NBEA基因变异相关癫痫性脑病1例并文献复习

Epileptic Encephalopathy Associated with NBEA Gene Mutation: A Case Report and Literature Review

摘要: 目的：探讨NBEA基因变异相关癫痫性脑病患儿的临床及遗传学特点。方法：回顾性分析1例NBEA基因变异相关癫痫性脑病患儿的病例资料，分析其临床表型及基因变异特点，并以“NBEA”“neurokeratin”“epilepsy”“epileptic encephalopathy”“癫痫”“癫痫性脑病”为关键词分别检索PubMed、中国知网、万方数据库，总结NBEA基因变异相关癫痫性脑病患儿的临床及遗传学特点。结果：患儿，男，1岁5个月，因“抽搐发作1月余”就诊，临床表现为肌阵挛发作、痉挛发作，发病前智力运动发育正常，癫痫发作后语言和运动发育明显倒退。家系全外显子组基因测序提示患儿NBEA基因杂合无义变异c.8398A>T(p.Lys2800*)。口服左乙拉西坦、托吡酯联合吡仑帕奈抗癫痫发作治疗后，癫痫发作控制，发育较前有进步。文献检索到5篇文献(1篇中文，4篇英文)共报道了24例(包含本例)NBEA基因变异相关癫痫性脑病患儿，多数患儿表现为难治性癫痫，均有不同程度的智力障碍/发育迟缓，语言发育迟滞明显，部分患儿合并孤独症谱系障碍。共发现24个变异位点，变异类型大多数为功能丧失变异。结论：NBEA基因变异相关癫痫性脑病预后不佳，对于难治性癫痫、发育迟缓(尤其是语言发育迟缓)、孤独症样表现的患儿，需警惕NBEA基因变异相关癫痫性脑病，进行基因检测有助于明确诊断。

Abstract: Objective: To investigate the clinical and genetic features of epileptic encephalopathy associated with NBEA gene variants. Methods: The clinical data of a child with epileptic encephalopathy associated with NBEA gene variation were retrospectively analyzed, and the characteristics of clinical phenotype and gene mutation were analyzed. “NBEA”, “neurokeratin”, “epilepsy”, “epileptic encephalopathy” and “epileptic encephalopathy” were used as keywords to search PubMed, CNKI and Wanfang database, respectively, to summarize the clinical and genetic features of epileptic encephalopathy associated with NBEA gene variants. Results: The boy, aged 1 year and 5 months, was admitted to the hospital due to myoclonic seizures and spasms for more than 1 month. His mental and motor development was normal before the onset of seizures, but his language and motor development regressed significantly after seizures. Whole exome sequencing revealed a heterozygous nonsense variant c.8398A>T(p.Lys2800*) in the NBEA gene. After oral administration of levetiracetam, topiramate and pirampanide, the seizures were controlled and the development was improved. Literature review identified 5 articles (1 in Chinese and 4 in English) that reported 24 cases of NBEA gene variants associated with epileptic encephalopathy (including this case). Most of the patients presented with intractable epilepsy, varying degrees of intellectual disability/developmental delay, with significant language delay, and some patients were complicated with autism spectrum disorder. A total of 24 variants were found, most of which were loss-of-function variants. Conclusions: NBEA gene variants associated with epileptic encephalopathy have a poor prognosis. Children with intractable epilepsy, developmental delay (especially language delay) and autism-like manifestations should be considered for NBEA gene variants associated with epileptic encephalopathy.