Cerebral vascular malformations
Gene: CHD4
Although there are four unrelated cases presenting with either cleft palate and/or bifid uvula, this phenotype is not consistent among patients identified with monoallelic variants in CHD4 gene. Hence, this gene should be added to the Clefting disorders panel with amber rating.
PMID:31388190 reported 32 patients with heterozygous variants in CHD4 gene, of which one patient (p.Gln715Ter) had cleft palate and pierre robin. In addition, another patient identified with heterozygous variant p.Arg1127Gln was reported with bifid uvula.
In addition, 2 out of 10 patients with pathogenic/ likely pathogenic heterozygous variants from the DDD study were reported with cleft palate in addition to several other clinical presentations including global developmental delay (PMID:37010288).Created: 14 Jun 2023, 6:23 p.m. | Last Modified: 15 Jun 2023, 7:16 p.m.
Panel Version: 1.941
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Sifrim-Hitz-Weiss syndrome, OMIM:617159
Publications
New publication, PMID 34109749: 8 individuals from 4 families with childhood idiopathic epilepsy and sinus arrhythmia. This may be a distinct gene-disease association as the variants were located outside of the typical domains associated with SHW syndrome (central regions from SNF2-like region to DUF1087 domain).Created: 5 Oct 2021, 7:12 a.m. | Last Modified: 5 Oct 2021, 7:12 a.m.
Panel Version: 0.9322
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Childhood idiopathic epilepsy and sinus arrhythmia
Publications
5 individuals reported with Moya Moya and ID, but only in one was de novo inheritance confirmed. 4 missense variants and one canonical splice.
Sources: LiteratureCreated: 27 Nov 2020, 2:31 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Moya Moya; intellectual disability
Publications
Many P/LP variants reported.
Missense variants disrupt ATPase activity and decrease nucleosome remodelling ability.
~50% of missense variants occur between p.1127-1192 containing motifs V, Vb and VI.Created: 20 Apr 2020, 5:08 a.m. | Last Modified: 20 Apr 2020, 5:08 a.m.
Panel Version: 0.2406
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Sifrim-Hitz-Weiss syndrome, MIM 617159
Publications
Variants in this GENE are reported as part of current diagnostic practice
Gene: chd4 has been classified as Amber List (Moderate Evidence).
Gene: chd4 has been classified as Red List (Low Evidence).
Phenotypes for gene: CHD4 were changed from Moya Moya; intellectual disability to Moya Moya; Sifrim-Hitz-Weiss syndrome, MIM# 617159
gene: CHD4 was added gene: CHD4 was added to Cerebral vascular malformations. Sources: Literature Mode of inheritance for gene: CHD4 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted Publications for gene: CHD4 were set to 31474762 Phenotypes for gene: CHD4 were set to Moya Moya; intellectual disability Penetrance for gene: CHD4 were set to Incomplete Review for gene: CHD4 was set to RED