Early onset or syndromic epilepsy

Gene: CHD4

Green List (high evidence)

The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, 11:59 a.m. | Last Modified: 11 Oct 2023, 11:59 a.m.

Panel Version: 4.110

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Green List (high evidence)

Liu et al. (2021) performed trio-WES in a childhood idiopathic epilepsy cohort and identify novel missense variants in unrelated families with epilepsy with sinus arrhythmia. In 2 families, they identified de novo variants in 1 affected individual, and in the other 2 families, they identified inherited variants that co-segregated with epilepsy in 3 affected individuals in each family. All the probands had childhood idiopathic epilepsy characterised by shifting or bilateral focal discharges, or generalised spike-slow waves with normal backgrounds of EEGs. Sinus arrhythmia was present in 7/8 individuals. No in vitro functional studies were performed on the variants. The identified variants are located outside of the typical domains associated with SHW syndrome (central regions from SNF2-like region to DUF1087 domain), representing a new phenotype for CHD4 variants. The CHD4 gene was evaluated for its association with epilepsy using the ClinGen Clinical Validity Framework by this group, and a strong association was established. In summary, this gene should be promoted to GREEN in this panel, with autosomal dominant mode of inheritance.

Created: 20 Jan 2023, 11:16 a.m. | Last Modified: 20 Jan 2023, 11:16 a.m.

Panel Version: 3.21

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Sifrim-Hitz-Weiss syndrome, OMIM:617159

Publications

• 34109749

Green List (high evidence)

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).

SHW syndrome: seizures are also reported, though not as a common feature.
Sources: Literature

Created: 11 Oct 2021, 9:49 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Sifrim-Hitz-Weiss syndrome, MIM# 617159; Childhood idiopathic epilepsy and sinus arrhythmia

Publications

• 27479907
• 27616479
• 34109749