NEXMIF基因突变导致智力障碍合并癫痫2例并文献复习  

NEXMIF mutations in intellectual disability and epilepsy:A report of 2 cases and literature review

作　　者：陈施梦 邓小鹿[1] 熊娟[1] 陈柏谕 何芳[1] 杨丽芬[1] 羊蠡[1] 彭镜[1] 尹飞[1] CHEN Shimeng;DENG Xiaolu;XIONG Juan;CHEN Baiyu;HE Fang;YANG Lifen;YANG Li;PENG Jing;YIN Fei(Department of Pediatrics,Xiangya Hospital,Central South University,Research Center of Children Intellectual Disability of Hunan Province,Changsha 410008,China)

机构地区：[1]中南大学湘雅医院儿科,湖南省儿童智力障碍研究中心,长沙410008

出　　处：《中南大学学报（医学版）》2022年第2期265-270,共6页Journal of Central South University ：Medical Science

基　　金：湖南省重点领域研发计划(2019SK2081);湖南省自然科学基金(2021JJ40986);中南大学中央高校基本科研业务费专项资金(2019zzts347)。

摘　　要：目前已发现超过100个位于X染色体上的基因与X连锁智力障碍(X-linked intellectual disability,XLID)相关。NEXMIF基因是一个XLID致病基因,该基因突变的患者除表现为智力障碍外,还可合并癫痫、行为异常、肌张力降低等其他神经系统症状,以及其他系统的异常。中南大学湘雅医院儿科2017年3月8日至2020年6月20日收治2例NEXMIF基因突变导致智力障碍合并癫痫的患儿。病例1,女,7岁8个月,因“发育落后6年”就诊,体格检查示右眼斜视、多动、注意力不集中。智力测试显示发育商为43.6,脑电图显示异常放电,头颅影像学无明显异常。全外显子测序发现NEXMIF基因(NM_001008537)存在新发c.2189delC(p.S730Lfs*17)杂合突变。随访期间患儿出现癫痫发作,表现为全身性发作、失神发作,目前使用左乙拉西坦联合拉莫三嗪治疗中,病情暂时得到控制。病例2,男,6个月,因“发育倒退3个月,抽搐2个月”就诊。出生后有喂养困难,既往有喉软骨发育不良病史。体格检查发现追光追物差,竖头不稳,四肢肌张力减低。脑电图监测到间断高度失律及痉挛发作,先后予托吡酯、促肾上腺皮质激素(adrenocorticotrophic hormone,ACTH)治疗。全外显子测序发现NEXMIF基因存在新发c.592C>T(Q198X)突变。随访过程中加用氨己烯酸片后患儿抽搐缓解,精神运动发育无明显进步,并出现斜视。目前国外报道91例NEXMIF基因突变患者,国内报道1例,外加本研究中的2例患儿,共94例。PubMed和HGMD共收录83个NEXMIF基因突变,加上本研究发现的2个未报道的突变,共85个突变。NEXMIF基因突变患者主要表现为轻到重度智力障碍,常常合并行为异常、癫痫、肌张力低下等其他神经系统症状。男性和女性患者临床表现互有重叠,男性患者常常表现为更严重的智力障碍、语言障碍、孤独症样症状,女性患者多合并难治性癫痫。目前报道的NEXMIF基因变异大多为导致NEXMIMore than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability(XLID)to date,and NEXMIF is a pathogenic gene for XLID.In addition to intellectual disability,patients with NEXMIF gene mutation can also have other neurological symptoms,such as epilepsy,abnormal behavior,and hypotonia,as well as abnormalities of other systems.Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics,Xiangya Hospital,Central South University from March 8,2017 to June 20,2020.Patient 1,a 7 years and 8 months old girl,visited our department because of the delayed psychomotor development.Physical examination revealed strabismus(right eye),hyperactivity,and loss of concentration.Intelligence test showed a developmental quotient of 43.6.Electroencephalogram showed abnormal discharge,and cranial imaging appeared normal.Whole exome sequencing revealed a de novo heterozygous mutation,c.2189delC(p.S730Lfs*17)in the NEXMIF gene(NM_001008537).During the follow-up period,the patient developed epileptic seizures,mainly manifested as generalized and absent seizures.She took the medicine of levetiracetam and lamotrigine,and the seizures were under control.Patient 2,a 6-months old boy,visited our department due to developmental regression and seizures.He showed poor reactions to light and sound,and was not able to raise head without aid.Hypotonia was also noticed.The electroencephalogram showed intermittent hyperarrhythmia,and spasms were monitored.He was given topiramate and adrenocorticotrophic hormone(ACTH).Whole exome sequencing detected a de novo c.592C>T(Q198X)mutation in NEXMIF gene.During the follow-up period,the seizures were reduced with vigabatrin.He had no obvious progress in the psychomotor development,and presented strabismus.There were 91 cases reported abroad,1 case reported in China,and 2 patients were included in this study.A total of 85 variants in NEXMIF gene were found,involving 83 variants reported in

关 键 词：NEXMIF基因 智力障碍 癫痫 婴儿痉挛 

分 类 号：R725.9[医药卫生—儿科]