DYNC1H1导致婴儿癫痫性痉挛综合征2例并文献复习

DYNC1H1-related infantile epileptic spasms syndrome:two cases report and literature review

目的报道2例DYNC1H1基因异常导致婴儿癫痫性痉挛综合征(IESS)患儿的临床特点、诊治过程并进行文献复习。方法回顾性分析2例解放军总医院第一医学中心住院治疗的DYNC1H1基因突变相关IESS患儿的临床资料,检索PubMed、在线人类孟德尔遗传数据库(OMIM)、中国知网、万方数据知识服务平台等数据库,结合文献总结DYNC1H1基因突变相关IESS患儿的临床特点,探讨其治疗及表型-基因关系。结果2例DYNC1H1变异相关的IESS患儿(病例1:c.874C>T,p.Arg292Trp;病例2:c.5884C>T,p.Arg1962Cys),痉挛发作均起始于婴儿期,多种药物控制效果均不佳。2例患儿均存在严重的发育迟缓,且病例1的头颅磁共振成像提示巨脑回畸形。搜索数据库并手动筛选共获得英文文献7篇,中文文献2篇。共15例DYNC1H1基因突变相关婴儿痉挛症,12例发展为药物难治性癫痫;12例存在显著的头颅先天性结构异常。共9个突变位点分别分布于3个结构域,其中尾端结构域4例,细胞活动相关的ATP酶结构域3例,茎或微管结合结构域2例。结论DYNC1H1基因异常可引起IESS,并常伴有脑发育异常和发育迟缓/智力障碍。预后不佳的原因可能是基因功能障碍和脑发育异常共同作用的结果。

Objective To report the clinical characteristics,diagnosis,and treatment process of two infants with infantile epileptic spasms syndrome(IESS) caused by DYNC1H1 mutation,and to review the relevant literature.Methods A retrospective analysis was conducted on the clinical data of two IESS patients with DYNC1H1 mutations who were treated at the First Medical Center of Chinese PLA General Hospital.Databases such as PubMed,Online Mendelian Inheritance in Man(OMIM),China National Knowledge Infrastructure(CNKI),and Wanfang Data Knowledge Service Platform were searched to obtain relevant literature,aiming to summarize the clinical characteristics of IESS patients with DYNC1H1 mutations,and to explore the relationship between treatment and phenotype-genotype.Results Two IESS patients with DYNC1H1 mutations were identified(case 1:c.874C>T,p.Arg292Trp;case 2:c.5884C>T,p.Arg1962Cys).Both patients presented with the onset of spastic seizures in infancy,which were poorly controlled with various medications.They exhibited severe developmental delay,and cranial magnetic resonance imaging in case 1 revealed pachygyria.A search of multiple databases and manual screening yielded a total of 7 English articles and 2 Chinese articles.Fifteen cases of DYNC1H1-related IESS were identified,of which 12 cases progressed to drug-resistant epilepsy and 12 cases had significant congenital structural abnormalities of the cranium.Nine different mutation sites were distributed in 3 structural domains,including 4 cases in the tail domain,3 cases in the motor with ATPase subunit domain,and 2 cases in the stalk or microtubule-binding domain.Conclusions DYNC1H1 gene variations can cause IESS,often accompanied by brain developmental abnormalities and developmental delay/intellectual disability.The poor prognosis may be attributed to the combined effects of gene dysfunction and brain developmental abnormalities.