SCN8A基因突变致早发性婴儿发育性癫痫性脑病合并多发骨折2例及遗传学特征分析  

Clinical features and genetic analysis of two children with early infantile developmental and epileptic encephalopathies with multiple fractures caused by SCN8A mutation

作　　者：任蓉 史亚辉 张雷红 侯梅[1] 苑爱云[1] REN Rong;SHI Yahui;ZHANG Leihong;HOU Mei;YUAN Aiyun(Department of Neurorehabilitation,Affiliated Women’s and Children’s Hospital of Qingdao University,Qingdao,Shandong 266034,China)

机构地区：[1]青岛大学附属妇女儿童医院神经康复科,山东青岛266034

出　　处：《中国优生与遗传杂志》2024年第10期2137-2142,共6页Chinese Journal of Birth Health & Heredity

基　　金：青岛市2022年度医药卫生科研指导项目(2022-WJZD133)。

摘　　要：目的探讨2例SCN8A基因突变致早发性婴儿发育性癫痫性脑病(EIDEEs)并多发骨折的患儿的临床及遗传学特点。方法回顾性分析2例SCN8A基因杂合突变致EIDEEs合并多发骨折患儿的临床资料,并进行长达5年余随访。应用全外显子组测序分析患儿的致病基因,再用Sanger测序进行家系验证,复习相关文献,总结其临床特点、诊治经验及遗传学特征。结果病例1,女,生后1个月出现抽搐发作,11个月后发育落后,肌张力低,股骨发育异常,4岁后出现反复骨折、进行性小脑萎缩,检测提示SCN8A基因错义突变c.3967G>T(p.Ala1323Ser)。病例2,女,生后5小时出现抽搐发作,随年龄增长发现发育落后,肌张力障碍,2岁后出现反复骨折、进行性脑萎缩,检测提示为SCN8A基因错义突变c.1079T>C(p.Phe360Ser),此变异尚未见文献报道。2例患儿经Sanger测序家系验证均为新生突变。结论本研究在国内首次进行SCN8A基因突变导致EIDEEs和多发骨折的报道,发现新发错义突变位点1个,扩大了致病基因SCN8A的临床表型谱及变异谱。Objective This study aimed to explore the clinical and genetic characteristics of two infants with SCN8A gene mutations associated with early infantile developmental and epileptic encephalopathies(EIDEEs)and concurrent fractures,aiming to advance comprehension of this condition.Methods Clinical data from two cases of EIDEEs with compound heterozygous mutations in the SCN8A gene and multiple fractures were retrospectively analyzed,followed by a follow-up period exceeding 5 years.Whole exome sequencing(WES)was employed to investigate the pathogenic genes.Sanger sequencing was conducted for familial validation.A comprehensive literature review was conducted to summarize the clinical features,diagnostic and treatment experience and genetic characteristics.Results Case 1,female,seizures began at 1 month of age,followed by developmental regression at 11 months,hypotonia,and abnormal femoral development.Recurrent fractures and progressive cerebellar atrophy were observed at 4 years of age.Genetic testing identified a missense mutation c.3967G>T(p.Ala1323Ser)in the SCN8A gene.Case 2,female,seizures occurred within 5 hours after birth,followed by subsequent developmental delay and hypotonia.Recurrent fractures and progressive brain atrophy manifested after 2 years of age.Genetic testing confirmed a missense mutation c.1079T>C(p.Phe360Ser)in the SCN8A gene,not previously reported.Both patients harbored de novo mutations,validated through familial sequencing.Conclusion This study represents the first documentation in China of SCN8A gene mutations associated with EIDEEs and multiple fractures,elucidating a novel missense mutation site and expanding the clinical phenotypic spectrum and mutation spectrum of SCN8A gene.

关 键 词：SCN8A 早发性婴儿发育性癫痫性脑病 骨折 钠离子通道阻滞剂 全外显子组测序 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R726.8[医药卫生—临床医学]