MUT were set to Methylmalonic aciduria, MIM#251000 Review for gene: MUT was set to AMBER Added comment: 1 individual reported with homozygous pathogenic missense variant in large-scale exome sequencing study (PMID: 38693247). Methylmalonic aciduria has a broad clinical spectrum, with neurologic manifestations, such as seizure, encephalopathy, and stroke, frequently reported. Sources: Literature |
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| Cerebral Palsy v1.194 | SPTBN2 | Clare van Eyk reviewed gene: SPTBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: PMID: 38693247; Phenotypes: Spinocerebellar ataxia 5 MIM#600224, Spinocerebellar ataxia, autosomal recessive 14 MIM#615386; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.193 | CACNA1D |
Clare van Eyk gene: CACNA1D was added gene: CACNA1D was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: CACNA1D was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CACNA1D were set to PMID: 38693247; 23913001 Phenotypes for gene: CACNA1D were set to Primary aldosteronism, seizures and neurologic abnormalities; PASNA, MIM#615474 Mode of pathogenicity for gene: CACNA1D was set to Other Review for gene: CACNA1D was set to AMBER Added comment: 1 individual with mono-allelic LP missense variant reported in large-scale exome sequencing study (PMID: 38693247). No detailed clincal data. 1 individual described previously with cerebral palsy and a de novo heterozygous gain-of-function missense mutation (PMID: 23913001). Sources: Literature |
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| Cerebral Palsy v1.187 | ESAM |
Luisa Weiss changed review comment from: Lecca et al. reported 13 individuals from 8 families (4 of which coming from the same geographical region) with a severe neurodevelopmental disorder. Although no formal diagnosis of CP was made, all patients had spasticity and most patients showed spastic tetraparesis. Many patients showed additional phenotypic features (like dysmorphism). All mutations were predicted to be Loss of function mutations. ESAM encodes an endothelial cell adhesion molecule. A recurrent variant (c.115del;p.(Arg39Glyfs∗33)) was functionally analyzed and showed to impair the in vitro tubulogenic process of endothelial colony-forming cells and to caus lack of ESAM expression in the capillary endothelial cells of damaged brain. Sources: Literature; to: Lecca et al. reported 13 individuals from 8 families (4 of which coming from the same geographical region) with a severe neurodevelopmental disorder. Although no formal diagnosis of CP was made, all patients had spasticity and most patients showed spastic tetraparesis. Many patients showed additional phenotypic features (like dysmorphism). All mutations were predicted to be Loss of function mutations. ESAM encodes an endothelial cell adhesion molecule. A recurrent variant (c.115del;p.(Arg39Glyfs∗33)) was functionally analyzed and showed to impair the in vitro tubulogenic process of endothelial colony-forming cells and to cause lack of ESAM expression in the capillary endothelial cells of damaged brain. Sources: Literature |
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| Cerebral Palsy v1.187 | ESAM |
Luisa Weiss gene: ESAM was added gene: ESAM was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ESAM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ESAM were set to 36996813 Phenotypes for gene: ESAM were set to Neurodevelopmental disorder with intracranial hemorrhage, seizures, and spasticity MIM#620371 Review for gene: ESAM was set to GREEN Added comment: Lecca et al. reported 13 individuals from 8 families (4 of which coming from the same geographical region) with a severe neurodevelopmental disorder. Although no formal diagnosis of CP was made, all patients had spasticity and most patients showed spastic tetraparesis. Many patients showed additional phenotypic features (like dysmorphism). All mutations were predicted to be Loss of function mutations. ESAM encodes an endothelial cell adhesion molecule. A recurrent variant (c.115del;p.(Arg39Glyfs∗33)) was functionally analyzed and showed to impair the in vitro tubulogenic process of endothelial colony-forming cells and to caus lack of ESAM expression in the capillary endothelial cells of damaged brain. Sources: Literature |
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| Cerebral Palsy v1.185 | SYNE1 |
Luisa Weiss edited their review of gene: SYNE1: Added comment: Two cases each in two larger CP cohort studies, one with ataxic and one with spastic CP, with biallelic SYNE1 mutations. In addition, one case report of an 18-year-old girl with CP and a heterozygous SYNE1-mutation. Not that this patient had a history of perinatal distress and asphyxia. The SYNE1 mutation was discovered at the age of 18 years due to a hypertrophic cardiomyopathy. It is uncertain whether the SYNE1 mutation is the cause for the CP.; Changed rating: GREEN; Changed publications: 34321325, 34816117, 31110749; Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal |
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| Cerebral Palsy v1.178 | AGAP1 | Clare van Eyk changed review comment from: An additional three patients with heterozygous microdeletions and phenotypic overlap with previously described patients, but none with a CP diagnosis (PMID:36778426). Overall 4/10 patients with an AGAP1 variant have CP, however not all of these were classified as pathogenic and 2/3 of the new microdeletions are inherited suggesting incomplete penetrance. Authors show that mutant Drosophila have increased lethality from exposure to environmental insult.; to: An additional three patients with heterozygous microdeletions and phenotypic overlap with previously described patients, but none with a CP diagnosis (PMID:36778426, PMID: 37470098). Overall 4/10 patients with an AGAP1 variant have CP, however not all of these were classified as pathogenic and 2/3 of the new microdeletions are inherited suggesting incomplete penetrance. Authors show that mutant Drosophila have increased lethality from exposure to environmental insult. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.146 | TSC1 |
Luisa Weiss gene: TSC1 was added gene: TSC1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: TSC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TSC1 were set to 29706646; 34788679; 25817843 Phenotypes for gene: TSC1 were set to Focal cortical dysplasia, type II, somatic MIM#607341; Lymphangioleiomyomatosis MIM#606690; Tuberous sclerosis-1 MIM#191100 Review for gene: TSC1 was set to AMBER Added comment: Two patients in large cohort studies of children with cryptogenic CP and maternally inherited mutation in TSC1, parents were mildly affected. In addition, one patient with a VUS in TSC1 with cortical and movement abnormalities, but no clinical diagnosis of TS. Sources: Literature |
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| Cerebral Palsy v1.146 | TRAPPC9 |
Luisa Weiss gene: TRAPPC9 was added gene: TRAPPC9 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: TRAPPC9 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TRAPPC9 were set to 33528536; 34540776; 36475161 Phenotypes for gene: TRAPPC9 were set to Intellectual developmental disorder, autosomal recessive MIM#13 613192 Review for gene: TRAPPC9 was set to GREEN Added comment: Two larger CP cohort studies with one patient each harboring biallelic TRAPPC9 mutations. No phenotypic information is given. In addition, one case report of a girl with CP and intellectual disability and biallelic TRAPPC9 mutations. Sources: Literature |
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| Cerebral Palsy v1.146 | TMX2 |
Luisa Weiss gene: TMX2 was added gene: TMX2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: TMX2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TMX2 were set to 31735293 Phenotypes for gene: TMX2 were set to Neurodevelopmental disorder with microcephaly, cortical malformations, and spasticity MIM#618730 Added comment: Vandervore et al. published a larger study of several patients with neurological impariment and biallelic TMX2 mutations. 8 individuals out of 5 families had previously been diagnosed with CP. Most patients had severely impaired development and epilepsy. Sources: Literature |
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| Cerebral Palsy v1.146 | TH |
Luisa Weiss gene: TH was added gene: TH was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: TH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: TH were set to 34788679 Phenotypes for gene: TH were set to Segawa syndrome, recessive MIM#605407 Review for gene: TH was set to AMBER Added comment: 2 individual cases in one large Chinese CP cohort study, both with compound heterozygous mutations. Sources: Literature |
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| Cerebral Palsy v1.146 | TEP1 |
Luisa Weiss gene: TEP1 was added gene: TEP1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: TEP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TEP1 were set to 34543729 Review for gene: TEP1 was set to GREEN Added comment: Wang et al. screened a large cohort of more than 600 CP patients from China and found several variants in TEP1, 11 of which were LoF, while no LoF variant was found in the control cohort. These children all had spastic CP. Among these 11 children, 6 children had birth asphyxia and neonatal encephalopathy. Compared to the total group with birth asphyxia (71/667), 6 patients with TEP1 LOF mutations had a significantly greater risk of birth asphyxia. They confirmed TEP1 as a risk factor for CP by cytological and animal models. Sources: Literature |
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| Cerebral Palsy v1.146 | SYNGAP1 |
Luisa Weiss gene: SYNGAP1 was added gene: SYNGAP1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SYNGAP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SYNGAP1 were set to 33528536; 31700678 Phenotypes for gene: SYNGAP1 were set to Intellectual developmental disorder, autosomal dominant 5 MIM#612621 Review for gene: SYNGAP1 was set to GREEN Added comment: Moreno de Luca et al. found 3 heterozygous de novo SYNGAP1 mutations in a large CP cohort study. In addition, van Eyk et al. found one non-maternally inherited VUS in a child with CP in a cohort study. Sources: Literature |
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| Cerebral Palsy v1.146 | SYNE1 |
Luisa Weiss gene: SYNE1 was added gene: SYNE1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SYNE1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SYNE1 were set to 34321325; 34816117 Phenotypes for gene: SYNE1 were set to Arthrogryposis multiplex congenita 3, myogenic type MIM#618484; Emery-Dreifuss muscular dystrophy 4, autosomal dominant MIM#612998; Spinocerebellar ataxia, autosomal recessive 8 MIM#610743 Review for gene: SYNE1 was set to AMBER Added comment: Two cases each in two larger CP cohort studies, one with ataxic and one with spastic CP, with biallelic SYNE1 mutations. Sources: Literature |
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| Cerebral Palsy v1.146 | SUOX |
Luisa Weiss gene: SUOX was added gene: SUOX was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SUOX was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SUOX were set to 27289259; 34540776 Phenotypes for gene: SUOX were set to Sulfite oxidase deficiency MIM#272300 Review for gene: SUOX was set to GREEN Added comment: Zaki et al. presented 3 individual cases in a larger cohort study harboring biallelic SUOX mutations and presenting with spastic quadriparesis, even though no formal CP diagnosis was given. In addition, two additional cases of patients with homozygous mutations in SUOX from a larger cohort study from Iran. Sources: Literature |
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| Cerebral Palsy v1.146 | STAMBP |
Luisa Weiss gene: STAMBP was added gene: STAMBP was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: STAMBP was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: STAMBP were set to 33528536; 23542699 Phenotypes for gene: STAMBP were set to Microcephaly-capillary malformation syndrome MIM#614261 Review for gene: STAMBP was set to GREEN Added comment: 2 cases in a larger CP cohort study with homozygous missense mutations in STAMBP, no phenotypic information is given. McDonnell et al. (23542699) presented a large cohort of previously published and unpublished patients with microcephaly-capillary malformation syndrome, which all had cutaneous abnormalities, developmental delay and epilepsy, but 8 of which presented with spastic quadriparesis. Overlap with CP is possible; however, additional phenotypic features seem to be present in any case. Sources: Literature |
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| Cerebral Palsy v1.146 | ST3GAL5 |
