CHD2基因相关新生儿期癫痫性脑病1例并文献复习

目的 探讨CHD2基因相关的癫性脑病发病年龄与基因型关联性特点,提高CHD2致病变异可致早期癫性脑病的临床认识。方法 对复旦大学附属儿科医院收治的1例新生儿癫性脑病患儿进行临床表型及基因型分析。以“CHD2基因”为关键词,检索中国知网、维普数据库和万方数据库, 以“CHD2”为基因名称检索HGMD数据库,并以“CHD2 gene”为关键词检索PubMed、Web of Science数据库,检索时间为建库至2018年11月29日,总结CHD2缺陷致癫性脑病的临床特征及遗传学特点。结果 患儿男,在新生儿期表现为惊厥发作、肌张力异常及喂养困难,全外显子测序分析提示CHD2基因存在新发可能致病变异［NM_001271:exon31:c.3951G>C(p.L1317F)］。文献检索目前国内外已报道CHD2基因致病病例67例,均尚未见新生儿期出现明显神经系统异常表现,但61.1%（11/18）病例存在癫起病前神经发育障碍的病史。结合已报道病例及本文病例,癫首次发作年龄为6个月以内（含6个月）共3例,均为错义突变;首次发作年龄6个月以上19例,其中5例为错义突变（26.3%）。结论 CHD2基因缺陷致癫性脑病可在新生儿期即出现惊厥发作。CHD2基因的错义变异可能有引起癫早期发作的倾向。仅表现为神经发育障碍,而无癫发作的患儿,也应考虑可能携带CHD2致病变异的可能性。

CHD2 gene related neonatal epileptic encephalopathy: 1 case report and literature review

Objective We aimed to analyze the onset age and genotype of CHD2-related epileptic encephalopathy and to improve the understanding that the disease can occur in the neonatal period. Methods We analyzed one newborn with epileptic encephalopathy admitted to Children's Hospital of Fudan University. We searched the gene "CHD2" in HGMD database and key words including "CHD2 gene" in CNKI, VIP database, Wanfang database, PubMed and the Web of Science database. All of the databases were searched up to Nov 29, 2018. Results The male newborn in the hospital mainly presented with seizures, dystonia and feeding difficulties. A de novo mutation［NM_001271:exon31:c.3951G>C(p.L1317F)］was detected in CHD2 gene. We reviewed 67 cases from Chinese and foreign literature databases. None of the reported cases had seizures during the neonatal period. Sixty-one point one percent (11/18) of cases showed developmental delay before the onset of seizures. According to the reported cases and the case from this study, we found that all of the three cases who presented with seizures within 6 months (including 6 months old) carried missense variants of CHD2 (3/3,100%), and 5 of 19 cases (5/19,26.3%) occuring seizures at the age of older than 6 months carried missense variants. Conclusion The defected CHD2 can cause epileptic encephalopathy in the neonatal period. The missense variants of CHD2 may have a tendency to cause early epilepsy. Defected CHD2 should be taken into consideration for patients with neurodevelopmental disorders and no seizures.