钠离子通道基因突变相关儿童癫痫脑病患儿的临床特点及遗传学分析

Clinical features and sodium channel gene mutations analysis of children with epileptic encephalopathy

目的:探讨总结Na^(+)通道基因突变相关儿童癫痫性脑病患儿的临床和基因突变特点。方法:采集2017年11月至2019年12月就诊于湖南省儿童医院神经内科的不明原因癫痫性脑病患儿及其父母外周血,应用靶向捕获二代测序方法进行基因测序分析,并应用Sanger测序对变异及来源进行验证,筛选出20例Na^(+)通道基因阳性突变的患儿,收集其临床资料,对其临床特征、基因突变、治疗及随访情况进行分析总结。结果:20例Na+通道基因突变相关儿童癫痫脑病患儿中女性7例,男性13例,起病年龄2 d至10个月。14例为SCNlA基因突变,5例为SCN2A基因突变,1例为SCN8A基因突变,均为新生突变。其中,14例临床诊断为Dmvet综合征(DS),2例诊断为大田原综合征(OS),4例诊断为不能分类的儿童癫痫脑病。20例患儿给予多种抗癫痫药物治疗,随访6〜63个月,9例癫痫发作未控制(其中1例夭折),7例癫痫发作部分控制,4例癫痫发作控制,所有患儿均有智力及运动发育落后。结论:Na^(+)通道基因突变是儿童癫痫性脑病常见的遗传性病因,Na^(+)通道基因突变可引起不同表型癫痫脑病.基因检测可明确病因诊断,并为精准治疗提供依据。

To summarize the clinical features and gene mutation characteristics of chil clren with epileptic encephalopathy(EE)associated with sodium ion channel gene mutation.Methods:The peripheral blood of children with unexplained EE treated in the Department of Neurology of Hu nan Children’s Hospital from November 2017 to December 2019 were collected,and the peripheral blood of their parents were also collected.Next generation sequencing was used to detect epilepsy-re lated genes,and Sanger sequencing was performed to confirm the result of mutation and its source.The clinical data and gene mutations of 20 cases with EE caused by sodium ion channel gene mutation were analyzed and summarized.Results:All the 20 cases(7 girls and 13 boys)with different heterozy,gous mutations of sodium ion channel gene mutation belonged to de novo mutation,including 14 cases with SCN8A mutation,5 with SCN2A mutation,and 1 with SCN8A mutation.The age of onset was from 2 days to 10 months.Among them,14 cases were clinically diagnosed as Dravet syndrome(DS),2 cases as Ohtahara syndrome(OS),and 4 cases as nonspecific EE.After treatment with a variety of antiepileptic drugs,the clinical seizures in 4 cases were under control,and seizures were partially con trolled in 7 cases.But the prognosis of 9 cases were poor,and the seizures were out of control,(one of them died).All the 20 patients had retardation of intelligence and motor development.Conclusion:Sodium channel gene mutation is a common genetic cause of EE in children.Sodium channel gene mu­tation can cauvse different phenotypes of EE.Gene detection can clarify etiological diagnosis and pro­vide basis for precise therapy.