Luisa Weiss gene: ST3GAL5 was added gene: ST3GAL5 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ST3GAL5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ST3GAL5 were set to 34540776; 30185102; 25131622; 24026681 Phenotypes for gene: ST3GAL5 were set to Salt and pepper developmental regression syndrome MIM#609056 Review for gene: ST3GAL5 was set to GREEN Added comment: Several reports on patients with different forms of CP (dystonic, quadriplegic or spastic) later found to harbor biallelic ST3GAL5 mutations. One patient in a larger CP cohort (34540776) with a homozygous VUS, others with pathogenic mutations. Note that the patients which were presented with photographs all showed cutaneous abnormalities as well. Sources: Literature |
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| Cerebral Palsy v1.146 | SPTBN2 | Luisa Weiss reviewed gene: SPTBN2: Rating: GREEN; Mode of pathogenicity: None; Publications: 31066025, 25981959, 31721007; Phenotypes: Spinocerebellar ataxia 5 MIM#600224, Spinocerebellar ataxia, autosomal recessive 14 MIM#615386; Mode of inheritance: BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.146 | SPTBN2 |
Luisa Weiss gene: SPTBN2 was added gene: SPTBN2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SPTBN2 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: SPTBN2 were set to 31066025; 25981959; 31721007 Phenotypes for gene: SPTBN2 were set to Spinocerebellar ataxia 5 MIM#600224; Spinocerebellar ataxia, autosomal recessive 14 MIM#615386 Added comment: 5 patients presented in an overview study with ataxic CP and heterozygous (4/5) or biallelic SPTBN2 (1/5) mutations. In addition, one more case report and another case in a larger CP cohort study, all children presenting with ataxic CP. Note both heterozygous and biallelic mutations have been reported to cause ataxic CP in children, even though heterozygous mutations have previously been associated with adult onset spinocerebellar ataxia. Sources: Literature |
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| Cerebral Palsy v1.144 | SPR |
Luisa Weiss gene: SPR was added gene: SPR was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SPR was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: SPR were set to 33528536; 34540776; 22522443 Phenotypes for gene: SPR were set to Dystonia, dopa-responsive, due to sepiapterin reductase deficiency MIM#612716 Review for gene: SPR was set to GREEN Added comment: Two large CP cohort studies with one case each presenting with CP and biallelic SPR mutations. In one large study from 2012, 43 individuals with Sepiapterin reductase deficiency (SRD) were clinically analyzed, diagnoses of cerebral palsy (CP) were common, both hypotonic and dystonic. Sources: Literature |
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| Cerebral Palsy v1.144 | SPATA5 |
Luisa Weiss gene: SPATA5 was added gene: SPATA5 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SPATA5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SPATA5 were set to 33528536 Phenotypes for gene: SPATA5 were set to Neurodevelopmental disorder with hearing loss, seizures, and brain abnormalities MIM#616577 Review for gene: SPATA5 was set to GREEN Added comment: 4 individual cases in one large CP cohort study with biallelic SPATA5 mutations. Spasticity has been described in other patients as well while developmental delay seems to be mostly present. Sources: Literature |
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| Cerebral Palsy v1.144 | SLITRK2 |
Luisa Weiss gene: SLITRK2 was added gene: SLITRK2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SLITRK2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SLITRK2 were set to 35840571 Phenotypes for gene: SLITRK2 were set to Intellectual developmental disorder, X-linked MIM#301107 Review for gene: SLITRK2 was set to GREEN Added comment: Case study of several patients harboring SLITRK2 variants and neurodevelopmental delay. Three patients reported with spasticity, diplegic cerebral palsy and dystonic diplegia, respectively. Functional tests show impaired neuronal function and knock-out mice showed abnormal gait. Sources: Literature |
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| Cerebral Palsy v1.144 | SLC5A6 |
Luisa Weiss gene: SLC5A6 was added gene: SLC5A6 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SLC5A6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC5A6 were set to 33528536; 21112253; 33098801 Phenotypes for gene: SLC5A6 were set to Parkinsonism-dystonia, infantile, 1 MIM#613135 Review for gene: SLC5A6 was set to GREEN Added comment: 21112253 presents a clinical overview of 11 children with biallelic SLC6A3 mutations, 7 of which were initially diagnosed with CP. In addition, two more CP cohort studies with one patient each harboring SLC6A3 mutations. Sources: Literature |
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| Cerebral Palsy v1.144 | SLC16A2 |
Luisa Weiss gene: SLC16A2 was added gene: SLC16A2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SLC16A2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: SLC16A2 were set to 33528536; 35076175; 25280894 Phenotypes for gene: SLC16A2 were set to Allan-Herndon-Dudley syndrome MIM#300523 Review for gene: SLC16A2 was set to GREEN Added comment: Four individual cases in three large CP cohort studies presenting as dystonic or spastic CP. Mutations described were both nonsense and missense mutations and could be inherited maternally or de novo. Sources: Literature |
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| Cerebral Palsy v1.144 | SLC13A5 |
Luisa Weiss gene: SLC13A5 was added gene: SLC13A5 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SLC13A5 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SLC13A5 were set to 34364746; 34540776 Phenotypes for gene: SLC13A5 were set to Developmental and epileptic encephalopathy 25, with amelogenesis imperfecta MIM#615905 Review for gene: SLC13A5 was set to AMBER Added comment: Two large case studies with one patient described each harboring homozygous SLC13A5 variants, however, in PMID 34540776 this variant was defined as a VUS rather than a pathogenic mutation. In other described cases epilepsy and ID seem to be the main phenotypic features, while ataxia and spasticity have been desribed. Sources: Literature |
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| Cerebral Palsy v1.144 | SEPSECS |
Luisa Weiss gene: SEPSECS was added gene: SEPSECS was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SEPSECS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SEPSECS were set to 33528536; 35252561; 34540776; 36085396 Phenotypes for gene: SEPSECS were set to Pontocerebellar hypoplasia type 2D MIM#613811 Review for gene: SEPSECS was set to GREEN Added comment: Biallelic SEPSECS mutations have been described to cause Pontocerebellar hypoplasia type 2D, which usually presents with progressive microcephaly, progressive brain atrophy, ID and variable seizures and movement disorders. There have been two cases in two large CP cohort studies (33528536, 34540776) which have been proven to harbor biallelic SEPSECS variants, however, in PMID 34540776 these can only be formally classified as VUS. In addition, there is a case report (PMID 35252561) of a man presenting with no CP but spastic paraparesis and only slow disease progression in adult life (patient 48 years old at time of presentation). PMID 36085396 provides a literature review of described PCD2D patients, 72.7% of which have presented with spastic or dystonic quadriplegia, so there is significant phenotypic overlap with CP. Sources: Literature |
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| Cerebral Palsy v1.144 | SATB2 |
Luisa Weiss gene: SATB2 was added gene: SATB2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SATB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SATB2 were set to 33528536; 35076175 Phenotypes for gene: SATB2 were set to Glass syndrome MIM#612313 Review for gene: SATB2 was set to GREEN Added comment: 4 patients in 3 large CP cohort studies were found to have heterozygous de novo SATB2 mutations, three of which were nonsense and one was a missense mutation. Note that in one patient an additional acute perinatal event (neonatal compartment syndrome, intracranial hemorrhage) was present which might have added to the CP phenotype. Sources: Literature |
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| Cerebral Palsy v1.144 | SACS |
Luisa Weiss gene: SACS was added gene: SACS was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SACS was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SACS were set to 33528536; 34816117; 29997391 Phenotypes for gene: SACS were set to Spastic ataxia, Charlevoix-Saguenay type MIM#270550 Review for gene: SACS was set to GREEN Added comment: Multiple large and small cohort studies with more than 3 individual patients initially diagnosed as cerebral palsy and later diagnosed with biallelic SACS mutations. SACS is a known disease gene for spastic ataxia of Charlevoix-Saguenay, which can resemble CP but usually has a progressive course of disease. Sources: Literature |
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| Cerebral Palsy v1.144 | RARS2 |
Luisa Weiss gene: RARS2 was added gene: RARS2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: RARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RARS2 were set to 34077496; 34717047 Phenotypes for gene: RARS2 were set to Pontocerebellar hypoplasia, type 6 MIM#611523 Review for gene: RARS2 was set to GREEN Added comment: Two male patients in a large CP cohort study with either spastic quadriplegic or dyskinetic CP. Both frameshift and missense mutations have been described. PMID 34717047 presents a good overview of published cases with RARS2 mutations. Even though none of them were officially diagnosed with cerebral palsy, many showed progressive movement disorders like spastic quadriplegia, thus possibly presenting as CP. Sources: Literature |
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| Cerebral Palsy v1.144 | PTPN23 |
Luisa Weiss gene: PTPN23 was added gene: PTPN23 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PTPN23 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PTPN23 were set to 31395947; 25558065; 34064836 Phenotypes for gene: PTPN23 were set to Neurodevelopmental disorder and structural brain anomalies with or without seizures and spasticity MIM#618890 Review for gene: PTPN23 was set to AMBER Added comment: Biallelic PTPN23 mutations have been associated with neurodevelopmental delay and structural brain abnormalities in an initial study of 7 patients. In this cohort, one had the initial diagnosis of cerebral palsy (patient 6), but one other patient (patient 4) showed spasticity and contractures and thus phenotypic overlap. In addition, this study referred to another study (25558065), in which a family with PTPN23 mutations was described. Even though in PMID:31395947 this family was described as having CP, this cannot be confirmed in the initial report. Note that final exon frameshift mutations in PTPN23 have been associated complex hereditary spastic paraplegia which might hint to a phenotypic overlap to CP. Sources: Literature |
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| Cerebral Palsy v1.144 | PTPN11 |
Luisa Weiss gene: PTPN11 was added gene: PTPN11 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PTPN11 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PTPN11 were set to 33528536; 23799168 Phenotypes for gene: PTPN11 were set to LEOPARD syndrome 1 MIM#151100; Leukemia, juvenile myelomonocytic, somatic MIM#607785; Metachondromatosis MIM#156250; Noonan syndrome MIM#163950 Review for gene: PTPN11 was set to GREEN Added comment: One case report of a girl with hearing loss and CP later diagnosed as having a heterozygous de novo missense mutation in PTPN11. In addition, two individuals in a large CP cohort study with heterozygous missense PTPN11 mutations. No information about inheritance is given in these cases. Note that there is no information about additional phenotypic features in these two cases, but the girl in the case report presented with the typical clinical picture of Noonan Syndrome with multiple lentigines (NSML, formerly known as Leopard syndrome). Sources: Literature |
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| Cerebral Palsy v1.133 | PRUNE1 |
Luisa Weiss gene: PRUNE1 was added gene: PRUNE1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PRUNE1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PRUNE1 were set to 33528536; 35379233 Phenotypes for gene: PRUNE1 were set to Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies MIM#617481 Review for gene: PRUNE1 was set to GREEN Added comment: Case report of one consanguineous Iranian family with two children affected with spastic quadriplegic CP and a homozygous start loss of PRUNE1. The children also showed hypotonia and cerebellar atrophy. In addition, two additional cases in one large CP cohort study, one with homozygous mutation the other with compound heterozygous mutation/deletion. Sources: Literature |
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| Cerebral Palsy v1.133 | POMGNT1 |
