[1]董晓立 李花 张佩琪等.SCN2A基因突变所致癫痫的遗传和表型特点[J].卒中与神经疾病杂志,2022,29(03):274-280.[doi:10.3969/j.issn.1007-0478.2022.03.016]
　Dong Xiaoli,Li Hua,Zhang Peiqi,et al.Genotypic and phenotypic characteristics of SCN2A-associated epilepsy[J].Stroke and Nervous Diseases,2022,29(03):274-280.[doi:10.3969/j.issn.1007-0478.2022.03.016]
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SCN2A基因突变所致癫痫的遗传和表型特点()
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《卒中与神经疾病》杂志[ISSN:1007-0478/CN:42-1402/R]

卷:
第29卷
期数:
2022年03期
页码:
274-280
栏目:
癫 痫
出版日期:
2022-06-25

文章信息/Info

Title:
Genotypic and phenotypic characteristics of SCN2A-associated epilepsy
文章编号:
1007-0478(2022)03-0274-07
作者:
董晓立 李花 张佩琪等
510510 暨南大学附属广东三九脑科医院癫痫中心
Author(s):
Dong Xiaoli;  Li Hua;  Zhang Peiqi;  et al.
Department of Epilepsy Center, Guangdong Sanjiu Brain Hospital Affiliated to Jinan University, Guangzhou Guangdong 510510
关键词:
SCN2A基因 癫痫 电压门控钠离子通道Ⅱ型 治疗
Keywords:
SCN2A gene Epilepsy Nav1.2 Therapy
分类号:
R742.1
DOI:
10.3969/j.issn.1007-0478.2022.03.016
文献标志码:
A
摘要:
目的 探讨SCN2A(Sodium channel,voltage-gated,type II,alpha)基因突变所致癫痫的遗传及表型特点。方法 收集广东三九脑科医院癫痫中心2016年8至2021年4月收治的癫痫患儿,应用全外显捕获高通量测序技术发现SCN2A基因突变者,回顾性总结分析患儿临床及遗传资料。结果 共收集14例SCN2A基因突变阳性患儿,其中男7例,女7例,起病年龄1 d～6岁,其中3月龄内起病者8例(57.1%),3月龄后起病者6例(42.9%)。共发现13种突变,均为杂合错义突变。2例携带相同母源SCN2A突变,均为良性家族性癫痫; 3例携带父源突变,其中2例发作缓解(66.7%); 9例为新发突变,4例发作缓解(44.4%)。14例SCN2A突变癫痫患儿存在多种发作类型,以局灶性发作(64.3%)、痉挛发作(42.9%)、强直发作(35.7%)为主,其他发作类型较为少见; 8例患者有丛集性发作(57.1%)。14例患儿脑电图可见多种放电模式,以局灶性放电8例(57.1%)、弥漫性放电6例(42.9%)、多灶性放电5例(35.7%)多见。头部磁共振成像(Magnetic resonance imaging,MRI)以大脑发育不良(白质发育不良、白质变性、脑室发育不良、胼胝体发育不良、弥漫性脑萎缩)多见(42.9%)。除2例良性家族性癫痫患儿外,12例发育性/癫痫性脑病患儿,2例大田原综合征,3例韦斯特综合征,3例发育性脑病,3例发育性癫痫性脑病,1例婴儿游走性部分性发作,发育均呈中重度发育迟缓; 其中3月龄前起病者(早发SCN2A相关癫痫)10例,5例发作缓解; 3月龄后起病者(晚发SCN2A相关癫痫)2例,1例发作缓解。14例患儿抗癫痫治疗方案有较大个体差异,2例良性家族性癫痫对德巴金效果佳; 12例发育性/癫痫性脑病患儿中10例早发SCN2A相关癫痫患儿有6例尝试奥卡西平,4例有效(66.7%); 3例晚发患儿,1例应用且无效,但无加重发作。结论 SCN2A基因突变以错义突变为主,新发错义突变较遗传性突变预后差。SCN2A突变导致电压门控钠离子通道(Voltage-gated Na channel,VGNC或Nav)的Ⅱ型Nav1.2两种功能改变:获得功能和丧失功能,早发型(起病年龄<3月龄)Nav1.2以获得功能为主,对钠离子通道阻滞剂(Sodium channel blockers,SCBs)效果佳; 晚发型(起病年龄≥3月龄)Nav1.2以丧失功能为主,对SCBs效果差,甚至可能加重发作。SCBs首选适量苯妥英钠治疗。其他治疗如奥卡西平、生酮饮食、促肾上腺皮质激素(Adrenocorticotropic horme,ACTH)、氨己烯酸亦可尝试,且应个体化调整治疗方案。
Abstract:
Objective To explore the genotypic and phenotypic characteristics of epilepsy caused by sodium voltage-gated channel alpha subunit 2(SCN2A)gene mutation.Methods The children with epilepsy treated in the epilepsy center of Guangdong Sanjiu brain hospital from August 2016 to April 2021 were collected. The SCN2A gene mutations were found by using full exon capture high-throughput sequencing technology. The clinical and genetic data of the children were retrospectively summarized and analyzed.Results A total of 14 children with SCN2A gene mutation were collected, including 7 males and 7 females. The onset age fluctuated from 1 day to 6 years after birth, including 8 cases(57.1%)within 3 months and 6 cases(42.9%)after 3 