19例儿童Dravet综合征临床特点及分子遗传学分析  

Clinical characteristics and molecular genetic study of 19 patients with Dravet syndrome

作　　者：李永利[1] 廖建湘[1] 邹东方[1] LI Yong-li;LIAO Jian-xiang;ZOU Dong-fang(Department of Neurology,Shenzhen Children’s Hospital,Shenzhen 518038,Guangdong,China)

机构地区：[1]深圳市儿童医院神经内科,广东深圳518038

出　　处：《生物医学工程与临床》2021年第4期482-487,共6页Biomedical Engineering and Clinical Medicine

基　　金：深圳市科技创新委员会科技应用示范项目(KJYY20151116165726645)。

摘　　要：目的研究Dravet综合征(DS)的临床和分子遗传学特点,为临床早期诊断及治疗提供帮助。方法选择2015年1月至2019年3月在深圳市儿童医院诊治的19例DS患儿,其中男性12例,女性7例;年龄1~10岁,中位年龄3.2岁。抽取患儿及其父母外周血,采用二代测序癫痫基因检测包对临床诊断病例进行检测。所有患儿采用2种或以上抗癫痫药物口服,其中8例采用生酮饮食治疗。结果首次发作年龄3~11个月(中位年龄6.6个月);以热性惊厥起病14例(74%),癫痫持续状态9例(47%);1岁后出现多种发作形式,局灶性发作19例(100%),半侧阵挛15例(79%),肌阵挛13例(68%),全面性强直阵挛8例(42%),不典型失神3例(16%)。脑电图(EEG)在发作间期可监测到全导或局灶棘慢复合波阵发,起病初期未见异常12例(63%),经生酮饮食治疗后明显改善4例(50%,4/8)。基因检测结果,编码电压门控钠离子通道α1亚单位(SCN1A)基因变异14例(74%),包括错义变异(64%,9/14)、无义变异(21%,3/14)、移码变异(7%,1/14)和剪接变异(7%,1/14),均为De novo变异;编码电压门控钠离子通道α2亚单位基因(SCN2A)错义变异1例,原钙黏蛋白编码基因19(PCDH19)错义变异和无义变异各1例,检测阴性2例。结论DS起病年龄早,多以长时程热性惊厥起病,发作形式多样,EEG与临床发作严重程度呈不平行发展;SCN1A变异是DS的主要原因,基因检测有助于早期诊断及提供治疗决策。Objective To explore clinical and molecular genetic characteristics of Dravet syndrome(DS),and provide comprehensive reference for early and precise diagnosis,as well as treatment of DS.Methods From January 2015 to March 2019,19 children with DS were enrolled,which included 12 males and 7 females,aged 1-10 years old with median age of 3.2 years old.The peripheral blood of the children and their parents were drawn and tested using next-generation sequencing epilepsy genetic test kit.All of the children were orally administrated with two or more kinds of anti-epileptic drugs,and 8 of them were treated with ketogenic diet.Results The test results showed that the first onset age was 3-11 months with median age of 6.6 months.Onset of febrile seizures was first observerd in 14 cases(74%),status epilepticus in 9 cases(47%).After one year,there were multiple types of seizures,which included focal seizures in 19 cases(100%),hemilateral clonus in 15(79%),myoclonus in 13(68%),generalized tonic-clonus in 8(42%)and atypical absence in 3(16%).Interictal electroencephalogram(EEG)detected showed total or focal spike-slow complex wave bursts.There were no abnormalities in 12 cases(63%)at initial stage of onset,and 4 cases(50%,4/8)were significantly improved after ketogenic diet treatment.The results of gene tests showed that 14 cases(74%)were gene variants of encoding voltage-gated Na+channelα1 subunit(SCN1A),which included missense mutations(64%,9/14),nonsense mutations(21%,3/14),frameshift mutations(7%,1/14)and splicing mutations(7%,1/14),and they all were De novo mutation.Besides,1 was encoding the alpha 2 subunit gene of the sodium channel(SCN2A)missense mutation,1 was procadherin encodes gene 19(PCDH19)missense and 1 was PCDH19 nonsense mutation,and 2 were negative.Conclusion It is demonstrated that DS usually manifests early onset-age of prolonged febrile seizures and multiple types of other seizures.The severity of EEG abnormality is not parallel to severity of clinical seizure onset.SCN1A mutation is the main cause of DS

关 键 词：癫痫 DRAVET综合征 SCN1A基因 脑电图 

分 类 号：R742.1[医药卫生—神经病学与精神病学]