Luisa Weiss gene: POMGNT1 was added gene: POMGNT1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: POMGNT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: POMGNT1 were set to 33528536; 17881266; 34077496 Phenotypes for gene: POMGNT1 were set to Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 3 MIM# 253280; Muscular dystrophy-dystroglycanopathy (congenital with impaired intellectual development), type B, 3 MIM#613151; Muscular dystrophy-dystroglycanopathy (limb-girdle), type C, 3 MIM#613157; Retinitis pigmentosa 76 MIM#617123 Review for gene: POMGNT1 was set to GREEN Added comment: One case report of two brothers diagnosed with CP and later found to have POMGnt1 biallelic mutations. In addition, two additional cases in two large CP cohort studies presenting with biallelic POMGnT1 mutations. Sources: Literature |
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| Cerebral Palsy v1.133 | POGZ |
Luisa Weiss gene: POGZ was added gene: POGZ was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: POGZ was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: POGZ were set to 33528536 Phenotypes for gene: POGZ were set to White-Sutton syndrome MIM#616364 Review for gene: POGZ was set to AMBER Added comment: 2 cases in one large cohort study, one with a likely pathogenic mutation and one with a pathogenic mutation. Sources: Literature |
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| Cerebral Palsy v1.133 | PNPLA6 |
Luisa Weiss changed review comment from: 2 case reports of patients initially reported as having CP but later re-diagnosed as having spastic paraplegia Type 39 due to biallelic PNPLA6 mutations. Significant phenotypic overlap with childhood onset of sometimes very slowly progressive motor disease Sources: Literature; to: 2 case reports of patients initially reported as having CP but later re-diagnosed as having spastic paraplegia Type 39 due to biallelic PNPLA6 mutations. Significant phenotypic overlap with HSP 39: childhood onset of potentially very slowly progressive motor disease Sources: Literature |
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| Cerebral Palsy v1.133 | PNPLA6 |
Luisa Weiss gene: PNPLA6 was added gene: PNPLA6 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PNPLA6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PNPLA6 were set to 34816117; 34364746 Phenotypes for gene: PNPLA6 were set to Boucher-Neuhauser syndrome MIM#215470; Oliver-McFarlane syndrome MIM#275400; Spastic paraplegia 39 MIM#612020 Review for gene: PNPLA6 was set to AMBER Added comment: 2 case reports of patients initially reported as having CP but later re-diagnosed as having spastic paraplegia Type 39 due to biallelic PNPLA6 mutations. Significant phenotypic overlap with childhood onset of sometimes very slowly progressive motor disease Sources: Literature |
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| Cerebral Palsy v1.88 | PMM2 |
Luisa Weiss gene: PMM2 was added gene: PMM2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PMM2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PMM2 were set to 34788679 Phenotypes for gene: PMM2 were set to Congenital disorder of glycosylation, type Ia MIM#212065 Review for gene: PMM2 was set to AMBER Added comment: One patient in a large CP cohort study was found to have biallelic mutations ins PMM2, but usually PMM2-CDG presents as a progressive multisystem disease with dysmorphism. Sources: Literature |
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| Cerebral Palsy v1.88 | PLP1 |
Luisa Weiss gene: PLP1 was added gene: PLP1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PLP1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: PLP1 were set to 33528536; 25280894; 34816117 Phenotypes for gene: PLP1 were set to Pelizaeus-Merzbacher disease MIM#312080; Spastic paraplegia 2, X-linked MIM#312920 Review for gene: PLP1 was set to GREEN Added comment: Three large cohort studies with patients initially presenting as CP found three individuals with hemizygous mutations in PLP1. Note that individuals ins PMID 33528536 and 34816117 had different base pair exchanges at the same splice site location (NM_000533:c.191+1G>T and c.191+1G>A, respectively). The other mutation was a PLP1 gene duplication. One patient also had a affected brother. Sources: Literature |
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| Cerebral Palsy v1.88 | PLA2G6 |
Luisa Weiss gene: PLA2G6 was added gene: PLA2G6 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PLA2G6 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PLA2G6 were set to 33528536; 34540776; 34788679 Phenotypes for gene: PLA2G6 were set to Infantile neuroaxonal dystrophy 1 MIM#256600; Neurodegeneration with brain iron accumulation 2B MIM#610217; Parkinson disease 14, autosomal recessive MIM#612953 Review for gene: PLA2G6 was set to GREEN Added comment: Three different individuals from three large CP cohort studies presenting with biallelic PLA2G6 mutations. Sources: Literature |
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| Cerebral Palsy v1.88 | PIGA |
Luisa Weiss gene: PIGA was added gene: PIGA was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PIGA was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: PIGA were set to 33528536; 24706016 Phenotypes for gene: PIGA were set to Multiple congenital anomalies-hypotonia-seizures syndrome 2 MIM#300868; Neurodevelopmental disorder with epilepsy and hemochromatosis MIM#301072; Paroxysmal nocturnal hemoglobinuria, somatic MIM#300818 Review for gene: PIGA was set to GREEN Added comment: One case in a large CP cohort study with maternally inherited PIGA mutation predicted to be likely pathogenic. In addition, Kato (PMID 24706016) reviewed 7 cases of boys with hemizygous PIGA mutations and encephalopathies, two of which had non-progressive hypotonic quadriplegia and one had spastic quadriplegia. They also showed intellectual disability and seizures. No CP diagnoses was given, but phenotypic overlap is present. Sources: Literature |
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| Cerebral Palsy v1.88 | PDHX |
Luisa Weiss gene: PDHX was added gene: PDHX was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PDHX was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PDHX were set to 33528536; 35076175; 34540776 Phenotypes for gene: PDHX were set to Lacticacidemia due to PDX1 deficiency MIM#245349 Review for gene: PDHX was set to GREEN Added comment: Three individual patients from three large CP cohort studies with homozygous PDHX mutations. Note that in one case (PMID 35076175) the patient had both homozygous PDHX and homozygous ACADM mutations, but his phenotype was more consistent with PDHX mutations. Sources: Literature |
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| Cerebral Palsy v1.88 | PDHA1 |
Luisa Weiss gene: PDHA1 was added gene: PDHA1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PDHA1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: PDHA1 were set to 33528536; 10486093 Phenotypes for gene: PDHA1 were set to Pyruvate dehydrogenase E1-alpha deficiency MIM#312170 Review for gene: PDHA1 was set to GREEN Added comment: 2 patients in 1 large CP cohort presented with heterozygous likely pathogenic missense mutations, one of them confirmed de novo. In an older case report (PMID:10486093) two unrelated girls were presented with cerebral palsy which were found to harbor heterozygous PDHA mutations. In one case, parental DNA wasn't analyzed, in the other case the mutation wasn't found in the healthy mother and the healthy brother of the patient. Both girls showed skewed X-Inactivation. Note that in X-linked PDH deficiency it has been shown that a high proportion of heterozygous females manifest severe symptoms. Sources: Literature |
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| Cerebral Palsy v1.88 | PAK3 | Luisa Weiss reviewed gene: PAK3: Rating: GREEN; Mode of pathogenicity: None; Publications: 31444167, 30542205, 25666757; Phenotypes: Intellectual developmental disorder, X-linked MIM#300558; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.88 | PAFAH1B1 |
Luisa Weiss gene: PAFAH1B1 was added gene: PAFAH1B1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PAFAH1B1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: PAFAH1B1 were set to 19667223 Phenotypes for gene: PAFAH1B1 were set to Lissencephaly MIM#607432; Subcortical laminar heterotopia MIM#607432 Review for gene: PAFAH1B1 was set to GREEN Added comment: Saillour reviewed 63 patients with posteriorly predominant lissencephaly, 40 of which were proven to have a LIS1 mutation. None of them were officially diagnosed with cerebral palsy, however, 24 of those 40 patients presented with "severe motor impairment including axial hypotonia and spastic quadriparesis". A high percentage of patients also showed severe developmental delay and epilepsy. Sources: Literature |
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| Cerebral Palsy v1.88 | NFIX |
Luisa Weiss gene: NFIX was added gene: NFIX was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: NFIX was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: NFIX were set to 34788679 Phenotypes for gene: NFIX were set to Malan syndrome MIM#614753; Marshall-Smith syndrome MIM#602535 Review for gene: NFIX was set to AMBER Added comment: Two patients in a large CP cohort study, one with a nonsense mutation without information on inheritance and one with a de novo missense mutation predicted to be likely pathogenic. Normally, NFIX mutation cause accelerated bone maturation with overgrwowth, dysmorphism and mental retardation, so there is a low possibility for phenotypic overlap. Sources: Literature |
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| Cerebral Palsy v1.88 | NAA10 |
Luisa Weiss gene: NAA10 was added gene: NAA10 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: NAA10 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: NAA10 were set to 33528536; 30542205 Phenotypes for gene: NAA10 were set to Microphthalmia, syndromic MIM#309800; Ogden syndrome MIM#300855 Review for gene: NAA10 was set to GREEN Added comment: Four individual cases in two large CP cohort studies. Note that in one publication (33528536) 2/3 mutations occurred de novo. Sources: Literature |
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| Cerebral Palsy v1.88 | TUBB2A |
Luisa Weiss gene: TUBB2A was added gene: TUBB2A was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: TUBB2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TUBB2A were set to 33528536; 24702957 Phenotypes for gene: TUBB2A were set to Cortical dysplasia, complex, with other brain malformations MIM# 615763 Review for gene: TUBB2A was set to GREEN Added comment: 4 individual cases in one large CP cohort study, all of them with de novo missense mutations, Note that 2/4 mutations are p.A248V, which has also been described in a nonverbal and nonambulatory girl with generalized hypotonia and mild brain malformations (dysmorphic corpus callosum). Cushion et al. (PMID 24702957) also did functional work on this variant showing is had an impaired ability to coassemble with endogenous alpha-tubulin subunits and integrate into microtubule polymers. Sources: Literature |
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| Cerebral Palsy v1.88 | TUBB3 |
Luisa Weiss gene: TUBB3 was added gene: TUBB3 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: TUBB3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: TUBB3 were set to 33528536 Phenotypes for gene: TUBB3 were set to Cortical dysplasia, complex, with other brain malformations MIM#614039; Fibrosis of extraocular muscles, congenital MIM#600638 Review for gene: TUBB3 was set to GREEN Added comment: 4 individual cases in one large CP cohort study, all with de novo missense mutations predicted to be pathogenic. Sources: Literature |
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| Cerebral Palsy v1.88 | MSL3 |
Luisa Weiss gene: MSL3 was added gene: MSL3 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MSL3 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: MSL3 were set to 33173220 Phenotypes for gene: MSL3 were set to Basilicata-Akhtar syndrome MIM#301032 Review for gene: MSL3 was set to GREEN Added comment: Brunet et al. defined the clinical phenotype of 25 patients with MSL3 mutations, three of which had initially been diagnosed as having cerebral palsy. Sources: Literature |
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| Cerebral Palsy v1.88 | MOCS2 |
Luisa Weiss gene: MOCS2 was added gene: MOCS2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MOCS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MOCS2 were set to 33528536; 22759696 Phenotypes for gene: MOCS2 were set to Molybdenum cofactor deficiency B MIM#252160 Review for gene: MOCS2 was set to GREEN Added comment: Two patients in a large CP cohort presenting with cerebral palsy. In addition one case report with a patient initially diagnosed as having CP and later found to have biallelic MOCS2 mutations. Sources: Literature |
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| Cerebral Palsy v1.88 | MEF2C |
