SCN1A相关发育性癫痫性脑病46例患儿的临床表型与基因型的对应关系  

Correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy

作　　者：彭炳蔚 朱海霞 田杨 李小晶 王秀英 高媛媛 张雅妮 沈慧玲 陈文雄 Peng Bingwei;Zhu Haixia;Tian Yang;Li Xiaojing;Wang Xiuying;Gao Yuanyuan;Zhang Yani;Shen Huiling;Chen Wenxiong(Department of Neurology,Women and Children′s Medical Center affiliated to Guangzhou Medical University,Guangzhou,Guangdong 510120,China)

机构地区：[1]广州医科大学附属妇女儿童医疗中心神经内科,广州510120

出　　处：《中华医学遗传学杂志》2024年第4期426-431,共6页Chinese Journal of Medical Genetics

基　　金：2021年度"CAAE癫痫科研基金"(CX-A-2021-08)。

摘　　要：目的探讨46例SCN1A相关发育性癫痫性脑病(DEE)患儿的临床表型与基因型之间的对应关系。方法收集2018年1月至2022年6月于广州市妇女儿童医疗中心就诊的46例携带SCN1A变异的DEE患儿的临床资料。将其按照起病年龄、临床表现、神经发育情况及基因测序结果进行分组,分析SCN1A基因型与临床表型的对应关系。结果在46例患儿中,2例(4.35%)于3个月内起病,42例(91.30%)于3~9个月内起病,2例(4.35%)于10个月后起病。2例(4.35%)表现为婴儿癫痫伴游走性局灶发作(EIFMS);44例(95.7%)表现为Dravet综合征(DS),其中28例(63.6%)为局灶型(DS-F),13例(29.5%)为肌阵挛型(DS-M),1例(2.27%)为全面型(DS-G),2例(4.55%)为持续型(DS-SE)。2例EIMFS患儿均存在重度发育落后;44例DS患儿中,7例发育正常,其余均存在发育落后。基因测序共检出44处变异,其中错义变异16处,截短变异28处。EIFMS组均携带c.677C>T(p.Thr226Met)错义变异;DS组中,错义变异组和截短变异组的起病年龄存在明显差异(P<0.05),错义变异多位于D1(7/15,46.7%)与孔区(8/15,53.3%),截短变异多位于D1(12/28,42.9%);变异位于非孔区的患儿肌阵挛发作较为多见。结论DEE的临床表型多样,携带SCN1A基因的截短变异与错义变异者的起病年龄存在差异,非孔区错义变异者肌阵挛发作较为多见。Objective To explore the correlation between clinical phenotypes and genotypes among 46 children with SCN1A-related developmental epileptic encephalopathy(DEE).Methods Clinical data of 46 children with DEE and SCN1A variants identified at the Guangzhou Women and Children′s Medical Center between January 2018 and June 2022 were collected.The children were grouped based on their age of onset,clinical manifestations,neurodevelopmental status,and results of genetic testing.The correlation between SCN1A genotypes and clinical phenotypes was analyzed.Results Among the 46 patients,2 children(4.35%)had developed the symptoms before 3 months of age,42(91.30%)were between 3 to 9 months,and 2 cases(4.35%)were after 10 months.Two cases(4.35%)presented with epilepsy of infancy with migrating focal seizures(EIMFS),while 44(95.7%)had presented with Dravet syndrome(DS),including 28 cases(63.6%)with focal onset(DS-F),13 cases(29.5%)with myoclonic type(DS-M),1 case(2.27%)with generalized type(DS-G),and 2 cases(4.55%)with status epilepticus type(DS-SE).Both of the two EIMFS children had severe developmental delay,and among the DS patients,7 cases had normal development,while the remaining had developmental delay.A total of 44 variants were identified through genetic sequencing,which included 16 missense variants and 28 truncating variants.All EIMFS children had carried the c.677C>T(p.Thr226Met)missense variant.In the DS group,there was a significant difference in the age of onset between the missense variants group and the truncating variants group(P<0.05).Missense variants were more common in D1(7/15,46.7%)and pore regions(8/15,53.3%),while truncating variants were more common in D1(12/28,42.9%).Children with variants outside the pore region were more likely to develop myoclonic seizures.Conclusion The clinical phenotypes of DEE are diverse.There is a difference in the age of onset between individuals with truncating and missense variants in the SCN1A gene.Missense variants outside the pore region are associated with a higher in

关 键 词：SCN1A基因 发育性癫痫性脑病 DRAVET综合征 婴儿癫痫伴游走性局灶性发作 

分 类 号：R742.1[医药卫生—神经病学与精神病学] R747.9[医药卫生—临床医学]