CLCN4基因变异相关癫痫的临床表型及基因变异特点  

Phenotype and genotype of epilepsy patients related to CLCN4 variants

作　　者：张文荣 杨莹[1] 程苗苗 王婷 刘昌昊 杨小玲 张月华[1] Zhang Wenrong;Yang Ying;Cheng Miaomiao;Wang Ting;Liu Changhao;Yang Xiaoling;Zhang Yuehua(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China;Department of Pediatrics,Yan'an People's Hospital,Yan'an 716000,China)

机构地区：[1]北京大学第一医院儿科,北京100034 [2]延安市人民医院儿科,延安716000

出　　处：《中华神经科杂志》2024年第9期968-974,共7页Chinese Journal of Neurology

基　　金：北京市自然科学基金青年项目(7244420)。

摘　　要：目的:总结CLCN4基因变异相关癫痫患儿的临床表型及基因变异特点。方法:收集2016年12月至2024年3月在北京大学第一医院儿科诊治的9例通过家系全外显子组测序明确携带CLCN4基因变异的癫痫患儿,对其临床表现、脑电图及头颅影像学特点、治疗随访结果进行回顾性总结。结果:在9例患儿中,男性6例、女性3例。9例患儿CLCN4基因变异的类型均为新生变异,其中3例携带c.823G>A/p.V275M变异,2例携带变异c.2152C>T/p.R718W,1例携带变异c.1630G>A/pG544R,1例携带变异c.2167C>T/p.R723W,2例携带未报道的新变异c.848G>T/p.S283I及c.818G>A/p.G273E。9例患儿的癫痫起病年龄为55日龄至10岁,中位起病年龄为14月龄,其中2岁内起病者7例(7/9)。患儿癫痫发作类型多样,其中局灶性发作8例,全面强直阵挛发作1例,肌阵挛发作2例,癫痫性痉挛1例,不典型失神发作1例,其中3例有多种发作类型。9例均有全面发育落后,8例为全面发育落后,1例为认知发育落后,7例患儿在癫痫起病前已发现有发育落后。在9例患儿中,临床诊断为婴儿癫痫性痉挛综合征1例,不能分类的发育性癫痫性脑病7例,局灶性癫痫合并发育落后1例。9例患儿末次随访年龄为2岁5月龄至13岁9月龄,3例癫痫发作已缓解4~12个月。结论:CLCN4以新生变异常见,癫痫发作多数在婴儿期起病,发作类型多样,局灶性发作多见,表型轻重不一,多数有发育落后且为药物难治性癫痫,发育落后可出现在癫痫发作之前,符合发育性癫痫性脑病的特点。Objective:To summarize the clinical phenotypes and genetic variations of children with epilepsy related to CLCN4 gene mutations.Methods:A retrospective analysis was conducted on 9 children with epilepsy who were diagnosed with CLCN4 gene mutations through whole-exome sequencing of family members.These children were treated at the Department of Pediatrics,Peking University First Hospital from December 2016 to March 2024.Their clinical manifestations,electroencephalogram,cranial imaging characteristics,and treatment follow-up were reviewed.Results:Among the 9 children,6 were male and 3 were female.All cases involved de novo mutations.Three cases carried the c.823G>A/p.V275M variant,2 cases carried the c.2152C>T/p.R718W variant,1 case carried the c.1630G>A/pG544R variant,and 1 case carried the c.2167C>T/p.R723W variant.Two cases carried the unreported new variant c.848G>T/p.S283I and c.818G>A/p.G273E.The onset age of epilepsy ranged from 55 days to 10 years,with a median onset age of 14 months.Seven out of 9 children had epilepsy onset before the age of 2 years.The types of seizures varied:8 had focal seizures,1 had generalized tonic-clonic seizures,2 had myoclonic seizures,1 had epileptic spasms,and 1 had atypical absence seizures.Three children experienced multiple types of seizures.All 9 children exhibited developmental delays to varying degrees:8 had global developmental delay and 1 had cognitive developmental delay.Developmental delays were observed in 7 children before the onset of epilepsy.Clinically,1 child was diagnosed with infantile epileptic spasms syndrome,7 with unclassified developmental and epileptic encephalopathy,and 1 with focal epilepsy with developmental delay.At the last follow-up,the age of the children ranged from 2 years and 5 months to 13 years and 9 months.Seizures had been controlled in 3 children for a duration of 4 to 12 months.Conclusions:De novo variants are common in CLCN4 variants.Most seizures onset in infancy,seizure types are various,and focal seizures are common.Most of them hav

关 键 词：CLCN4基因 癫痫 发育落后 预后 

分 类 号：R742.1[医药卫生—神经病学与精神病学]