Luisa Weiss gene: MEF2C was added gene: MEF2C was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MEF2C was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MEF2C were set to 20412115; 25817843; 33528536 Phenotypes for gene: MEF2C were set to Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language MIM#613443 Review for gene: MEF2C was set to GREEN Added comment: Two patients in two large CP cohort studies with MEF2C mutations/deletions. In addition, one case report of two patients with MEF2C mutation with one of them diagnosed as having CP. Sources: Literature |
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| Cerebral Palsy v1.88 | MOCS1 |
Luisa Weiss gene: MOCS1 was added gene: MOCS1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MOCS1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MOCS1 were set to 22759696; 34788679 Phenotypes for gene: MOCS1 were set to Molybdenum cofactor deficiency A MIM#252150 Review for gene: MOCS1 was set to AMBER Added comment: One patient described in a case report diagnosed with cerebral palsy and later re-diagnosed as having molybdenum cofactor deficiency. In addition one more patient in a large CP cohort with biallelic MOCS1 mutation. Sources: Literature |
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| Cerebral Palsy v1.88 | MAST1 |
Luisa Weiss gene: MAST1 was added gene: MAST1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MAST1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAST1 were set to 31700678; 25666757 Phenotypes for gene: MAST1 were set to Mega-corpus-callosum syndrome with cerebellar hypoplasia and cortical malformations MIM#618273 Review for gene: MAST1 was set to AMBER Added comment: Two large CP cohorts, one with one likely pathogenic de novo mutation and two VUS, one of them inherited paternally. The other cohort showed one more case with a de novo missense mutation predicted to be pathogenic. Note that no information is given on the MRI phenotype in these cohorts, so it might be a phenotypic overlap with MIM#618273. Sources: Literature |
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| Cerebral Palsy v1.88 | MLC1 |
Luisa Weiss gene: MLC1 was added gene: MLC1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MLC1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MLC1 were set to 34788679 Phenotypes for gene: MLC1 were set to Megalencephalic leukoencephalopathy with subcortical cysts MIM#604004 Review for gene: MLC1 was set to AMBER Added comment: One patient in a larger CP cohort harbouring compound heterozygous MLC1 mutations. Phenotypic overlap between MIM#604004 and CP, however, seems small, as MIM#604004 is a progressive neurological disorder with MRI abnormalities. Sources: Literature |
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| Cerebral Palsy v1.86 | WDR26 |
Luisa Weiss gene: WDR26 was added gene: WDR26 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: WDR26 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: WDR26 were set to 33528536; 34788679 Phenotypes for gene: WDR26 were set to Skraban-Deardorff syndrome MIM#617616 Review for gene: WDR26 was set to GREEN Added comment: Two large CP cohort studies with 3 individual patients harbouring de novo missense or nonsense mutations or whole gene deletions in WDR26. Sources: Literature |
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| Cerebral Palsy v1.86 | WWOX |
Luisa Weiss gene: WWOX was added gene: WWOX was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: WWOX was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: WWOX were set to 34540776; 30361190; 33528536 Phenotypes for gene: WWOX were set to Developmental and epileptic encephalopathy MIM#616211; Spinocerebellar ataxia MIM#6143223 Review for gene: WWOX was set to GREEN Added comment: 2 large CP cohort studies with 4 patients in total harbouring a biallelic WWOX mutation. In addition, case reports of patients with epileptic encephalopathy due to WWOX mutations show significant phenotypic overlap with CP Sources: Literature |
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| Cerebral Palsy v1.86 | MAP2K1 |
Luisa Weiss gene: MAP2K1 was added gene: MAP2K1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MAP2K1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MAP2K1 were set to 33528536 Phenotypes for gene: MAP2K1 were set to Cardiofaciocutaneous syndrome MIM#615279 Added comment: Four individual cases in one large CP cohort study. All of them missense and confirmed de novo. Note that the c.A389G,p.Y130C mutation affected 3/4 patients and seems to be a recurrent mutation. This mutation has also been described in patients with cardiofaciocutanuous syndrome. Sources: Literature |
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| Cerebral Palsy v1.86 | KCNT1 |
Luisa Weiss gene: KCNT1 was added gene: KCNT1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: KCNT1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNT1 were set to 33528536; 34788679 Phenotypes for gene: KCNT1 were set to Developmental and epileptic encephalopathy MIM#614959 Review for gene: KCNT1 was set to GREEN Added comment: 4 cases in two large CP cohort studies. All of them are missense mutations, mostly confirmed de novo mutations. Sources: Literature |
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| Cerebral Palsy v1.86 | KCNB1 |
Luisa Weiss gene: KCNB1 was added gene: KCNB1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: KCNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KCNB1 were set to 33528536; 34788679 Phenotypes for gene: KCNB1 were set to Developmental and epileptic encephalopathy MIM#616056 Review for gene: KCNB1 was set to AMBER Added comment: One case each in two large CP cohort studies with heterozygous missense mutations, only one of the mutations confirmed de novo. Sources: Literature |
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| Cerebral Palsy v1.86 | KAT6A |
Luisa Weiss gene: KAT6A was added gene: KAT6A was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: KAT6A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: KAT6A were set to 33528536 Phenotypes for gene: KAT6A were set to Arboleda-Tham syndrome MIM#616268 Review for gene: KAT6A was set to GREEN Added comment: Several cases in a large CP cohort study with Loss of function mutations in KAT6A, all mutations confrimed de novo Sources: Literature |
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| Cerebral Palsy v1.86 | IRF2BPL |
Luisa Weiss gene: IRF2BPL was added gene: IRF2BPL was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: IRF2BPL were set to 30057031; 30166628 Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures MIM#618088 Review for gene: IRF2BPL was set to GREEN Added comment: Two large IRF2BPL cohort studies, in one study (PMID:30166628) two children had previously been described with different forms of CP and later found to have a frameshift IRF2BPL mutation. In the other publication (PMID:3005703) there was significant phenotypic overlap with spasticity and non-progressive movemetn disorder, even though no formal CP diagnosis had been made. Sources: Literature |
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| Cerebral Palsy v1.86 | IQSEC2 | Luisa Weiss reviewed gene: IQSEC2: Rating: GREEN; Mode of pathogenicity: None; Publications: 33528536; Phenotypes: Intellectual developmental disorder MIM#09530; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.86 | IFIH1 |
Luisa Weiss gene: IFIH1 was added gene: IFIH1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: IFIH1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: IFIH1 were set to 34788679; 33177673; 33528536 Phenotypes for gene: IFIH1 were set to Aicardi-Goutieres syndrome 7 MIM#615846; Immunodeficiency 95 MIM#619773; Singleton-Merten syndrome MIM#182250 Review for gene: IFIH1 was set to GREEN Added comment: Three large CP cohort publication with one patient each presenting with CP and harbouring a IFIH1 mutation (missense mutations). Note that the gene can have a very variable phenotype and incomplete penetrance has been reported for other diseases associated with mutatons in this gene. Sources: Literature |
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| Cerebral Palsy v1.86 | HUWE1 |
Luisa Weiss gene: HUWE1 was added gene: HUWE1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: HUWE1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: HUWE1 were set to 31700678 Phenotypes for gene: HUWE1 were set to Intellectual developmental disorder, X-linked syndromic, Turner type MIM#309590 Review for gene: HUWE1 was set to AMBER Added comment: 1 large CP cohort study with three cases of HUWE1 mutation, two of which are VUS and one a likely benign variant. Note that one of the VUS is paternally inherited. No certain phenotypic overlap as HUWE1 mutations tend to cause ID, sometimes with muscular hypotonia. Sources: Literature |
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| Cerebral Palsy v1.86 | HPRT1 |
Luisa Weiss gene: HPRT1 was added gene: HPRT1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: HPRT1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: HPRT1 were set to 34788679, 30799092 Phenotypes for gene: HPRT1 were set to Hyperuricemia, HRPT-related MIM#300323; Lesch-Nyhan syndrome MIM#300322 Review for gene: HPRT1 was set to GREEN Added comment: Several (>3) cases in large CP cohort studies present with different forms of CP. Sources: Literature |
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| Cerebral Palsy v1.86 | GRIN1 |
Luisa Weiss gene: GRIN1 was added gene: GRIN1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: GRIN1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: GRIN1 were set to 33528536; 34788679 Phenotypes for gene: GRIN1 were set to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant MIM#614254 AD Review for gene: GRIN1 was set to GREEN Added comment: 3 individuals in a large CP cohort study with heterozygous mutations in GRIN1, two of which reported to be de novo. Another single patient in a large cohort study with heterozygous de novo mutation. All of these mutations are missense mutations. Note that there are other disorders associated with this gene that are due to biallelic mutations in GRIN1, however, for CP only heterozygous mutations are described so far. Sources: Literature |
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| Cerebral Palsy v1.86 | GCDH |
Luisa Weiss edited their review of gene: GCDH: Added comment: One larger cohort study on 34 patients with Glutaric Aciduria Type 1 (GA1) that showed that patient diagnosed clinically will develop a CP at school age in 64% (7 out of 11 cases). In addition, there are several case reports of patients with dystonic, dyskinetic or spastic CP that were diagnosed with biallelic mutations in GCDH and biochemically corresponding features. Also, one case in a larger cohort study of patients with atypical CP (no mutation information given for this patient).; Changed rating: GREEN; Changed publications: 30542205, 26593172, 25280894, 30271473, 35822093 |
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| Cerebral Palsy v1.86 | COL4A1 | Luisa Weiss changed review comment from: More than 8 individuals reported with heterozygous mutations in COL4A2 and CP in large cohort studies. Note that some of these mutations have been inherited from one parent so incomplete penetrance is likely. In one study, it is hypothesized that COL4A2 mutations can cause vascular instability and might thus pose a risk for perinatal intracranial hemorrhage resulting in CP.; to: More than 8 individuals reported with heterozygous mutations in COL4A1 and CP in large cohort studies. Note that some of these mutations have been inherited from one parent so incomplete penetrance is likely. In one study, it is hypothesized that COL4A1 mutations can cause vascular instability and might thus pose a risk for perinatal intracranial hemorrhage resulting in CP. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.40 | FLNA | Zornitza Stark reviewed gene: FLNA: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Heterotopia, periventricular, 1, MIM#300049; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v1.36 | GCDH |
Luisa Weiss gene: GCDH was added gene: GCDH was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: GCDH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GCDH were set to 30542205; 26593172 Phenotypes for gene: GCDH were set to Glutaricaciduria, type I MIM#231670 Review for gene: GCDH was set to AMBER Added comment: One case in a larger cohort study of patients with atypical CP, no mutation information given. One case report of one boy diagnosed with dystonic CP and homozygous missense mutation in GCDH with biochemically corresponding features. Sources: Literature |
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| Cerebral Palsy v1.36 | GABRB2 |
Luisa Weiss gene: GABRB2 was added gene: GABRB2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: GABRB2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABRB2 were set to 33528536 Phenotypes for gene: GABRB2 were set to Developmental and epileptic encephalopathy MIM#617829 Review for gene: GABRB2 was set to AMBER Added comment: Two cases in a large CP cohort study with heterozygous de novo mutations in GABRB2. Sources: Literature |
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| Cerebral Palsy v1.36 | GABRB1 |
