KCNQ2 基因变异相关癫痫新生儿17例病例系列报告  

A series of 17 cases of neonatal epilepsy associated with KCNQ2 gene variation

作　　者：石权 方秀英[1] 王英杰[2] 陈淑媛[1] 田艺丽[1] 郑铎[1] 毛健[2] SHI Quan;FANG Xiuying;WANG Yingjie;CHEN Shuyuan;TIAN Yili;ZHENG Duo;MAO Jian(Shengjing Hospital of China Medical University,Department of Neurology,Shenyang 110004,China;Shengjing Hospital of China Medical University,Department of Neonatology,Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院神经功能科,沈阳110004 [2]中国医科大学附属盛京医院新生儿内科,沈阳110004

出　　处：《中国循证儿科杂志》2025年第2期117-123,I0013-I0024,共19页Chinese Journal of Evidence Based Pediatrics

摘　　要：背景KCNQ2基因变异可导致不同严重程度的新生儿癫痫表型,不同表型的脑电图特点不同,且脑电严重程度与预后相关,目前对于KCNQ2基因变异的新生儿期脑电图报道较少。目的探讨KCNQ2基因变异导致新生儿癫痫发作的早期脑电图特征、基因型与临床表型之间的关系。设计病例系列报告。方法回顾性分析中国医科大学附属盛京医院新生儿科2017年1月1日至2024年12月31日收治的KCNQ2基因变异导致的新生儿癫痫患儿的临床资料、基因型及新生儿期脑电图特征。主要结局指标基因型、脑电图表现。结果17例KCNQ2基因变异相关癫痫新生儿纳入本文分析。依据生长发育里程碑和惊厥发作对药物反应性分为自限性(家族性)新生儿癫痫(SeLNE)组和发育性癫痫性脑病(DEE)组。SeLNE组10例,基因突变来源为家系遗传7例,新发突变3例;突变类型为移码突变4例,无义突变2例,错义突变3例,剪接突变1例;氨基端改变位置除1例来源于S6,余位于胞内N端及C端;早期脑电图睡眠周期及生理波均存在或早期恢复正常,发作期多为序贯性发作,最初多以不对称强直症状起始,但序贯症状繁多,阵挛症状突出,多数发作后期呼吸暂停。DEE组7例,基因突变均为新发突变,突变类型除1例为整码突变外,余均为错义突变,氨基端改变位置位于S2、S4、S4-S5、S5、S6、P环区和胞内C端各1例。早期EEG背景多为暴发-抑制或多灶性放电伴随机性电压衰减,睡眠周期及生理波出现较晚或在新生儿期始终未出现,aEEG上边界始终呈高电压模式,发作期表现以不对称强直症状最为突出,并且有时在一次发作过程中出现强直方向的“调转”。结论SeLNE组和DEE组基因型、早期脑电图表现不同,结合早期脑电图的变化特征可进一步评估预后。Background Mutations in the KCNQ2 gene can result in neonatal epilepsy phenotypes of varying severity.These different phenotypes exhibit distinct EEG characteristics,and the severity of EEG abnormalities is correlated with prognosis.Presently,there is limited literature on neonatal EEG findings associated with KCNQ2 gene mutations.Objective To explore the relationship between early EEG characteristics,genotype and clinical phenotype of neonatal epileptic seizure caused by KCNQ2 gene variation.Design Case series report.Methods From Jan 1,2017 to Dec 31,2024,neonates with epilepsy caused by KCNQ2 gene mutations treated in Department of Neonatology,Shengjing Hospital of China Medical University were retrospectively reviewed.The clinical features,gene profiles and EEG characteristics were summarized.Main outcome measures genotype and EEG.Results 17 neonates with epilepsy related to KCNQ2 gene variation were included in this study.Patients were divided into two groups according to seizure control and follow-up.In the SeLNE group of 10 cases,gene mutations originated from family(7/10),denovo(3/10).The types of mutations were frame shift mutation(4/10),nonsense mutation(2/10),missense mutation(3/10),splicing mutation(1/10,case 8).The mutation sites in this group were majority located within the N and C terminal regions,One exception was case 7 which located within S6 segments.In SeLNE group,EEG sleep cycles and physiological waves were present or returned to normal at an early stage.Most of the seizures were characterized by asymmetric tonic feature at onset,then may progress in a sequential pattern with numerous symptoms but the clonus symptoms were prominent,and most of them were apnea at the later stage.There were 7 cases in the DEE group,all of which were denovo.Except for the whole code mutation in case 12,all of the mutations were missense mutations.The mutation sites in this group were S2 segments(1/7),S4 segments(1/7),S4-S5 segments(1/7),S5 segments(1/7),S6 segments(1/7),ion pore(1/7)and C-terminal region(1/7).T

关 键 词：KCNQ2基因 新生儿 视频脑电图 惊厥发作 

分 类 号：R742.1[医药卫生—神经病学与精神病学]