GRIN2B基因变异相关儿童神经系统发育异常临床特点和基因分析  

Clinical characteristics and gene analysis of GRIN2B gene related neurological developmental disorders in children

作　　者：田小娟 王晓慧[1] 丁昌红[1] 方方[1] 代丽芳[1] 邓劼[1] 王红梅[1] Tian Xiaojuan;Wang Xiaohui;Ding Changhong;Fang Fang;Dai Lifang;Deng Jie;Wang Hongmei(Department of Neurology,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health,Beijing 100045,China)

机构地区：[1]国家儿童医学中心首都医科大学附属北京儿童医院神经内科,北京100045

出　　处：《中华儿科杂志》2022年第3期232-236,共5页Chinese Journal of Pediatrics

摘　　要：目的分析GRIN2B基因变异相关儿童神经系统发育异常的临床表型特点及基因诊断。方法回顾性分析2016年11月至2021年2月首都医科大学附属北京儿童医院神经内科确诊的GRIN2B基因变异相关神经系统发育异常11例患儿病例资料,对其临床表现、脑电图、影像学及基因特点进行总结。结果11例患儿中男6例、女5例。2例表型为发育性癫痫性脑病,癫痫发病年龄分别为3和9月龄,癫痫发作类型有痉挛发作、强直发作、强直-痉挛发作和局灶性发作,其中1例合并惊跳发作;脑电图示多灶性异常放电;2例患儿均联合应用2种以上抗惊厥药物,发作有所减少但仍未控制;均有中到重度智力、运动发育落后。9例表型为发育落后不伴癫痫发作,就诊年龄1岁至6岁4月龄,其中5例为重度发育落后,2例为中度发育落后,2例为轻度发育落后;3例行脑电图检查可见多灶性痫样放电,3例未见异常,3例未进行脑电图检查。10例患儿行头颅磁共振成像检查,6例存在非特异性异常,4例正常。11例患儿经二代测序方法检测出9个GRIN2B基因杂合变异位点,8个为错义变异,1个为无义变异,均为新生变异;其中3个变异位点为新发变异。携带错义变异者10例,其中6例重度发育落后,3例中度发育落后,1例轻度发育落后;1例无义变异携带者表型为轻度发育落后不伴癫痫。结论GRIN2B基因变异相关儿童神经系统发育异常表型多样,可从轻度智力障碍不伴癫痫到严重的癫痫性脑病。癫痫表型患儿多在婴儿期起病,以痉挛发作、局灶性发作常见,发作难以控制。携带错义变异者多存在重度发育落后。Objective To analyse the clinical and gene characteristics of GRIN2B gene related neurological developmental disorders in children.Methods The data of 11 children with GRIN2B gene related neurological developmental disorders from November 2016 to February 2021 were collected from Department of Neurology,Beijing Children′s Hospital,Capital Medical University,National Center for Children′s Health and analyzed retrospectively.The clinical features,electroencephalogram(EEG),brain imaging and gene testing results were summarized.Results Among 11 children 6 were boys and 5 were girls.Two of them were diagnosed with developmental and epileptic encephalopathy.The ages of seizures onset were 3 months and 9 months,respectively.Seizure types included epileptic spasm,tonic seizures,tonic spasm and focal seizures,and 1 patient also had startle attacks.EEG showed interictal multifocal epileptiform discharges.Both of them were added with more than 2 anti-seizure drugs,which were partially effective but could not control.They had moderate to severe mental and motor retardation.The phenotype of 9 cases was developmental delay or intellectual disability without epilepsy,age of visit 1 year to 6 year and 4 months of whom 5 cases had severe developmental delay,2 cases had moderate and 2 cases had mild delay.Multi-focal epileptiform discharges were observed in 3 cases,no abnormality was found in 3 cases,and the remaining 3 cases did not undergo EEG examination.Ten cases underwent brain magnetic resonance imaging(MRI),6 cases had nonspecific abnormalities and 4 cases were normal.Nine GRIN2B gene heterozygous variants were detected by next-generation sequencing in these 11 patients,8 cases had missense variants and 1 case had nonsense variant,all of which were de novo and 3 of which were novel.Missense variants were found in 10 patients,among them 6 cases had severe developmental delay,3 cases had moderate and 1 case had mild developmental delay,but the patient with nonsense variant showed mild developmental delay without epilepsy.

关 键 词：癫痫 GRIN2B基因 脑病 发育落后 

分 类 号：R742.1[医药卫生—神经病学与精神病学]