CHD3related

CHD3-related refers to a spectrum of neurodevelopmental disorders caused by pathogenic variants in the CHD3 gene. CHD3 encodes chromodomain-helicase-DNA-binding protein 3, an ATP-dependent chromatin remodeling factor that is a component of the NuRD (nucleosome remodeling and deacetylase) complex. Through remodeling of chromatin structure, CHD3 helps regulate gene expression during development, particularly in the nervous system.

Most CHD3-related cases arise from de novo heterozygous variants, though rare familial cases due to parental mosaicism have been described. Variants can include missense, nonsense, frameshift, and splice-site changes, often leading to haploinsufficiency or altered protein function. The condition is typically inherited in an autosomal dominant manner, with wide interindividual variability in presentation.

Clinical features commonly observed in CHD3-related disorders include developmental delay and intellectual disability, difficulties with speech and language, and features of autism spectrum disorder. Hypotonia in infancy, motor coordination challenges, and feeding difficulties may be present. Growth and head circumference show variable patterns, and some individuals may have additional congenital or behavioral differences. Seizures occur in a subset of individuals, but many are not epileptic.

Diagnosis is established by genetic testing, usually with exome or targeted sequencing that identifies a pathogenic CHD3 variant. Confirmation relies on molecular evidence and careful genotype–phenotype correlation. Management is multidisciplinary and tailored to the individual, emphasizing early intervention, speech and language therapy, developmental therapies, educational supports, and seizure management if needed. Regular follow-up with neurology, genetics, and developmental specialists is common.

Research continues to clarify the full phenotypic spectrum, natural history, and underlying mechanisms of CHD3-related disorders, with emphasis on how CHD3 disruptions affect NuRD function and neurodevelopment.