Luisa Weiss gene: GABRB1 was added gene: GABRB1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: GABRB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: GABRB1 were set to 34540776 Phenotypes for gene: GABRB1 were set to Developmental and epileptic encephalopathy MIM#617153 Review for gene: GABRB1 was set to RED Added comment: One large cohort study on CP patients from Iran presents one patient with a heterozygous mutation in GABRB1 and atypical CP with developmental delay, ID and microcephaly. The patient's mutation (NM_000812:c.1243G>C,p.G415R) is present in a heterozygous state in the patient and no information about inheritance is given. The authors propose a recessively inherited disease. The variant is classified as a variant of unknown significance in this paper. Sources: Literature |
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| Cerebral Palsy v1.36 | FRRS1L |
Luisa Weiss gene: FRRS1L was added gene: FRRS1L was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: FRRS1L was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FRRS1L were set to 33528536; 27236917 Phenotypes for gene: FRRS1L were set to Developmental and epileptic encephalopathy MIM#616981 Review for gene: FRRS1L was set to GREEN Added comment: Three independent patients in a large CP cohort study with the same recurrent homozygous mutation (NM_014334:c.735_737del,p.245_246del). Another cohort study of multiple patients with biallelic FRRS1L mutations and epileptic-dyskinetic encephalopathy described on patient (individual 4_II-1) with non-progressive movement disorder in addition to epilepsy. Sources: Literature |
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| Cerebral Palsy v1.36 | FLNA |
Luisa Weiss gene: FLNA was added gene: FLNA was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: FLNA was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: FLNA were set to 29706646; 34077496; 25817843 Phenotypes for gene: FLNA were set to Cardiac valvular dysplasia MIM#314400; Congenital short bowel syndrome MIM#300048; Frontometaphyseal dysplasia MIM#305620; Heterotopia, periventricular MIM#300049; Intestinal pseudoobstruction MIM#300048; Melnick-Needles syndrome MIM#309350; Otopalatodigital syndrome I MIM#311300; Otopalatodigital syndrome II MIM# 304120; Terminal osseous dysplasia MIM#300244 Review for gene: FLNA was set to GREEN Added comment: In a large Chinese cohort study two male patients with hemizygous FLNA missense mutations and spastic hemiplegic CP were identified. One additional patient in a cohort study of 52 patients with CP investigated for causative CNVs. This patient harbored a pathogenic maternally inherited triplication on Xq28 including FLNA. No information about the patient's gender is given. One other cohort study (PMID 29706646) of patients with cortical malformations, which can be associated with CP overlapping features, also revealed one female patient with maternally inherited heterozygous FLNA mutation and ataxia. The mother had the same neuroradiologic features but did not show any symptoms. Sources: Literature |
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| Cerebral Palsy v1.36 | FH |
Luisa Weiss gene: FH was added gene: FH was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: FH was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FH were set to 33528536; 27541980; 1432428 Phenotypes for gene: FH were set to Fumarase deficiency MIM#606812 Review for gene: FH was set to GREEN Added comment: Two patients from a large CP cohort with biallelic (compound heterozygous) mutations in FH. Note that there is a recurrent mutation (NM_000143:c.1429_1430insAAA,p.K477delinsKK) which was already described in a compound heterozygous state in two sister with an attenuated form of fumarase deficiency and slowly progressive movement disorder (PMID:27541980). One other case report of a girl with a previous diagnosis of cerebral palsy, nonprogressive psychomotor retardation, and hypotonia and reduced fibroblast activity of FH to 10% and parental fibroblast activity of FH in the heterozygote range. No genetic testing had been performed on this patient. Sources: Literature |
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| Cerebral Palsy v1.36 | ATM |
Luisa Weiss changed review comment from: 3 individuals presenting with CP and harboring biallelic compound heterozygous mutations in ATM. At least one the individual had an overlapping phenotype of CP with Ataxia Teleangiectasia Sources: Literature; to: 3 individuals presenting with CP and harboring biallelic compound heterozygous mutations in ATM. At least one of the individual had an overlapping phenotype of CP with Ataxia Teleangiectasia Sources: Literature |
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| Cerebral Palsy v1.36 | FARS2 |
Luisa Weiss gene: FARS2 was added gene: FARS2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: FARS2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FARS2 were set to 33528536; 32989326; 25851414 Phenotypes for gene: FARS2 were set to Combined oxidative phosphorylation deficiency MIM#614946; 3 Spastic paraplegia MIM#617046 Review for gene: FARS2 was set to GREEN Added comment: Four patients out of three publications (two large CP cohort studies with one patient each, one case report of two sibling with the clinical diagnosis of CP) with biallelic mutations in FARS2. Sources: Literature |
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| Cerebral Palsy v1.36 | FAR1 |
Luisa Weiss gene: FAR1 was added gene: FAR1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: FAR1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: FAR1 were set to 33239752 Phenotypes for gene: FAR1 were set to Cataracts, spastic paraparesis, and speech delay MIM#619338 Mode of pathogenicity for gene: FAR1 was set to Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments Review for gene: FAR1 was set to GREEN Added comment: One publication with a total of 12 patients with an amino acid change at position 480 (p.Arg480Cys/His/Leu) of FAR1 and movement disorder, epilepsy and cataract. The movement disorder was non-progressive in almost all of the individuals even though the clinical diagnosis of CP was not given. Functional studies in the same publication showed that patients with the heterozygous de novo variants have elevated levels of ether lipids, including plasmalogens, which makes these mutations gain-of-function mutations (in contrast to the peroxisomal fatty acyl-CoA reductase 1 disorder, which is caused by biallelic loss-of-function mutations in the same gene). Sources: Literature |
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| Cerebral Palsy v1.36 | EEF1A2 |
Luisa Weiss gene: EEF1A2 was added gene: EEF1A2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: EEF1A2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: EEF1A2 were set to 33528536; 30109124; 32196822 Phenotypes for gene: EEF1A2 were set to Developmental and epileptic encephalopathy MIM#616409 Review for gene: EEF1A2 was set to AMBER Added comment: One patient in a large CP cohort with heterozygous EEF1A2 mutation. In another publication there is one patient from a cohort of patients with EIEE and EEF1A2 mutations that was also reported to have CP. One other paper (PMID:32196822) presents a cohort of patients with epileptic-dyskinetic encephalopathy due to heterozygous de novo EEIF1A2 mutations of which 4 had a non-progressive movement disorder without the clinical diagnosis of CP. Sources: Literature |
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| Cerebral Palsy v1.36 | ELP2 |
Luisa Weiss changed review comment from: Nine patients in two different publications described as having biallelic ELP2 mutations and a form of ID syndrome with cerebral palsy as one neurological feature. At least for one patient symptom progression was described. Sources: Literature; to: Nine patients in two different publications described as having biallelic ELP2 mutations and a form of ID syndrome with cerebral palsy as one neurological feature. For one patient symptom progression was described. Sources: Literature |
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| Cerebral Palsy v1.36 | ERCC8 |
Luisa Weiss changed review comment from: One large CP cohort study with 3 unrelated patients with biallelic mutations in ERCC8. Two were point mutations (one missense, one nonsense), the other a large deletion that included ERCC8 and NDUFAF2-gene. Another case report of a boy that was initially diagnosed as having CP but later re-diagnosed as having Cockayne syndrome due to biallelic ERCC8 mutations. Sources: Literature; to: One large CP cohort study with 3 unrelated patients with biallelic mutations in ERCC8. Two were point mutations (one missense, one nonsense), the other a large deletion that included ERCC8 and NDUFAF2-gene. Another case report of a boy that was initially diagnosed as having CP but later re-diagnosed as having Cockayne syndrome due to biallelic ERCC8 mutations because of disease progression. Sources: Literature |
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| Cerebral Palsy v1.36 | FAM126A |
Luisa Weiss gene: FAM126A was added gene: FAM126A was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: FAM126A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: FAM126A were set to 34788679 Phenotypes for gene: FAM126A were set to Leukodystrophy, hypomyelinating MIM#610532 Review for gene: FAM126A was set to AMBER Added comment: One large CP cohort study with one patient with a homozygous HYCC1/FAM126A mutation and CP Sources: Literature |
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| Cerebral Palsy v1.36 | EXOSC3 |
Luisa Weiss gene: EXOSC3 was added gene: EXOSC3 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: EXOSC3 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: EXOSC3 were set to 33528536 Phenotypes for gene: EXOSC3 were set to Pontocerebellar hypoplasia MIM#614678 Review for gene: EXOSC3 was set to GREEN Added comment: One large CP cohort study with 3 unrelated patients harboring the same homozygous missense mutation (p.D132A). The same missense mutation has been described in a homozygous state as well as compound heterozygous with a different pathogenic mutation in the same gene as causing pontocerebellar hypoplasia. Sources: Literature |
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| Cerebral Palsy v1.36 | ERCC8 |
Luisa Weiss gene: ERCC8 was added gene: ERCC8 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ERCC8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ERCC8 were set to 33528536; 30279719 Phenotypes for gene: ERCC8 were set to Cockayne syndrome MIM#216400 Review for gene: ERCC8 was set to GREEN Added comment: One large CP cohort study with 3 unrelated patients with biallelic mutations in ERCC8. Two were point mutations (one missense, one nonsense), the other a large deletion that included ERCC8 and NDUFAF2-gene. Another case report of a boy that was initially diagnosed as having CP but later re-diagnosed as having Cockayne syndrome due to biallelic ERCC8 mutations. Sources: Literature |
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| Cerebral Palsy v1.36 | ELP2 |
Luisa Weiss gene: ELP2 was added gene: ELP2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ELP2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ELP2 were set to 25131622; 33976153 Phenotypes for gene: ELP2 were set to Intellectual developmental disorder MIM#617270 Review for gene: ELP2 was set to GREEN Added comment: Nine patients in two different publications described as having biallelic ELP2 mutations and a form of ID syndrome with cerebral palsy as one neurological feature. At least for one patient symptom progression was described. Sources: Literature |
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| Cerebral Palsy v1.36 | DYRK1A |
Luisa Weiss gene: DYRK1A was added gene: DYRK1A was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: DYRK1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DYRK1A were set to 33528536 Phenotypes for gene: DYRK1A were set to Intellectual developmental disorder MIM#614104 Review for gene: DYRK1A was set to GREEN Added comment: 6 patients in one large CP cohort study described with mutations in DYRK1A. Sources: Literature |
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| Cerebral Palsy v1.36 | DYNC1H1 |
Luisa Weiss gene: DYNC1H1 was added gene: DYNC1H1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: DYNC1H1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: DYNC1H1 were set to 33528536; 25817843 Phenotypes for gene: DYNC1H1 were set to Charcot-Marie-Tooth disease MIM#614228; Cortical dysplasia, complex MIM#614563; Spinal muscular atrophy, lower extremity-predominant MIM#158600 Review for gene: DYNC1H1 was set to GREEN Added comment: Four patients with de novo heterozygous missense mutations and one patient with a de novo gene deletion in DYNC1H1 in two independent CP cohort studies described. Sources: Literature |
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| Cerebral Palsy v1.36 | CTNNA2 |
