Cerebral vascular malformations

Gene: CHD4

Amber List (moderate evidence)

CHD4 (chromodomain helicase DNA binding protein 4)
EnsemblGeneIds (GRCh38): ENSG00000111642
EnsemblGeneIds (GRCh37): ENSG00000111642
OMIM: 603277, Gene2Phenotype
CHD4 is in 12 panels

4 reviews

Achchuthan Shanmugasundram (Genomics England)

I don't know

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

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Green List (high evidence)

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

Sue White (Victorian Clinical Genetics Services)

Red List (low evidence)

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: Literature
Created: 27 Nov 2020, 2:31 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Moya Moya; intellectual disability

Publications

Teresa Zhao (Victorian Clinical Genetics Services)

Green List (high evidence)

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

Details

Mode of Inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Sources
  • Expert Review Amber
  • Expert Review Green
  • Victorian Clinical Genetics Services
Phenotypes
  • Moya Moya
  • Sifrim-Hitz-Weiss syndrome, MIM# 617159
OMIM
603277
Clinvar variants
Variants in CHD4
Penetrance
Incomplete
Publications
Panels with this gene

History Filter Activity

20 Sep 2021, Gel status: 2

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: chd4 has been classified as Amber List (Moderate Evidence).

27 Nov 2020, Gel status: 1

Entity classified by Genomics England curator

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Gene: chd4 has been classified as Red List (Low Evidence).

27 Nov 2020, Gel status: 1

Set Phenotypes

Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)

Phenotypes for gene: CHD4 were changed from Moya Moya; intellectual disability to Moya Moya; Sifrim-Hitz-Weiss syndrome, MIM# 617159

27 Nov 2020, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes, Set penetrance

Sue White (Victorian Clinical Genetics Services)

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