Abstracts

Rationale: Chromodomain helicase DNA-binding (CHD) protein family, which consist of nine members distinguished by structural differences, is known as chromatic remodeler, regulating the structure of chromatin and ultimately affecting gene expression. CHD2 is a member of CHD protein family, and the pathogenic variants in CHD2 gene have been reported to be associated with brain-restricted phenotypes in human, particularly, developmental epileptic encephalopathy.


Methods: Among the patients who performed customized gene panel study, which contains 172 genes related to developmental and epileptic disease, in a single tertiary medical institution in Korea, 21 patients with pathogenic/likely pathogenic variants in CHD2 gene was identified. Excluding two patients with insufficient clinical data, 19 patients were included in this study. Retrospective review of medical records was conducted, including demographic, clinical, radiological, and electroencephalographic characteristics.


Results: Eighteen pathogenic/likely pathogenic variants, including 12 novel variants, were identified in 19 individuals. They included 9 nonsense variants (50%), 5 splicing sites variants (27.8%), and 2 missense variants (11.1%). Two were large deletion, skipping one or more exons. All patients manifested epilepsy with a median age of 2 years (range 0.42 – 6.75 years) at onset. Accompanying clinical presentations other than epilepsy were observed in 18 patients, including intellectual disability (12/19, 63.2%), global development delay (11/19, 57.9%), and behavioral disorder (4/19, 21.1%). The history of febrile convulsions was found in 11 patients (68.4%). Fourteen (73.7%) patients presented generalized seizure, 3 (15.8%) presented focal seizure, and 2 (11%) patients showed both generalized and focal seizure. Regarding response treatment, 14 patients (73.7%) achieved seizure-free status with anti-seizure medication, and one (5.3%) showed 50% reduction of seizure frequency. Two patients who carried identical variant showed distinctive clinical features, including onset age, seizure semiology, and electroencephalography findings. Additionally, in a patient who carried a deletion of Exon 5, paternal inheritance was revealed through trio test. However, her father was asymptomatic.


Conclusions: Epilepsy was the most common clinical manifestation in CHD2-related disease, with various accompanying neurological deficits. The discrepancy between the genotype and clinical characteristics was observed in this study. Further research on phenotype-genotype correlation is warranted.


Funding: none