Abstract:

Objective: To report clinical characteristics of Lennox-Gastaut syndrome (LGS) caused by CHD2 gene de novo variation. Methods and Results: Three children with LGS admitted to Peking University People's Hospital from June 2023 to May 2024 were enrolled. Their onset ages were 3 months, 3 years and 4 months, and 3 years and 5 months, respectively. All 3 cases were transformed from infantile spasms (IS), presenting with spasm epileptic seizures, tonic seizures and global developmental delay. EEG initially showed hypsarrhythmia, which later progressed to generalized and multifocal discharges during disease progression. Whole exome sequencing (WES) revealed a missense variant c. 2740C > T (p. Arg914Cys) in Case 1, a nonsense variant c. 806C > G (p. Ser269*) in Case 2, and a missense variant c.2492A > C (p.His831Pro) in Case 3; neither parent carried the same type of variation, all variants were de novo. Three patients received antiepileptic seizure medicine (ASM), and at the last follow-up, seizures remained uncontrolled in all patients. Conclusions: LGS caused by CHD2 gene variation typically present in childhood, often with delayed motor and language development. Most patients have uncontrollable seizures that are often resistant to medication.

Key words: Lennox Gastaut syndrome, Epilepsy, Genes, Mutation, Child, preschool

摘要：

目的: 报道3例CHD2基因新发变异致Lennox-Gastaut综合征患儿，总结其临床和遗传学特征。方法与结果: 选择北京大学人民医院2023年6月至2024年5月收治的3例Lennox-Gastaut综合征患儿，发病年龄分别为3个月、3岁4个月和3岁5个月，均为婴儿痉挛症进展为Lennox-Gastaut综合征，均存在痉挛发作、强直发作及全面发育迟缓；脑电图呈高度失律，随病情进展表现为广泛性及多灶性放电。全外显子组测序显示，例1存在CHD2基因c.2740C > T（p.Arg914Cys）错义突变，例2存在CHD2基因c.806C > G（p.Ser269*）无义突变，例3存在CHD2基因c.2492A > C（p.His831Pro）错义突变，父母均未携带同型突变，均为新发突变。予以抗癫痫发作药物，其中例3同时予生酮饮食，但均未控制发作。结论: CHD2基因变异致Lennox-Gastaut综合征通常于儿童期发病，常伴运动、语言发育迟缓，多数癫痫发作难以控制。

关键词: 伦诺克斯综合征, 癫痫, 基因, 突变, 儿童，学龄前