KCNMA1基因变异相关儿童神经系统疾病表型谱研究  

Phenotypic spectrum of nervous system diseases in children associated with KCNMA1 gene mutations

作　　者：刘昌昊 杨小玲[1] 程苗苗 王婷 谭全桢 杨莹 刘文玮 张月华[1] LIU Changhao;YANG Xiaoling;CHENG Miaomiao;WANG Ting;TAN Quanzhen;YANG Ying;LIU Wenwei;ZHANG Yuehua(Pediatric Medical Center,Peking University First Hospital,Beijing 102699,China)

机构地区：[1]北京大学第一医院儿童医学中心,北京102699

出　　处：《精准医学杂志》2024年第6期495-499,共5页Journal of Precision Medicine

基　　金：国家重点研发计划项目(2023YFC2706301)。

摘　　要：目的总结KCNMA1基因变异患儿的临床表型和基因变异特点。方法回顾性分析2013年3月—2023年5月在北京大学第一医院儿童医学中心就诊的10例KCNMA1基因杂合变异患儿的临床资料,总结并分析其临床表现及颅脑影像学、脑电图特点。结果10例KCNMA1变异患儿中,男8例,女2例。共发现9个不同的KCNMA1变异位点,其中错义变异5个,移码变异3个,剪切位点变异1个。7个变异位点为新发变异,2个变异位点为遗传性变异。10例KCNMA1变异患儿中,6例仅表现为癫痫发作,3例表现为癫痫发作合并阵发性运动障碍,1例仅表现为阵发性运动障碍。9例有癫痫发作的患儿起病年龄为3日龄~1岁8月龄(中位起病年龄为8月龄),癫痫发作类型包括局灶性发作6例,癫痫性痉挛4例,肌阵挛发作2例,不典型失神发作2例,全面强直阵挛发作2例,肌阵挛失张力发作1例,失张力发作1例,5例患儿有多种发作类型。符合癫痫综合征诊断的患儿中诊断为婴儿癫痫性痉挛综合征1例,肌阵挛失张力癫痫1例。4例运动障碍患儿起病年龄为15日龄~1岁6月龄,运动障碍主要表现为阵发性非运动诱发的肌张力障碍,其中1例阵发性运动障碍合并眼球运动异常。10例KCNMA1变异患儿中,4例有颅脑MRI异常,其中脑室增宽3例,蛛网膜下腔增宽2例,胼胝体发育不良2例,脑白质髓鞘化落后1例。脑电图背景活动减慢5例;10例发作间期均监测到癫痫样放电,表现为局灶性放电、多灶性放电或广泛性放电,其中4例可见高峰失律,1例存在睡眠中癫痫性电持续状态;4例监测到癫痫发作,其中癫痫性痉挛3例,不典型失神发作1例。10例患儿均有发育落后。结论KCNMA1基因变异相关神经系统表型主要包括癫痫、阵发性非运动诱发的运动障碍和发育落后。癫痫多在2岁以内起病,具有多种发作类型,以局灶性发作常见。阵发性运动障碍主要表现为阵发性肌张力障碍。Objective To summarize the clinical phenotypes and genetic mutations of children with KCNMA1 gene mutations.Methods A retrospective analysis was performed for the clinical data of ten children with heterozygous KCNMA1 gene mutations who attended Pediatric Medical Center of Peking University First Hospital from March 2013 to May 2023,and their cli-nical manifestations,cranial radiological features,and electroencephalogram(EEG)features were summarized.Results Among the ten children with KCNMA1 mutations,there were eight boys and two girls.Nine different KCNMA1 gene mutations were identified,including five missense mutations,three frame-shifting mutations,and one splice site mutation,among which there were seven de novo mutations and two inheritable mutations.Among the ten children with KCNMA1 mutation,six presented with seizures alone,three presented with seizures and paroxysmal movement disorders,and one presented with paroxysmal movement disorders alone.For the nine children with seizures,the age of onset ranged from 3 days to 1 year and 8 months,with a median age of onset of 8 months,and the types of seizures included focal seizures(six children),epileptic spasm(four children),myoclonic seizures(two children),atypical absence seizures(two children),generalized tonic-clonic seizures(two children),myoclonic-ato-nic seizures(one child),and atonic seizures(one child),with multiple types of seizures in five children.For the children who met the diagnostic criteria for epilepsy syndrome,one child was diagnosed with infantile epileptic spasms,and one was diagnosed with myoclonic-atonic epilepsy.For the four children with movement disorders,the age of onset ranged from 15 days to 1 year and 6 months,and movement disorders mainly manifested as paroxysmal non-kinesigenic dystonia,with paroxysmal movement disorders comorbid with abnormal eye movement in one child.Among the ten children with KCNMA1 mutation,there were four children with abnormal cranial MRI findings,including ventriculomegaly(three children),subarachnoid sp

关 键 词：KCNMA1 大电导钙激活钾通道α亚基 突变 癫痫 运动障碍 发育障碍 遗传关联研究 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R394[医药卫生—临床医学]