Luisa Weiss gene: CTNNA2 was added gene: CTNNA2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: CTNNA2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: CTNNA2 were set to 30013181 Phenotypes for gene: CTNNA2 were set to Cortical dysplasia, complex, with other brain malformations MIM#618174 Review for gene: CTNNA2 was set to GREEN Added comment: In 7 affected individuals of three consanguineous families a complex brain malformation syndrome with pachygyria, cortical gray matter thickening, hypogenesis of the corpus callosum, and cerebellar hypoplasia, neurodevelopmental delay, acquired microcephaly and seizures is described. All of the individuals are described as having hypotonic cerebral palsy and biallelic mutations in CTNNA2. Sources: Literature |
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| Cerebral Palsy v1.36 | CTBP1 |
Luisa Weiss gene: CTBP1 was added gene: CTBP1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: CTBP1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CTBP1 were set to 33528536 Phenotypes for gene: CTBP1 were set to Hypotonia, ataxia, developmental delay, and tooth enamel defect syndrome MIM#617915 Review for gene: CTBP1 was set to AMBER Added comment: Two independent patients in one large CP cohort studies with the same mutations in this gene (p.R342W), both heterozygous, one of them confirmed de novo. Another recurrent, possibly dominant negative functioning mutation described as causing an ID syndrome with ataxia, hypotonia and tooth enamel defects. Since there is no phenotype given in the CP cohort study, a possible phenotypic overlap cannot be ruled out. Sources: Literature |
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| Cerebral Palsy v1.36 | CREBBP |
Luisa Weiss gene: CREBBP was added gene: CREBBP was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: CREBBP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CREBBP were set to 33528536; 34788679 Phenotypes for gene: CREBBP were set to Menke-Hennekam syndrome MIM#618332, Rubinstein-Taybi syndrome MIM#180849 Review for gene: CREBBP was set to GREEN Added comment: 3 independent patients in 2 large CP cohort studies describes as having heterozygous de novo mutations in this gene. One mutation (PMID: 34788679) is a frameshift mutation, the two other mutations (PMID: 33528536) are missense mutations, one of which (p.M1872V) was already described twice in patients with Menke-Hennekam syndrome. Possible phenotypic overlap with ID syndrome. Sources: Literature |
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| Cerebral Palsy v1.36 | CLTC |
Luisa Weiss gene: CLTC was added gene: CLTC was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: CLTC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CLTC were set to 33528536; 31776469 Phenotypes for gene: CLTC were set to Intellectual developmental disorder MIM#617854 Review for gene: CLTC was set to GREEN Added comment: One large CP cohort study with one patient reported. One more publication with 13 cases of syndromic ID due to heterozygous CLTC mutations. Cerebral palsy affecting gait recurrently seen in these individuals. Sources: Literature |
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| Cerebral Palsy v1.36 | CLCN4 |
Luisa Weiss gene: CLCN4 was added gene: CLCN4 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: CLCN4 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: CLCN4 were set to 34788679 Phenotypes for gene: CLCN4 were set to Raynaud-Claes syndrome MIM#300114 Review for gene: CLCN4 was set to AMBER Added comment: One female patient presented in a large cohort study with phenotypic overlap to Raynaud-Claes syndrome (ID, epilepsy and language deficits). The mutation is a heterozygous missense mutation previously reported to cause Raynaud-Claes syndrome. Sources: Literature |
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| Cerebral Palsy v1.36 | ATP7B |
Luisa Weiss gene: ATP7B was added gene: ATP7B was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ATP7B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATP7B were set to 34788679 Phenotypes for gene: ATP7B were set to Wilson disease MIM#277900 Review for gene: ATP7B was set to RED Added comment: One reported case in a large CP cohort study with two mutations in ATP7B, however bi-parental inheritance was not confirmed. Low evidence for causality. Sources: Literature |
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| Cerebral Palsy v1.36 | CHD8 |
Luisa Weiss gene: CHD8 was added gene: CHD8 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: CHD8 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CHD8 were set to 33528536 Phenotypes for gene: CHD8 were set to Intellectual developmental disorder with autism and macrocephaly #615032 Review for gene: CHD8 was set to GREEN Added comment: 3 individual cases in one large cohort study, two de novo missense mutations and one frameshift mutation with unknown inheritance. Sources: Literature |
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| Cerebral Palsy v1.36 | CDKL5 |
Luisa Weiss gene: CDKL5 was added gene: CDKL5 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: CDKL5 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: CDKL5 were set to 33528536; 34788679 Review for gene: CDKL5 was set to AMBER Added comment: 2 individual cases in two independent large cohort studies. One mutation reported as a mosaic nonsense mutation, the other one reported as a de novo hemizygous frameshift mutation. No phenotype information given. Sources: Literature |
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| Cerebral Palsy v1.36 | CASK |
Luisa Weiss gene: CASK was added gene: CASK was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: CASK was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: CASK were set to 33528536 Phenotypes for gene: CASK were set to Intellectual developmental disorder and microcephaly with pontine and cerebellar hypoplasia MIM#300749 Review for gene: CASK was set to GREEN Added comment: 4 individual cases in one large CP cohort study. 3 of them confirmed de novo nonsense mutations, one in-frame five AA deletion with unknown inheritance. All reported to be heterozygous in an X-linked gene and thus affecting females as known for the allelic disease ID with pontine and cerebellar hypoplasia. Sources: Literature |
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| Cerebral Palsy v1.36 | BRAT1 |
Luisa Weiss gene: BRAT1 was added gene: BRAT1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: BRAT1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: BRAT1 were set to 29997391 Phenotypes for gene: BRAT1 were set to Neurodevelopmental disorder with cerebellar atrophy and with or without seizures MIM#618056; neonatal lethal rigidity and multifocal seizure syndrome MIM#614498 Review for gene: BRAT1 was set to AMBER Added comment: Biallelic BRAT1 mutations cause a neurodevelopmental phenotype with evidence of marked genotype–phenotype correlation: homozygous null variants result in a severe phenotype, whereas compound heterozygosity for null/hypomorphic variants is associated with a milder phenotype. In one study one patient with homozygous hypomorphic variants was diagnosed as a congenital cerebral palsy due to spastic paraplegia. Sources: Literature |
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| Cerebral Palsy v1.36 | ATP8A2 |
Luisa Weiss gene: ATP8A2 was added gene: ATP8A2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ATP8A2 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATP8A2 were set to 35321980; 30542205; 34077496 Phenotypes for gene: ATP8A2 were set to Cerebellar ataxia, impaired intellectual development, and dysequilibrium syndrome, MIM#615268 Review for gene: ATP8A2 was set to GREEN Added comment: 4 individuals from 3 families with biallelic mutations in ATP8A2 and CP. 3/4 patients presented with intellectual disability. PMID 35321980: Two sibling reported with a non-progressive dyskinetic cerebral palsy resembling cerebellar ataxia (athetotic movements, ptosis, ophthalmoplegia, hypotonia, delayed development) PMID 30542205: One patient with atypical CP (atypical due to intellectual disability)because intell dis and typical neurologic pattern (hypertonia, ataxia or transient episodic exacerbations of neurologic symptoms) PMID 34077496: One patient with CP and microcephaly likely due to simultaneously present biallelic CIT mutations Sources: Literature |
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| Cerebral Palsy v1.36 | ATP7A |
Luisa Weiss gene: ATP7A was added gene: ATP7A was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ATP7A was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: ATP7A were set to 35322241; 33528536; 34788679 Phenotypes for gene: ATP7A were set to Menkes disease MIM#3094009 Review for gene: ATP7A was set to GREEN Added comment: 3 individuals from 3 different publications with CP. Two patients were male with de novo splice affecting mutations. One patient was female with a heterozygous de novo frameshift mutation in ATP7B causative for the disease as described before for Menkes disease. Sources: Literature |
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| Cerebral Palsy v1.36 | ATM |
Luisa Weiss gene: ATM was added gene: ATM was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ATM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ATM were set to 34364746; 26380989; 34114234 Phenotypes for gene: ATM were set to Ataxia-telangiectasia, MIM#208900 Review for gene: ATM was set to GREEN Added comment: 3 individuals presenting with CP and harboring biallelic compound heterozygous mutations in ATM. At least one the individual had an overlapping phenotype of CP with Ataxia Teleangiectasia Sources: Literature |
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| Cerebral Palsy v1.36 | ARID2 |
Luisa Weiss gene: ARID2 was added gene: ARID2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ARID2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ARID2 were set to 33528536 Phenotypes for gene: ARID2 were set to Coffin-Siris syndrome, MIM#617808 Review for gene: ARID2 was set to GREEN Added comment: Large cohort study with three individual cases with CP and de novo ARID2 mutations (2 nonsense and 1 frameshift mutation) Sources: Literature |
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| Cerebral Palsy v1.36 | ARG1 |
Luisa Weiss gene: ARG1 was added gene: ARG1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ARG1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ARG1 were set to 35505270; 34788679 Phenotypes for gene: ARG1 were set to Argininemia MIM#207800 Review for gene: ARG1 was set to GREEN Added comment: Literature review: Three independent cases have been published with biallelic mutations in ARG1 and presenting with cerebral palsy. Two patients harbored a recurrent splice site mutation, one patient presented with compound heterozygous missense mutations. Sources: Literature |
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| Cerebral Palsy v1.36 | AKT3 |
Luisa Weiss gene: AKT3 was added gene: AKT3 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: AKT3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AKT3 were set to 34354878; 30542205; 32989326 Review for gene: AKT3 was set to AMBER Added comment: Two individual patients with CP and an AKT3 mutation have been published. In one of them (PMID 34354878) CP might be caused by birth asphyxia and is not be related to the AKT3 mutation. Additionally, there is functional data supporting the hypothesis that AKT3 might be a causative gene (PMID 32989326). PMID 34354878: One patient described as presenting with MPPH and having a mutation in AKT3, while the mutation itself is not named (unknown whether LoF or missense, de novo or inherited). CP is listed as a coexisting feature in this patient which was caused by birth asphyxia due to umbilical cord strangulation around his neck. 30542205: One additional case with atypical CP (atypical due to major brain malformations and progressive neurologic disease) and a de novo missense mutation Sources: Literature |
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| Cerebral Palsy v1.36 | AHDC1 |
Luisa Weiss gene: AHDC1 was added gene: AHDC1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: AHDC1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: AHDC1 were set to 33528536 Phenotypes for gene: AHDC1 were set to Xia-Gibbs syndrome, MIM#615829 Review for gene: AHDC1 was set to GREEN Added comment: 3 individuals in CP cohort with mono-allelic de novo variants (2 frameshift, 1 6-AA-deletion). Other ADHC1 frameshift mutations have been known to cause an early onset neurological disorder with absent or poor expressive language, obstructive sleep apnea and brain abnormalities. Sources: Literature |
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| Cerebral Palsy v1.36 | ADNP |
