CHD5 encodes for the chromodomain-helicase-DNA-binding protein 5, an ATP-dependent chromatin remodelling complex subunit of the Nucleosome Remodelling and Deacetylase (NuRD) complex. CHD5 is mainly expressed in brain and testis. In the brain, it regulates neuronal differentiation, radial migration and neuronal cell identity.
Main clinical features
Variants in CHD5 lead to a variable neurodevelopmental disorder mainly characterized by speech and motor delay, intellectual disability, behavioral disturbances, epilepsy, and hypotonia. The number and severity of the reported clinical features vary among patients.
Prevalence
CHD5-neurodevelopmental disorders are rare. So far, likely pathogenic CHD5 variants have been described in less than 20 patients. Hence, it is not yet possible to estimate the prevalence of this disorder.
Inheritance
CHD5-related disorders follow autosomal dominant inheritance. Mutations causing severe sporadic disorders mostly occur de novo. The few reported familial cases suggest the existence of intra-familial phenotypic variability and incomplete penetrance.