KCNC1基因突变导致的进行性肌阵挛癫痫3例及文献复习  

Three cases of progressive myoclonic epilepsy caused by KCNC1 gene mutations and literature review

作　　者：张静[1] 张月华[1] 陈娇阳 杨莹 曾琦[1] 杨小玲[1] 吴希如[1] Zhang Jing;Zhang Yuehua;Chen Jiaoyang;Yang Ying;Zeng Qi;Yang Xiaoling;Wu Xiru(Department of Pediatrics,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]北京大学第一医院儿科,100034

出　　处：《中华实用儿科临床杂志》2019年第24期1876-1881,共6页Chinese Journal of Applied Clinical Pediatrics

摘　　要：目的总结3例KCNC1基因突变导致进行性肌阵挛癫痫(PME)患儿的临床表型及基因型特点,并进行文献复习。方法对2016年10月至2019年1月就诊于北京大学第一医院儿科的3例KCNC1基因突变患儿的临床特点和基因型特点进行分析,并对国际上已报道的25例KCNC1基因突变患者进行总结分析。结果本研究中的3例患儿均为KCNC1基因新生变异,2例为c.959G>A(p.Arg320His)变异,1例为c.1262C>T(p.Ala421Val)变异。3例患儿临床特点均符合PME,癫痫发病年龄分别为3月龄、10岁和11岁;3例患儿均有肌阵挛发作,1例有全面强直阵挛发作(GTCS),2例有局灶性发作;3例患儿均有智力和/或运动发育落后。3例患儿脑电图均显示广泛性棘慢波或多棘慢波,2例有局灶性放电。头颅影像学均无异常。末次随访年龄分别为3岁、13岁和12岁。截至2019年3月,国际上已报道25例KCNC1基因突变患者,加上本研究3例共28例患者,其中25例临床诊断符合PME,基因检测结果为位于跨膜区的p.Arg320His变异24例;位于跨膜区的p.Ala421Val变异1例;另3例患者仅有智力运动发育落后,无癫痫发作,该3例患者均为位于胞内区的p.Arg339X变异。28例患者中,获得头颅影像学资料16例,其中小脑萎缩12例,正常4例。28例患者中,智力发育落后18例,运动发育落后或倒退27例,其中9例丧失独立行走能力。10例患者报道时超过30岁,仅1例患者在63岁因肺炎及呼吸衰竭死亡。结论KCNC1基因突变主要导致PME表型,少数可仅表现为智力运动发育落后;p.Arg320His为KCNC1基因最常见的变异类型。不同结构区域的变异导致的临床表型存在差异,位于跨膜区的变异可导致更严重的临床表型。本研究中3例KCNC1基因突变患儿为国内首次报道。Objective To summarize the clinical phenotype and genotype features of 3 children with progre-ssive myoclonic epilepsy(PME)caused by KCNC1 gene mutations,and to review the related literatures.Methods The phenotype and genotype of 3 children with KCNC1 mutations in the Department of Pediatrics,Peking University First Hospital from October 2016 to January 2019 were analyzed.The 25 patients with KCNC1 mutations which had been reported internationally were also collected and analyzed.Results Three children in this study were identified with KCNC1 de novo mutations,in which 2 children were identified with c.959G>A(p.Arg320His)mutation,and 1 child with c.1262C>T(p.Ala421Val)mutation.The clinical features of 3 children were consistent with PME,and the seizure onset ages were 3 months,10 years and 11 years,respectively.Three children all had myoclonic seizures,among whom 1 child had generalized tonic-clonic seizure and 2 children had focal seizures.Three children all had intellectual and/or motor development delay.The electroencephalograph showed generalized spike and waves or polyspike and waves in 3 children,and focal discharge in 2 children.The brain imaging of 3 children was normal.The last follow-up ages were 3 years old,13 years old and 12 years old,respectively.Until March 2019,there were 25 cases with KCNC1 gene mutations reported internationally.Including 3 patients in this study,there were 28 patients in total,of which 25 patients were diagnosed with PME.In these 25 patients,24 patients were identified with p.Arg320His variant in the transmembrane area,1 patient was identified with p.Ala421Val variant in the transmembrane area.The remaining 3 patients were only found with psychomotor developmental delay without seizures,and they were identified with p.Arg339X variant in the intracellular area.In the 28 patients,16 cases received cranial imaging data,in which 12 patients had ce-rebellar atrophy and 4 cases were normal.Of the 28 patients,18 cases were mentally retarded,27 cases were development retardation or ret

关 键 词：KCNC1基因 肌阵挛癫痫 进行性 

分 类 号：R742[医药卫生—神经病学与精神病学]