Luisa Weiss gene: ADNP was added gene: ADNP was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ADNP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ADNP were set to 33528536 Phenotypes for gene: ADNP were set to Helsmoortel-van der Aa syndrome MIM#615873 Review for gene: ADNP was set to AMBER Added comment: Large cohort study of cerebral palsy cases identified two variants in two individual patients with CP. One mutation was a recurrent Helsmoortel-van der Aa-syndrome nonsense mutation, the other was a de novo frameshift mutation. No further information about the patient's phenotype was given. Sources: Literature |
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| Cerebral Palsy v1.36 | ACADM |
Luisa Weiss gene: ACADM was added gene: ACADM was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ACADM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: ACADM were set to 11263545; 35076175 Phenotypes for gene: ACADM were set to Acyl-CoA dehydrogenase, medium chain, deficiency of, MIM# 201450 Review for gene: ACADM was set to AMBER Added comment: Currently unclear if variants in this gene can cause CP. If so, CP is likely to happen as a secondary effect of the brain damage happening if Acyl-CoA dehydrogenase deficiency is not treated correctly or early enough. According to one study, CP can be present in 9% of cases with biallelic mutations in ACADM, probably secondary to the underlying disease and associated with early-onset seizures (PMID 11263545). In a second publication one other case of CP associated with biallelic mutations in ACADM was presented, but this patient's phenotype was likely caused by biallelic mutations in PDHX which were present simultaneously. Sources: Literature |
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| Cerebral Palsy v1.36 | ADCY5 |
Luisa Mackenroth gene: ADCY5 was added gene: ADCY5 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ADCY5 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ADCY5 were set to 33528536; 33098801 Phenotypes for gene: ADCY5 were set to Dyskinesia with orofacial involvement MIM#606703 Mode of pathogenicity for gene: ADCY5 was set to Other Review for gene: ADCY5 was set to GREEN Added comment: Multiple individuals reported in two different cohort studies analyzing children diagnosed with CP. Clinical overlap with childhood onset dystonia likely. Reported mutations in CP patients indicate gain-of-function mechanism, but loss-of-function mechanism has been described for allelic mutations. Sources: Literature |
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| Cerebral Palsy v1.23 | ELOVL1 |
Clare van Eyk changed review comment from: Same novel heterozygous missense variant reported in 2 families (p.Ser165Phe, described twice in the literature, PMIDs 30487246 and 29496980) de novo in one family, unknown inheritance in a second) with similar phenotype which included icthyotic keratoderma, spasticity, hypomyelination and some dysmorphism. Fatty acid profile was altered in HEK293 cells transfected with mutant construct. An additional 2 members of a consanguineous family both with cerebral palsy were described with a novel homozygous variant affecting splicing of ELOVL1 and similar clinical phenotype with earlier onset and more severe phenotype (PMID 35379526) . Heterozygous parents are unaffected. Patient skin samples show defects in very long chain fatty acid synthesis. Sources: Literature; to: Same novel heterozygous missense variant reported in 2 families (p.Ser165Phe, described twice in the literature, PMIDs 30487246 and 29496980) de novo in one family, unknown inheritance in a second) with similar phenotype which included icthyotic keratoderma, spasticity, hypomyelination and some dysmorphism. Fatty acid profile was altered in HEK293 cells transfected with mutant construct. An additional 2 members of a consanguineous family both with cerebral palsy were described with a novel homozygous variant affecting splicing of ELOVL1 and similar clinical phenotype with earlier onset and more severe phenotype (PMID 35379526) . Heterozygous parents are unaffected. Patient skin samples show defects in very long chain fatty acid synthesis. Sources: Literature |
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| Cerebral Palsy v1.23 | ELOVL1 |
Clare van Eyk gene: ELOVL1 was added gene: ELOVL1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ELOVL1 was set to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal Publications for gene: ELOVL1 were set to (PMID: 35379526; 30487246; 29496980) Phenotypes for gene: ELOVL1 were set to MIM 618527 Review for gene: ELOVL1 was set to GREEN Added comment: Same novel heterozygous missense variant reported in 2 families (p.Ser165Phe, described twice in the literature, PMIDs 30487246 and 29496980) de novo in one family, unknown inheritance in a second) with similar phenotype which included icthyotic keratoderma, spasticity, hypomyelination and some dysmorphism. Fatty acid profile was altered in HEK293 cells transfected with mutant construct. An additional 2 members of a consanguineous family both with cerebral palsy were described with a novel homozygous variant affecting splicing of ELOVL1 and similar clinical phenotype with earlier onset and more severe phenotype (PMID 35379526) . Heterozygous parents are unaffected. Patient skin samples show defects in very long chain fatty acid synthesis. Sources: Literature |
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| Cerebral Palsy v1.22 | SPTAN1 |
Chirag Patel edited their review of gene: SPTAN1: Added comment: Leveille et al (2019) - 2 patients with HSP with biallelic missense SPTAN1 variants Previously described zebrafish, mouse, and rat animal models of SPTAN1 deficiency, all consistently showing axonal degeneration, fitting the pathological features of HSP in humans. Xie et al (2022) - 1 patient with complicated HSP and homozygous SPTAN1 mutation. Healthy parents and sister all carried the heterozygous mutation. Van de Vondel et al (2022) - 22 patients from 14 families with five novel heterozygous SPTAN1 variants. Presentations ranged from cerebellar ataxia, intellectual disability, epilepsy, and spastic paraplegia. A recurrent missense mutation (p.Arg19Trp) in 15 patients with spastic paraplegia. Through protein modeling they showed that mutated amino acids are located at crucial interlinking positions, interconnecting the three-helix bundle of a spectrin repeat.; Changed publications: PMID: 35150594, 34526651, 31515523; Changed phenotypes: Spastic Paraplegia |
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| Cerebral Palsy v1.21 | SCN2A |
Clare van Eyk gene: SCN2A was added gene: SCN2A was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SCN2A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SCN2A were set to 33528536; 29761117; 34114234 Phenotypes for gene: SCN2A were set to Developmental and epileptic encephalopathy 11 (DEE11), MIM# 613721 Review for gene: SCN2A was set to GREEN Added comment: Four single cases with de novo pathogenic/likely pathogenic missense variants in individuals with a clinical diagnosis of cerebral palsy. Mutations in SCN2A cause a spectrum of early-onset epileptic encephalopathies, with some cases reported to have movement disorders clinically overlapping with cerebral palsy. Sources: Literature |
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| Cerebral Palsy v1.14 | WDR45 |
Chirag Patel gene: WDR45 was added gene: WDR45 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: WDR45 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: WDR45 were set to PMID: 33528536, 34364746 Phenotypes for gene: WDR45 were set to Neurodegeneration with brain iron accumulation 5, OMIM # 300894 Review for gene: WDR45 was set to GREEN Added comment: Established gene for neurodevelopmental/degenerative disorder with spasticity and dystonia. Moreno-De-Luca et al. (2021) reported 4 patients with CP with P/LP variants. Zahrani et al. (2021) reported 2 patients with dystonic/hypotonic CP with variants. Sources: Literature |
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| Cerebral Palsy v0.180 | SAMHD1 |
Chirag Patel gene: SAMHD1 was added gene: SAMHD1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SAMHD1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SAMHD1 were set to PMID: 19525956 Phenotypes for gene: SAMHD1 were set to Aicardi-Goutieres syndrome 5; OMIM #612952 Review for gene: SAMHD1 was set to GREEN Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood. Rice et al. (2009) reported biallelic SAMHD1 mutations in 13 families with AGS. Sources: Literature |
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| Cerebral Palsy v0.178 | RNASEH2C |
Chirag Patel gene: RNASEH2C was added gene: RNASEH2C was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: RNASEH2C was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2C were set to PMID: 17846997 Phenotypes for gene: RNASEH2C were set to Aicardi-Goutieres syndrome 3; OMIM #610329 Review for gene: RNASEH2C was set to GREEN Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood. Rice et al. (2007) reported biallelic RNASEH2C mutations in 18 families with AGS. Sources: Literature |
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| Cerebral Palsy v0.176 | RNASEH2A |
Chirag Patel gene: RNASEH2A was added gene: RNASEH2A was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: RNASEH2A was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2A were set to PMID: 17846997 Phenotypes for gene: RNASEH2A were set to Aicardi-Goutieres syndrome 4; OMIM #610333 Review for gene: RNASEH2A was set to GREEN Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood. Rice et al. (2007) reported biallelic RNASEH2A mutations in 3 families with AGS. Sources: Literature |
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| Cerebral Palsy v0.175 | RNASEH2B |
Chirag Patel gene: RNASEH2B was added gene: RNASEH2B was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: RNASEH2B was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: RNASEH2B were set to PMID: 17846997, 28762473 Phenotypes for gene: RNASEH2B were set to Aicardi-Goutieres syndrome 2; OMIM #610181 Review for gene: RNASEH2B was set to GREEN Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood. Rice et al. (2007) reported biallelic RNASEH2B mutations in 47 families with AGS. Svingen et al. (2017) reported 2 siblings with atypical AGS with spastic quadriplegia, anarthria, preserved intellect, and increased iron signal in basal ganglia and homozygous RNASEH2B pathogenic variant. Sources: Literature |
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| Cerebral Palsy v0.173 | TREX1 |
Chirag Patel gene: TREX1 was added gene: TREX1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: TREX1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: TREX1 were set to PMID: 17846997, 33528536 Phenotypes for gene: TREX1 were set to Aicardi-Goutieres syndrome 1, dominant and recessive, OMIM #225750 Review for gene: TREX1 was set to GREEN Added comment: Aicardi-Goutieres syndrome is characterised by cerebral atrophy, leukodystrophy, intracranial calcifications, chronic CSF lymphocytosis, and increased CSF alpha-interferon, and neurologic dysfunction (progressive microcephaly, spasticity, dystonic posturing, profound psychomotor retardation), and often death in early childhood. Rice et al. (2007) reported biallelic TREX1 mutations in 31 families with AGS, and de novo heterozygous TREX1 mutation in 1 patient with AGS. Moreno-De-Luca et al. (2021) reported 1 patient with CP and paternally inherited pathogenic variant. Sources: Literature |
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| Cerebral Palsy v0.171 | TAF1 |
Chirag Patel gene: TAF1 was added gene: TAF1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: TAF1 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: TAF1 were set to PMID: 26637982, 33528536, 17273961 Phenotypes for gene: TAF1 were set to Intellectual developmental disorder, X-linked syndromic 33, OMIM #300966; Dystonia-Parkinsonism, X-linked, OMIM #314250 Review for gene: TAF1 was set to GREEN Added comment: O'Rawe et al. (2015) reported 12 boys from 9 unrelated families with X-linked global developmental delay, intellectual disability, dysmorphism, generalized hypotonia, microcephaly and variable neurologic features (hypoplastic CC, spastic diplegia, dystonic movements, tremors). They identified 9 different hemizygous mutations in TAF1 gene (most de novo, 3 maternally inherited). No functional studies. The mutations were found by WGS, WES, targeted panel and microarray, and all confirmed by Sanger sequencing. Moreno-De-Luca et al. (2021) reported 2 patients with CP and de novo LP variant. Note: X-linked dystonia-parkinsonism (XDP) is caused by an SVA (short interspersed nuclear element, variable number of tandem repeats, and Alu composite) retrotransposon insertion in intron 32 of TAF1, which encodes the largest component of the TFIID complex, and resulted in significantly decreased expression levels of TAF1 and the dopamine receptor D2 gene (DRD2) in the caudate nucleus. Sources: Literature |
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| Cerebral Palsy v0.168 | SPTAN1 |
