Na^(+)通道阻滞剂治疗SCN2A基因变异所致早发型癫痫性脑病并文献复习

Na^(+) channel blockers in treatment of early-onset epileptic encephalopathy caused by SCN2A gene variation:a case report and literature review

目的探讨Na^(+)通道阻滞剂治疗SCN2A基因变异所致早发型癫痫性脑病(EOEE)的临床特点及预后。方法选择2015年11月24日,在深圳市儿童医院确诊为EOEE的1例男性患儿为研究对象,确诊时月龄为4个月。采用回顾性分析方法,对其临床特点、基因检测结果、治疗方案及随访结果进行分析。对中国知网数据库、万方数据知识服务平台及PubMed数据库中,对SCN2A基因变异致EOEE患儿相关研究文献进行检索,总结SCN2A基因变异致EOEE患儿的临床及遗传学特点。本研究遵循的程序符合2013年新修订的《世界医学协会赫尔辛基宣言》要求,并与本例患儿监护人签署临床研究知情同意书。结果①病史采集:本例患儿生后第3天开始出现反复惊厥发作,表现为强直阵挛发作,局灶性阵挛发作及痉挛发作,癫痫持续状态,并伴发育落后。采取多种抗癫痫药物对其治疗后,疗效不佳。②辅助检查结果:本例患儿脑电图检查结果呈缺氧性癫痫性脑病的爆发抑制状况;基因检测结果为SCN2A基因错义突变NM_001040143:c4886G>A(pArg1629His),患儿父亲及母亲该位点均未见异常;头部MRI结果提示右侧脉络膜裂囊肿。③治疗及转归:对本例患儿加用奥卡西平治疗后,无惊厥发作,脑电图复查结果提示仍有少量癫痫样放电,智力发育迟缓状况逐步好转。④根据本研究设定的文献检索策略,共检索到关于该病患儿研究相关的中、英文文献分别为4、7篇,涉及44例发生SCN2A基因变异所致EOEE患儿。结论对于EOEE患儿应及时完善基因检测。明确EOEE致病基因后,对患儿及时采用针对致病基因的精准治疗方案可控制惊厥发作,降低患儿脑损害,改善患儿预后。

Objective To explore clinical characteristics and prognosis of Na^(+) channel blockers in treatment of early-onset epileptic encephalopathy(EOEE)children caused by SCN2A gene variation.Methods One boy with EOEE diagnosed at Shenzhen Children′s Hospital on November 24,2015,whose age was 4 months at the time of diagnosis,was selected into this study.The clinical features,genetic test results,therapeutic regimen and follow-up results of this boy were analyzed retrospectively.By searching relevant literature on research of children with EOEE caused by SCN2A gene variation in China National Knowledge Infrastructure,Wanfang database,and PubMed,their clinical data and genetic characteristics were summarized.The procedure followed in this study was in line with the requirements of the Helsinki Declaration of the World Medical Association revised in 2013.Informed consent for clinical research was obtain from guardians of this boy.Results①This boy began to have repeated convulsive epileptic seizures on the third day after birth,showing tonic-clonic seizures,focal clonic seizures and spastic seizures,and complication of developmental retardation.The therapeutic effects of combination of various antiepileptic drugs were poor.②The electroencephalogram results of this boy suggested burst suppression of anoxic epileptic encephalopathy;the genetic test showed a missense mutation in SCN2A gene with NM_001040143:c4886G>A(pArg1629His),and neither his father nor his mother showed any abnormality in SCN2A gene;result of head MRI of this boy suggested a right choroidal fissure cyst.③This boy was treated with oxcarbazepine up to his convulsive epileptic seizures had disppeared thoroughly.The electroencephalogram reexamination results showed there was still a small amount of epileptiform discharge,and his mental development gradually improved.④According to literature retrieval strategies set in this study,4 Chinese and 7 English articles with a total of 44 EOEE children caused by SCN2A gene variants were published.Conclusions Genetic testing for EOEE children should be completed in time.After identifying pathogenic gene of EOEE,timely precise treatment of pathogenic gene for EOEE children can control convulsive epileptic seizure,reduce brain damage of EOEE children and improve their prognosis.