Dravet综合征临床与SCN1A基因突变分析(附60例报告)

Clinical features and SCN1A mutation in 60 patients with Dravet syndrome

目的总结Dravet综合征(DS)临床诊治资料以及SCN1A基因检测结果,分析其特点,为临床提供参考。方法回顾性分析总结2013年12月至2015年12月复旦大学附属儿科医院神经科诊断的60例DS患儿临床资料、SCN1A基因报告及抗癫痫药物疗效。结果中位起病年龄6个月(1~9个月),其中83.3%(50/60)首次为热性惊厥,有热敏感特点,洗热水澡诱发63.3%(38/60)。临床有多种发作类型,全面强直阵挛发作占95.0%(57/60)、局灶性发作(左右交替单侧发作)占78.3%(47/60)、惊厥持续状态占65.0%(39/60)、肌阵挛发作占65.0%(39/60)和不典型失神发作占63.3%(38/60);1~3岁为发作高峰期(2~3次/月)。智力落后中位年龄为18个月;脑电图异常比例随年龄增长而增高。本组SCN1A基因突变率为80.0%(48/60),以错义突变和无义突变为主。患儿癫痫发作均表现为药物难治性癫痫。添加钠离子阻滞剂类药物导致发作加重者占40.0%(24/60),发作无改善及减轻者各占6.7%(4/60)。患儿起病年龄、性别、发作类型及频率与SCN1A基因突变类型差异无统计学意义(P>0.05)。结论 DS是儿童早发的癫痫性脑病,国内儿童癫痫中心并不罕见;DS的SCN1A基因突变阳性率高,可帮助DS诊断;DS抗癫痫药物治疗困难,误用药物比例高,仍须提高临床诊治水平。

Objective To study the clinical features and SCN1A genes detection results in children with Dravet syndrome in order to provide reference for clinical treatment. Methods The clinical data,SCN1A genes reports and antiepileptic drug effects of 60 DS children who were diagnosed from December 2013 to December 2015 were collected from the Children’s Hospital of Fudan University. Results The onset of seizures occured during 1-9 months with a median of 6 months and 83.3% of patients were febrile seizures at frist onset;they were heat sensitive,and hot water bath induced seizures in 63.3%（38/60）. There were multiple phenotypes,including generalized tonic-clonic seizures（95.0%,57/60）,partial seizures（alternating unilateral seizure）（78.3%,47/60）,status epilepticus（65.0%,39/60）,myoclonic seizures（65.0%,39/60）,and atypical absence （63.3%,38/60）. Seizure ouccurred most frequently（2-3 times per month） in 1-3 years of age. The median age of mental retardation was 18 months. The number of mental retardation and the positive rate of EEG increased with age. Dravet syndrome were intractable. In patients who used sodium ion blocking drugs 40.0%（24/60） children had aggravated seizures. 80.0%（48/60） patients had SCN1A mutation with missense and nonsense mutation accounting for over a half. There was no correlation between SCN1A mutations and onset age,sex,seizure type or seizure frequency. Conclusion Dravet syndrome is a childhood-onset epileptic encephalopathy,which is not rare in the national seizure center. The positive rate of SCNIA mutation is high,which can help the diagnosis of DS. Anti-epiletic drug treatment for DS is difficult and the misuse of drugs is in a high proportion,so the diagnosis and treatment level still needs to be improved.