Abstract:

Objective To analyze the clinical features and genetic characteristics of patients with epilepsy associated with CHD2 gene variants. Methods The clinical features, electroencephalogram (EEG), genotypes and responses to the anti-seizure medications (ASM) of 6 patients with CHD2 gene variants were retrospectively analyzed. Results The onset age of seizures in the 6 patients (5 males and 1 female) ranged from 20 months to 12 years. Multiple seizure types were observed, including focal seizures in 3 cases, generalized tonic-clonic seizures in 3 cases, eyelid myoclonus with or without absence seizures in 2 cases, atypical absence seizures in 1 case, epileptic spasms in 1 case, myoclonic seizures in 1 case and tonic seizures in 1 case. Three patients were diagnosed with epilepsy syndrome, of which 2 were Jeavons syndrome and 1 was Lennox-Gastaut syndrome. Two cases were photosensitive. All 6 patients had comorbidities, including 6 patients 6 were intellectual disability, 3 attention deficit hyperactivity disorder, 2 autism spectrum disorders, and 1 mental disorder. 4 patients carried de novo mutations and the other 2 were maternal origin in the CHD2 gene. Of these, 3 were nonsense variants, 2 were missense variants and 1 was 3.58-Mb deletion including CHD2. Within the follow-up of 5 years to 15 years, 4 of the 5 patients were effective with regular ASM. Two patients achieved seizure-free more than 2 years, 1 patients achieved seizure-free more than 1 year and 8 months. Conclusion Epileptic seizures are common clinical phenotype of patients with CHD2 gene variants. The common seizure types include focal and generalized tonic-clonic seizures, and the age of onset of epilepsy varies widely. Patients with Jeavons syndrome have poor prognosis. Valproate may show a positive effect on epilepsy with CHD2 gene variation. Mental disorder is a rare clinical phenotype.

Key words: CHD2 gene, developmental and epileptic encephalopathy, epilepsy