months. A total of 13 mutations were found, all of which were heterozygous missense mutation. Two patients with the same maternal SCN2A mutation were benign familial epilepsy; 3 cases carried paternal mutation, 2 cases with seizure remission(66.7%); 9 cases hadde novo mutations, 4 cases with seizure remission(44.4%). There were several seizure types in 14 children withSCN2A mutation associated epilepsy, mainly focal seizure(64.3%), spastic seizure(42.9%), tonic seizure(35.7%), and other seizure types were rare; Eight patients had cluster seizures(57.1%). The EEG of 14 children showed multiple discharge patterns, most of which were focal discharge(8 cases,57.1%), diffuse discharge( 6 cases,42.9%), multifocal discharge( 5 cases,35.7%). Brain dysplasia including white matter dysplasia, white matter degeneration, ventricular dysplasia, corpus callosum dysplasia and diffuse brain atrophy was more common in head MRI(42.9%). Except for 2 cases of benign familial epilepsy, 12 cases of developmental and epileptic encephalopathy, 2 cases of Otahara syndrome, 3 cases of West syndrome, 3 cases of developmental encephalopathy, 3 cases of developmental epileptic encephalopathy, 1 case of infantile migratory partial seizure, and all exhibited with moderate and severe delayed development. Among them, there were 10 patients(early-onset SCN2A related epilepsy)with first onset before 3 months old, and 5 cases were relieved, There were 2 cases of late onset SCN2A related epilepsy with first onset after 3 months, and 1 case remitted. There were significant individual differences in antiepileptic treatment in 14 children. 2 cases of benign familial epilepsy had a good response to VPA. Among the 12 children with developmental and epileptic encephalopathy, 10 children were early-onset SCN2A related epilepsy, 6 tried OXC, and 4 were effective(66.7%). In 3 cases of late onset children, 1 case was treated ineffectively without aggravation.Conclusion Most of SCN2A gene mutations were missense, and the prognosis of de novo missense mutation was worse than that of genetic mutation. SCN2A mutations resulted in two types of changes in NaV1.2 function: gain of function and loss of function. For patients with early onset epilepsy(onset age < 3 months), the mutation mainly led to NaV1.2 gain of function and patients had a good response to sodium channel blockers(SCBs). Otherwise, late onset epilepsy(onset age ≥ 3 months)exhibited loss of NaV1.2 function. Patients had a poor response to SCBs, and SCBs might even aggravate the seizure. Therapy should be initiated with appropriate amount of phenytoin sodium. Other drugs, such as oxcarbazepine, ketogenic diet, adrenocorticotropic hormone(ACTH)and aminohexenoic acid, could also be tried, and the treatment scheme should be adjusted individually.

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备注/Memo

备注/Memo:
基金项目:广州市科技计划项目(202102080427)
更新日期/Last Update: 1900-01-01