KCNQ2基因变异致新生儿癫痫15例临床和基因分析
Clinical and genetic characteristics of neonatal epilepsy caused by KCNQ2 mutations:15 cases experience
李雨聪 1杨子欣 1郑侠1
作者信息
- 1. 国家儿童医学中心首都医科大学附属北京儿童医院新生儿中心,北京 100045
- 折叠
摘要
目的 探讨KCNQ2基因变异导致新生儿癫痫患儿的临床和基因变异特点.方法 对北京儿童医院新生儿中心2017年1月至2021年12月收治的因KCNQ2基因变异导致的新生儿癫痫患儿进行回顾性研究,总结其临床特征和基因变异特点.结果 共纳入15例,发病日龄0～24 d.发作类型为强直发作7例(7/15)、癫痫性痉挛发作4例(4/15)、阵挛发作2例(2/15)、自动症2例(2/15);脑电图表现发作间期局灶或多灶性放电6例(6/15)、暴发-抑制4例(4/15)、高度失律3例(3/15)、低电压2例(2/15).共检测出15种不同的KCNQ2基因杂合变异,其中错义变异13例(13/15)、移码变异2例(2/15),变异来源为新发变异14例、母源性1例.临床表型为发育性癫痫性脑病9例(9/15)、自限性新生儿癫痫5例(5/15)、自限性家族性新生儿-婴儿癫痫1例(1/15).使用的抗癫痫药物包括苯巴比妥13例、左乙拉西坦6例、奥卡西平5例、托吡酯5例.加用奥卡西平或托吡酯时间为1.0(0.3～3.0)月龄,发作减少或控制时间为2.5(1.0～12.0)月龄,停药时间为6.0(6.0～12.0)月龄.平均随访时间25.5(11.0～48.0)个月,发作控制或减少12例(12/15),其中6例自限性家族性新生儿-婴儿癫痫及自限性新生儿癫痫发作均控制,死亡3例(3/15).结论 KCNQ2基因变异导致的新生儿癫痫,新发变异较遗传性变异更常见,临床表型多为发育性癫痫性脑病,如单用苯巴比妥控制发作效果不佳,可尽早加用奥卡西平或托吡酯.
Abstract
Objective To study the clinical characteristics and genetic profiles of neonatal epilepsy caused by KCNQ2 gene mutations.Methods From Jan 2017 to Dec 2021,neonates with epilepsy caused by KCNQ2 gene mutations treated in our hospital were retrospectively reviewed.The clinical features,genetic profiles,treatments and outcomes were summarized.Results A total of 15 patients were enrolled,with the onset of epilepsy during 0～24 d of age.The types of seizures included 7 cases(7/15)of tonic seizures,4 cases(4/15)of epileptic spasms,2 cases(2/15)of clonic seizures and automatic seizure,respectively.Electroencephalogram showed focal or multifocal interictal discharges in 6 cases(6/15),hypsarrhythmia in 3 cases(3/15),burst-suppression in 4 cases(4/15)and low voltage in 2 cases(2/15).15 heterozygous KCNQ2 gene mutations were identified,including 13(13/15)missense mutations and 2(2/15)frameshift mutations.14 mutations were de novo and 1 from the mother.The clinical phenotypes included developmental epileptic encephalopathy in 9 cases(9/15),self-limited neonatal epilepsy in 5 cases(5/15)and benign familial neonatal epilepsy in 1 case(1/15).The antiepileptic drugs included phenobarbital in 13 cases,levetiracetam in 6 cases,oxcarbazepine and topiramate in 5 cases,respectively.Oxcarbazepine or topiramate was added on 1.0(0.3-3.0)months of age.Reduced or controlled seizure was achieved on 2.5(1.0-12.0)months and the antiepileptic drugs were stopped at 6.0(6.0-12.0)months.The mean follow-up time was 25.5(11.0-48.0)months and seizures were reduced/controlled in 12 cases(12/15),including all 6 cases of self-limited neonatal seizures and benign familial neonatal epilepsy.3 cases(3/15)were dead.Conclusions Neonatal epilepsy caused by KCNQ2 gene mutations,with de novo variants more common than hereditary,tends to have a clinical phenotype of developmental epileptic encephalopathy and may be treated with early add-on of oxcarbazepine or topiramate if phenobarbital alone is ineffective.
关键词
新生儿/癫痫/KCNQ2基因Key words
Neonates/Epilepsy/KCNQ2gene引用本文复制引用
基金项目
学生科研创新项目(XSKY2023340)
出版年
2024
NETL
NSTL
万方数据