NEXMIF基因新发变异致West综合征患儿1例的临床及遗传学分析

Clinical and genetic analysis of a child with West syndrome due to a de novo variant of NEXMIF gene

目的:探讨1例NEXMIF基因变异所致West综合征患儿的临床特征及基因变异情况。方法:以1例2021年3月就诊于解放军总医院第一医学中心儿科的患儿作为研究对象。收集患儿的临床资料,对患儿及其父母进行全外显子组测序,对候选变异进行Sanger测序验证及致病性分析。总结患儿的治疗情况。结果:患儿为男性,出生4个月时无明显诱因出现成串痉挛发作,视频脑电图提示异常,高度失律,监测到数次成串痉挛发作。头颅磁共振成像提示额顶部脑外间隙增宽。查体发现患儿不会竖头、追听、追视,小头畸形,身高<1 SD,在当地医院诊断为West综合征,予泼尼松口服3个月后癫痫发作得到控制,调整为托吡酯片口服,已有7个月未发作。测序发现患儿携带NEXMIF基因c.982_c.983delTT(p.L328Dfs*23)新发无义变异。结论:对以严重发育落后甚至倒退为首发症状、癫痫发作难以控制且伴有异常面容的West综合征患儿,需警惕NEXMIF基因变异。基因检测有助于早期诊断及治疗。

Objective To investigate the clinical features and genetic variant of a child with West syndrome due to a variant of NEXMIF gene.Methods A child who was admitted to Department of Pediatrics,the First Medical Center of Chinese PLA General Hospital in March 2021 was selected as the study subject.Clinical data of the patient was collected.The child and his parents were subjected to whole exome sequencing.Candidate variant was verified by Sanger sequencing and pathogenicity analysis.Results The child,a 4-month-old boy,had presented with spastic seizures with no obvious cause.Abnormal EEG,severe hypsarrhythmia,and multiple spastic seizures were discovered.Cranial MRI revealed widening of the extracerebral space at the top of the frontal lobe.Physical examination revealed that he could not hold his head up,and could not respond to sounds or follow objects with eyes.He also has microcephaly,with height<1 s.The child was diagnosed with West syndrome at a local hospital,and given prednisone orally for 3 months,with seizures under control.Topiramate tablets were taken orally for maintenance treatment,and he has been seizure-free for 7 months.DNA sequencing revealed that he has harbored a de novo nonsense variant of c.982_c.983delTT(p.L328Dfs*23)in the NEXMIF gene.Conclusion For children with West syndrome with severe developmental delay or even regression as the first symptoms,uncontrollable seizures and abnormal facial appearance,mutations in the NEXMIF gene should be suspected,and genetic testing can facilitate early diagnosis and treatment.