Chirag Patel gene: SPTAN1 was added gene: SPTAN1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SPTAN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SPTAN1 were set to PMID: 20493457, 33528536, 34364746 Phenotypes for gene: SPTAN1 were set to Developmental and epileptic encephalopathy 5; OMIM #613477 Review for gene: SPTAN1 was set to GREEN Added comment: Developmental and epileptic encephalopathy-5 (DEE5) is a neurologic disorder characterised by tonic seizures/infantile spasms in first months of life, global developmental delay, lack of visual attention, poor head control, feeding difficulties, microcephaly, and spastic quadriplegia. Brain imaging may show cerebral atrophy and hypomyelination. Saitsu et al (2010) reported 2 patients with de novo in-frame mutations of SPTAN1 with early-onset WS with spastic quadriplegia, poor visual attention, and severe developmental delay. Moreno-De-Luca et al (2021) reported 3 patients with CP with de novo LP/P variants. Zahrani et al (2021) reported 1 patient with NDD (CP features) with de novo LP variant Sources: Literature |
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| Cerebral Palsy v0.166 | ZSWIM6 |
Chirag Patel gene: ZSWIM6 was added gene: ZSWIM6 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: ZSWIM6 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: ZSWIM6 were set to PMID: 29198722 Phenotypes for gene: ZSWIM6 were set to Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features, OMIM #617865 Review for gene: ZSWIM6 was set to GREEN Added comment: Palmer et al. (2017) reported 7 unrelated patients with neurodevelopmental disorder with movement abnormalities spasticity, abnormal gait, and autistic features. WES/WGS identified the same heterozygous R913X variant in exon 13 of ZSWIM6 gene (de novo in 6, unk in 1). The mutation was not found in gnomAD. Analysis of patient cells indicated that the mutant transcript escaped nonsense-mediated mRNA decay, and most likely produced a truncated protein, although antibody studies were unable to detect a truncated protein. Note: de novo missense variant within C-terminal Sin3-like domain of ZSWIM6 reported to cause acromelic frontonasal dysostosis (AFND), via a proposed gain-of-function effect. Sources: Literature |
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| Cerebral Palsy v0.161 | MFN2 |
Krithika Murali gene: MFN2 was added gene: MFN2 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MFN2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: MFN2 were set to 16437557; 21715711; 34114234; 33528536 Phenotypes for gene: MFN2 were set to Charcot-Marie-Tooth disease, axonal, type 2A2A - #609260; Charcot-Marie-Tooth disease, axonal, type 2A2B - #617087; Hereditary motor and sensory neuropathy VIA - 601152 Review for gene: MFN2 was set to RED Added comment: Most common cause of axonal Charcot-Marie-Tooth disease (CMT2). Homozygous and compound heterozygous MFN2 mutations have been reported in early-onset CMT2, including patients diagnosed <12 months of age. x1 het VUS reported in a prematurely born child with unilateral spastic CP (34114234) x1 paternally inherited pathogenic variant in MFN2 reported in 1 patient in CP cohort (33528536) Sources: Literature |
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| Cerebral Palsy v0.157 | MECP2 |
Krithika Murali gene: MECP2 was added gene: MECP2 was added to Cerebral Palsy. Sources: Expert list,Literature Mode of inheritance for gene: MECP2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: MECP2 were set to 30542205; 33528536 Phenotypes for gene: MECP2 were set to Encephalopathy, neonatal severe - 300673; Intellectual developmental disorder, X-linked syndromic, Lubs type - 300260; Intellectual developmental disorder, X-linked, syndromic 13 - 300055; Rett syndrome - 312750 Review for gene: MECP2 was set to GREEN Added comment: Pathogenic/likely pathogenic variants reported in 9 unrelated patients with CP Sources: Expert list, Literature |
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| Cerebral Palsy v0.148 | IQSEC2 |
Zornitza Stark gene: IQSEC2 was added gene: IQSEC2 was added to Cerebral Palsy. Sources: Expert list Mode of inheritance for gene: IQSEC2 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: IQSEC2 were set to 33368194; 20473311; 23674175 Phenotypes for gene: IQSEC2 were set to Mental retardation, X-linked 1/78, MIM# 309530, MONDO:0010656; Severe intellectual disability-progressive postnatal microcephaly- midline stereotypic hand movements syndrome MONDO:0018347 Review for gene: IQSEC2 was set to RED Added comment: More than 20 unrelated families reported. Typical features are ID, microcephaly and hand stereotypies. Phenotypic overlap with Angelman-Rett-like syndromes rather than CP. Sources: Expert list |
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| Cerebral Palsy v0.142 | ZC4H2 | Zornitza Stark Mode of inheritance for gene: ZC4H2 was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.141 | ZC4H2 | Zornitza Stark reviewed gene: ZC4H2: Rating: GREEN; Mode of pathogenicity: None; Publications: 23623388; Phenotypes: Wieacker-Wolff syndrome, MIM# 314580; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.136 | PAK3 | Zornitza Stark Mode of inheritance for gene: PAK3 was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.134 | PAK3 | Zornitza Stark reviewed gene: PAK3: Rating: RED; Mode of pathogenicity: None; Publications: 25666757; Phenotypes: Intellectual developmental disorder, X-linked 30, MIM# 300558; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.129 | SCN1A |
Clare van Eyk gene: SCN1A was added gene: SCN1A was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: SCN1A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: SCN1A were set to PMID: 33528536; PMID: 34364746; PMID: 34114234 Phenotypes for gene: SCN1A were set to Developmental and epileptic encephalopathy 6B, non-Dravet (OMIM 619317); Dravet syndrome (OMIM 607208) Review for gene: SCN1A was set to GREEN Added comment: Six cases described with missense (3 cases) or loss of function (3 cases) variants in SCN1A in individuals diagnosed with cerebral palsy. Mutations in SCN1A cause a spectrum of early-onset epileptic encephalopathies, with some cases reported to have movement disorders clinically overlapping with cerebral palsy. Sources: Literature |
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| Cerebral Palsy v0.121 | PCDH12 |
Clare van Eyk gene: PCDH12 was added gene: PCDH12 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: PCDH12 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: PCDH12 were set to PMID: 34321325; PMID: 29556033 Phenotypes for gene: PCDH12 were set to Diencephalic-mesencephalic junction dysplasia syndrome 1 (OMIM 251280) Review for gene: PCDH12 was set to GREEN Added comment: One case with homozygous nonsense variant reported with dysmorphic features, dystonic cerebral palsy and comorbidities including intellectual disability. Second individual with compound heterozygous truncating PCDH12 variants diagnosed as dyskinetic cerebral palsy with epilepsy and severe intellectual disability. Biallelic PCDH12 mutations cause a syndromic neurodevelopmental disorder with spasticity or dystonia. Sources: Literature |
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| Cerebral Palsy v0.114 | DDX3X |
Danielle Ariti gene: DDX3X was added gene: DDX3X was added to Cerebral Palsy. Sources: Expert list Mode of inheritance for gene: DDX3X was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: DDX3X were set to 33528536 Phenotypes for gene: DDX3X were set to Cerebral Palsy; Intellectual developmental disorder, X-linked, syndrome, Snijders Blok type MIM# 300958 Review for gene: DDX3X was set to GREEN Added comment: 6 individuals in CP cohort reported with de novo DDX3X variants. Sources: Expert list |
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| Cerebral Palsy v0.99 | NEXMIF |
Clare van Eyk gene: NEXMIF was added gene: NEXMIF was added to Cerebral Palsy. Sources: Expert list Mode of inheritance for gene: NEXMIF was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: NEXMIF were set to X-linked Intellectual disability; epilepsy; autism Penetrance for gene: NEXMIF were set to Incomplete Review for gene: NEXMIF was set to RED Added comment: Variants cause X-linked intellectual disability 98 (OMIM:300912). Developmental and epileptic encephalopathy with some affected individuals having movement phenotypes which could be considered CP-like, but did not find any reports in CP cohorts to date. Sources: Expert list |
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| Cerebral Palsy v0.93 | BCAP31 |
Zornitza Stark gene: BCAP31 was added gene: BCAP31 was added to Cerebral Palsy. Sources: Expert Review Mode of inheritance for gene: BCAP31 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Publications for gene: BCAP31 were set to 24011989; 31330203 Phenotypes for gene: BCAP31 were set to Deafness, dystonia, and cerebral hypomyelination, MIM# 300475 Review for gene: BCAP31 was set to GREEN Added comment: Phenotypic overlap with CP due to combination of almost no psychomotor development with dystonia and pyramidal signs. At least one patient reported who specifically had a CP diagnosis. Sources: Expert Review |
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| Cerebral Palsy v0.88 | ATRX |
Zornitza Stark gene: ATRX was added gene: ATRX was added to Cerebral Palsy. Sources: Expert Review Mode of inheritance for gene: ATRX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ATRX were set to Alpha-thalassemia/mental retardation syndrome, MIM# 301040; Mental retardation-hypotonic facies syndrome, X-linked, MIM# 309580 Review for gene: ATRX was set to GREEN Added comment: ID and hypotonia/hypertonia/spasticity: phenotypic overlap with CP. Well established gene-disease association. Sources: Expert Review |
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| Cerebral Palsy v0.83 | ARX |
Zornitza Stark gene: ARX was added gene: ARX was added to Cerebral Palsy. Sources: Expert Review Mode of inheritance for gene: ARX was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females Phenotypes for gene: ARX were set to Developmental and epileptic encephalopathy 1, MIM# 308350; Lissencephaly, X-linked 2, MIM# 300215; Proud syndrome, MIM# 300004 Review for gene: ARX was set to GREEN Added comment: Well established gene-disease association. Phenotypic overlap: ID/seizures/abnormal tone. Sources: Expert Review |
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| Cerebral Palsy v0.57 | KDM5C | Zornitza Stark Mode of inheritance for gene: KDM5C was changed from Unknown to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.56 | KDM5C | Zornitza Stark reviewed gene: KDM5C: Rating: GREEN; Mode of pathogenicity: None; Publications: 15586325, 32279304; Phenotypes: Mental retardation, X-linked, syndromic, Claes-Jensen type, MIM# 300534, MONDO:0010355; Mode of inheritance: X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.55 | MINPP1 |
Zornitza Stark gene: MINPP1 was added gene: MINPP1 was added to Cerebral Palsy. Sources: Literature Mode of inheritance for gene: MINPP1 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: MINPP1 were set to 33257696 Phenotypes for gene: MINPP1 were set to Pontocerebellar hypoplasia Review for gene: MINPP1 was set to GREEN Added comment: 8 individuals from 6 unrelated families reported with bi-allelic LOF variants. All presented with almost complete absence of motor and cognitive development, progressive or congenital microcephaly, spastic tetraplegia or dystonia, and vision impairments. For most, the first symptoms included neonatal severe axial hypotonia and epilepsy that started during the first months or years of life. Prenatal symptoms of microcephaly associated with increased thalami echogenicity were detected in one, while the seven other individuals presented with progressive microcephaly. Some exhibited rapidly progressive phenotype and the affected children died in their infancy or middle-childhood. Strikingly, all the affected children had a unique brain MRI showing a mild to severe PCH, fluid-filled posterior fossa, with dilated lateral ventricles. In addition, severe atrophy at the level of the basal ganglia or thalami often associated with typical T2 hypersignal were identified in all the patients MRI. Supportive functional data showing accumulation of highly phosphorylated inositols, mostly inositol hexakisphosphate (IP6), detected in HEK293 cells, fibroblasts, iPSCs and differentiating neurons lacking MINPP1. In mutant cells, higher IP6 level is expected to be associated with an increased chelation of intracellular cations, such as iron or calcium, resulting in decreased levels of available ions. Sources: Literature |
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| Cerebral Palsy v0.39 | L1CAM | Zornitza Stark Mode of inheritance for gene: L1CAM was changed from Unknown to X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Cerebral Palsy v0.38 | L1CAM | Zornitza Stark reviewed gene: L1CAM: Rating: GREEN; Mode of pathogenicity: None; Publications: 31700678; Phenotypes: CRASH syndrome, MIM# 303350; Mode of inheritance: X-LINKED: hemizygous mutation in males, biallelic mutations in females | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||