Clinical analysis of CHD2 gene mutations in pediatric patients with epilepsy

Importance CHD2 is a member of the chromodomain helicase DNA-binding (CHD) family of proteins, which have important roles in the regulation of gene expression. Dysregulation of this protein may lead to various disorders. Objective To delineate the genotypes and phenotypes of CHD2-related epilepsy. Methods We analyzed the medical history, magnetic resonance imaging findings, and video-electroencephalogram recordings of 17 patients with CHD2 mutations in the Neurology Department of Beijing Children's Hospital from June 2016 to June 2021. Results Age at seizure onset ranged from 6 months to 10 years; the median age at onset was 4 years. Generalized tonic-clonic, myoclonic, eyelid myoclonic, atonic, atypical absence, myoclonic-atonic, and spasm seizures were observed. Ten of the 17 patients had multiple types of seizures. One patient exhibited photosensitivity epilepsy and one patient exhibited grid image-induced visual reflex epilepsy. Developmental disability was present in 14 patients, while autism features were present in five patients. Sixteen patients had de novo mutations of CHD2; one patient had an inherited variant. Eleven mutations were novel. One patient had two mutations; that patient exhibited development delay and refractory epilepsy. Seizures were controlled in eight patients, improved in seven patients, and resistant to treatment in two patients. Interpretation Phenotype severity in patients with CHD2 variants ranged from drug-responsive seizures to severe epileptic encephalopathy. Most patients exhibited developmental disorders.