KCNT1基因变异导致的早发性癫痫脑病患儿遗传学和临床分析  

Genetic and clinical analysis of children with early-onset epilepsy encephalopathy caused by KCNT1 gene mutation

作　　者：陈岩[1] 包新华[1] 章清萍[1] 王佳平 文泳欣 于淑杰 赵滢[1] Chen Yan;Bao Xinhua;Zhang Qingping;Wang Jiaping;Wen Yongxin;Yu Shujie;Zhao Ying(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院儿科,100034 [2]哈尔滨市儿童医院

出　　处：《中华儿科杂志》2018年第11期824-828,共5页Chinese Journal of Pediatrics

基　　金：985北京大学临床医院合作专项 （2013-1-06） ;吴阶平医学基金 （320.6750.17091）;哈尔滨市科技创新人才研究专项资金项目 （2016RAXYJ089）

摘　　要：目的研究早发性癫痫脑病患儿的KCNT1基因变异与临床特点。方法回顾性分析自2012年1月至2017年12月在北京大学第一医院儿科就诊的175例早发性癫痫脑病患儿的临床资料，应用靶向捕获二代测序方法，对患儿外周血进行基因变异分析，并应用PCR-Sanger对变异及来源进行验证。对KCNT1基因变异患儿的临床特点进行归纳总结。结果在175例早发性癫痫脑病患儿中，发现6例（男4例，女2例）患儿具有KCNT1变异，均为新发变异，占总病例的3.4%（6/175），变异类型均为错义变异。6例患儿的发病年龄为2-32 d。5例患儿诊断为婴儿癫痫伴游走性局灶性发作，1例诊断为癫痫，局灶性发作，局灶性发作伴泛化。6例患儿均应用多种抗癫痫药物，4例部分有效，2例发作无明显减少，后者中1例患儿于1岁4个月因＂重症肺炎＂死亡。4例患儿应用奎尼丁治疗，3例发作无减少，1例发作减少后再次出现复发,该患儿曾使用生酮饮食效果不理想。5例患儿应用生酮饮食治疗，无明显效果。6例患儿均不能独坐，追光、追物欠佳，均无语言。结论175例早发性癫痫脑病中发现KCNT1基因变异6例，以新发错义变异为主；患儿起病年龄多在新生儿期与婴儿期早期，以婴儿癫痫伴游走性局灶性发作为主要发作形式。智力、运动发育严重落后。抗癫痫药物治疗效果欠佳，奎尼丁疗效不显著，尚需大样本的治疗研究进一步评估其疗效。ObjectiveTo study the mutational characteristics of KCNT1 and its clinical features in children with early-onset epileptic encephalopathy.MethodsRetrospective analysis of clinical data of 175 children with early onset epilepsy from the Department of Pediatrics at Peking University First Hospital from January 2012 to December 2017. Gene-based analysis was performed on children with targeted capture second-generation sequencing and the source of mutations was verified by PCR-Sanger. The clinical features of children with KCNT1 mutation were summarized.ResultsIn 175 infants with early-onset epileptic encephalopathy, 6 children were found to have KCNT1 mutations, all of which were new mutations with an overall mutation rate of 3.4% （6/175）. All the mutations were missense mutations. The age of onset was from 2 days to 32 days. Five children were diagnosed with epilepsy of infancy with migrating focal seizure, one case was diagnosed with epilepsy, focal seizures, focal seizures with generalization. A total of 6 children were treated with multi-antiepileptic drugs. The disease in 4 patients were partially controlled, while in 2 patients, the disease was not significantly alleviated. One patient died of ＂severe pneumonia＂ at one year and 4 months of age. Then, four cases were treated with quinidine. The seizure frequency had no change in 3 cases, the frequency decreased and then relapsed in 1 case. The case once ketogenic diet and failed. Ketogenic diet treatment was applied to 5 cases, no significant effect was achieved. All the 6 patients had severe developmental delay. They could not sit alone, follow the light and objects and had no language.ConclusionsThe mutation of KCNT1 gene is mainly de novo. The onset of the disease was early, and mostly occurs in neonate and early infancy. The main seizure type was epilepsy of infancy with migrating focal seizure. Patients usually had severe psychomotor developmental delay. Antiepileptic drugs are ineffective. The efficacy of quinidine was not significant. Though, it

关 键 词：癫痫 基因 奎尼丁 

分 类 号：R742.1[医药卫生—神经病学与精神病学]