STXBP1-脑病19例病例系列报告  

Clinical and genotypic characteristics of 19 children with STXBP1-encephalopathy

作　　者：戚利那 姚海明 苗圃 冯建华[2] QI Lina;YAO Haiming;MIAO Pu;FENG Jianhua(Department of Pediatrics,Linping District,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 311100,Zhejiang,China;Department of Pediatrics,the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou 311100,Zhejiang,China)

机构地区：[1]浙江大学医学院附属第二医院临平院区儿科,浙江杭州311100 [2]浙江大学医学院附属第二医院儿科,浙江杭州311100

出　　处：《中国现代医生》2023年第35期23-26,53,共5页China Modern Doctor

基　　金：浙江省杭州市医药卫生科技计划项目(B20230024)。

摘　　要：目的总结STXBP1(syntaxin-binding protein1)基因突变所致的早期癫痫性脑病(early infantile epileptic encephalopathy,EIEE)临床表型和基因突变特征及二代基因测序在病因诊断中的应用。方法回顾性分析2017年1月至2021年1月在浙江大学医学院附属第二医院儿科就诊且基因诊断为STXBP1基因突变的19例癫痫性脑病患儿的临床特点、基因检测结果、治疗情况和疗效。结果15例(78.9%)患儿在出生后1个月内起病;19例患儿的脑电图均有明显的改变,其中爆发抑制13例(68.4%),高度心律失常12例(63.2%)。19例患儿中共检测出18个致病性变异位点,均为新发变异,其中有7个位点目前尚未见报道。5例患儿诊断为大田原综合征,5例患儿诊断为婴儿痉挛症,9例患儿为不能分类的癫痫性综合征。随访6个月至4年5个月,1例停药,5例癫痫发作完全缓解,6例部分缓解,7例无效。12例发作缓解或控制的患儿中有8例是通过联合左乙拉西坦治疗有效,6例痉挛发作的患儿加用氨己烯酸治疗后有4例有效,7例表现为药物难治性癫痫。19例患儿均存在不同程度的发育迟缓。结论智力、运动发育迟缓和癫痫反复发作是STXBP1-脑病主要的、独立的表型特征,STXBP1基因变异以新发变异为主,二代基因测序诊断有助于STXBP1-脑病的早期诊断,左乙拉西坦和氨己烯酸可能对控制STXBP1-脑病的癫痫发作部分有效,生酮饮食为早发性癫痫性脑病的治疗提供了新的思路。Objective To summarize the clinical phenotype and gene mutation characteristics of early epileptic encephalopathy caused by STXBP1 gene mutation and the application of second-generation gene sequencing in etiological diagnosis.Methods Retrospective analysis of clinical characteristics,gene test results,treatment and efficacy of 19 children with epileptic encephalopathy with genetic diagnosis of STXBP1 gene mutation who were seen in the Department of Pediatrics of the Second Hospital of Zhejiang University School of Medicine from January 2017 to January 2021.Results The disease started within 1 month after birth in 15 children(78.9%).All 19 children had significant electro-encephalo gram(EEG)changes:13 cases of burst suppression(68.4%)and high arrhythmia in 12 cases(63.2%).A total of 18 pathogenic variants were detected in 19 children,all of them new,of which 7 loci have not been reported so far.Five children were diagnosed with Otahara syndrome,five with infantile spasms,and nine with an epileptic syndrome that could not be classified.At a follow-up of 6 months to 4 years and 5 months,1 case was discontinued,5 cases had complete remission of seizures,6 cases had partial remission,and 7 cases were ineffective.8 of the 12 children with seizure remission or control were treated effectively with combination levetiracetam,4 of the 6 children with spasms responded with the addition of vigabatrin,and 7 presented with drug refractory epilepsy.All 19 children had varying degrees of developmental delay.Conclusion Mental-motor retardation and recurrent seizures are the main,independent phenotypic features of STXBP1-encephalopathy,STXBP1 gene variants are predominantly de novo variants,second-generation gene sequencing diagnosis helps in the early diagnosis of STXBP1-encephalopathy,levetiracetam and aminocaproic acid may be partially effective in controlling seizures in STXBP1-encephalopathy,and ketogenic diet provides new ideas for early-onset epileptic encephalopathy treatment provides a new idea.

关 键 词：STXBP1基因 STXBP1-脑病 儿童发育性癫痫性脑病 左乙拉西坦 基因诊断 

分 类 号：R47[医药卫生—护理学]