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中国循证儿科杂志

中国循证儿科杂志 ›› 2018, Vol. 13 ›› Issue (4): 280-284.

• 论著 • 上一篇    下一篇

STXBP1基因突变致癫性脑病8例病例系列报告

路通1),杜晓楠1),吴冰冰2),周浩1),李春培1),王艺1)   

  1. 复旦大学附属儿科医院 上海，201102；1）神经内科，2）分子医学中心
  • 收稿日期:2018-02-05 修回日期:2018-08-25 出版日期:2018-08-25 发布日期:2018-08-25
  • 通讯作者: 王艺

Report of 8 epileptic Encephalopathy cases caused by STXBP1 gene mutations and literature review

LU Tong1) ，DU Xiao-nan1) ，WU Bing-bing2) ，ZHOU Hao1) ，LI Chun-pei1) ，WANG Yi1)   

  1. Children's Hospital of Fudan University, Shanghai 201102, China；1) Department of Neurology, 2) Center of Molecular Medicine
  • Received:2018-02-05 Revised:2018-08-25 Online:2018-08-25 Published:2018-08-25
  • Contact: WANG Yi

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摘要： 目的 总结STXBP1基因突变所致的癫性脑病的临床表现及基因突变特点。方法 回顾性分析2011年12月30日至2018年1月31日于复旦大学附属儿科医院就诊且基因诊断为STXBP1基因突变的癫性脑病患儿的临床特点、基因检测结果、治疗和疗效。结果 8例STXBP1基因突变致癫性脑病患儿进入本文分析，男、女各4例，起病年龄为生后2 d至6月龄（中位数为生后15 d）。8例均存在发育落后，均有不同程度的反应欠佳、眼示踪较差，2例角弓反张，1例皮肤黝黑、阴囊着色较深。脑电图波形：4例为暴发抑制，3例为高峰失律，1例为两侧较多痫样放电。2例行DST（智力及发育筛查），DQ（发育商）和MI（智商指数）均<50。1例合并先天性喉软骨发育不良，腹部B超示肾上腺皮质均质性增大。1例合并孤独症。8例共检测到7个STXBP1基因突变位点，其中错义突变4个，无义突变2个，移码突变1个。c.1216C>T (p.R406C)、c.246G>A（p.K82K）、c.1702G>A(p.G568S)和 c.54delG位点此前未被人类基因突变数据库(HGMD)收录，经软件预测均为有害突变；c.1439C>T（p.P480L）、c.585 C>G( p.Y195X)和c.1162C>T（p.R388X）为HGMD已收录的致病位点。4例诊断为大田原综合征，3例为WEST综合征，1例为不能分类的癫综合征。经过单药或联合治疗，5例得到临床发作控制，3例表现为药物难治性癫。结论 STXBP1基因突变相关的癫性脑病是严重的儿童神经系统疾病，肾上腺增大可能为其新的表型之一。

Abstract: Objective To investigate the clinical and genetic features of epileptic encephalopathy caused by STXBP1 mutations. Methods The patients with epileptic encephalopathy caused by STXBP1 mutations were recruited from December 30, 2011 to January 31, 2018 in our hospital, and their gene data and clinical data including treatment and outcome were analyzed. Results There were 8 children (4 females and 4 males) in this study. The onset age ranged from 2 d after birth to 6 months, and the mean age was 15 days. All the patients had moderate to severe development delay, poor reaction and eye chasing. Two patients had opisthotonos, and 1 patient was observed with dark skin especially on the scrotum. The EEG abnormalities were burst-suppression pattern in 4 cases and hypsarrhythmia in 3 cases, and multifocal discharges on both side in 1 case. DST was checked on 2 patients. DQ<50 and MI<50 in both of them. One patient had laryngomalacia and adrenal glands enlargement. One male was clinical diagnosed with ASD. Seven mutation sites were detected: 5 missense mutations, 1 deletion mutation，and 2 nonsense mutations. Mutations of c.1216C>T (p.R406C)，c.246G>A(p.K82K), c.1702G>A(p.G568S) and c.54delG were novel and were predicted as harmful. The mutations of c.1439C>T(p.P480L)， c.585 C>G(p.Y195X) and c.1162C>T(p.R388X) were recorded in Human Gene Mutation Datebase (HGMD). Four cases were diagnosed with Ohtahara syndrome and 3 were WEST syndrome, while the initial phenotype of 1 patient did not fit into a specific recognized epilepsy syndrome. Seizures were well controlled with AEDs in 5 cases with 1 or 2 combined anti-epilepsy medicine. Three patients were refractory. Conclusion STXBP1-related epileptic encephalopathy is a severe neurological disorder. Adrenal glands enlargement may be a new phenotype associated with epileptic encephalopathy.