| 国志,郑芳,赵鹏军.癫痫伴热性惊厥病儿 SCN1A、SCN2A基因突变特点及表型分析[J].安徽医药,2025,29(2):319-324. |
| 癫痫伴热性惊厥病儿 SCN1A、SCN2A基因突变特点及表型分析 |
| Analysis of characteristics and phenotypes of SCN1A and SCN2A gene mutations in children with epilepsy with febrile seizures |
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| DOI：10.3969/j.issn.1009-6469.2025.02.022 |
| 中文关键词: 癫痫 惊厥，发热性 SCN1A基因 SCN2A基因 基因突变 |
| 英文关键词: Epilepsy Seizures,febrile SCN1A gene SCN2A gene Gene mutation |
| 基金项目:上海市进一步加快中医药事业发展三年行动计划立项课题［ZY(2018-2020)-FWTX-3015］ |
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| 中文摘要: |
| 目的探究并分析 SCN1A、SCN2A基因突变相关癫痫伴热性惊厥病儿的表型特征及基因型。方法回顾性选取 2020年 6月至 2022年 1月上海市第六人民医院(临港院区)儿科长期随访的 56例接受基因筛查的癫痫伴热性惊厥病儿临床资料，抽取所有病儿及其父母静脉全血进行基因测序寻找发现可疑致病性突变， Sanger测序验证基因突变来源，观察 SCN1A、SCN2A基因突变病儿临床特征、临床表型、治疗方案、预后以及基因突变情况。结果 56例病儿中基因检测结果为阴性者 42例，阳性者 14例，其中单纯 SCN1A基因突变 7例，单纯 SCN2A基因突变 6例， SCN1A、SCN2A均突变 1例。 14例基因突变病儿男性 6例，女性 8例，发作年龄由 2d至 2岁 7个月，治疗年龄由 1个月至 3岁；临床特点为智力发育落后 11例(轻度 7例，中度 4例)，轻度神经发育落后 2例，轻度语言发育落后 1例；临床表型为热性惊厥附加症 9例， Dravet综合征 3例，婴儿痉挛征 1例，早发癫痫性脑病 1例；癫痫发作类型为阵挛 6例，强直 4例，失张力 2例，强直 -阵挛 1例，失神 1例；发作频率由每日 8~12次至每月 5~8次，持续时间由数十秒至 3 min，治疗方案以丙戊酸、左乙拉西坦、托吡酯、妥泰、奥卡西平、硝西泮、强的松等单独或组合治疗； 8例病儿经治疗后发作控制， 6例病儿发作减少。 14例基因突变病儿有 7例为 SCN1A突变，主要突变点位为 Chr2，5例为错义突变， 1例为移码突变， 1例为剪切位点突变； 5例为常染色体显性遗传， 2例为 X染色体遗传； 4例来源于母亲， 2例来源于父亲， 1例来源于新生。 6例为 SCN2A突变，主要突变点位为 Chr2，4例为错义突变， 1例为移码突变， 1例为非编码区突变；均为常染色体显性遗传； 2例来源于母亲， 1例来源于父亲， 3例来源于新生。 1例为 SCN1A、SCN2A双突变，突变类型为错义突变。结论 SCN1A、 SCN2A基因突变均以错义突变为主，主要由新生变异和遗传变异造成，临床多表现为热性惊厥附加症， SCN1A、SCN2A基因可作为临床早期防治癫痫伴热性惊厥的有效靶点。 |
| 英文摘要: |
| Objective To explore and analyze the phenotypic characteristics and genotypes of children with epilepsy with febrile sei-zures associated with SCN1A and SCN2A gene mutations.Methods The clinical data of 56 children with epilepsy and febrile seizureswho underwent genetic screening and were followed up in department of pediatrics of the Shanghai Sixth People's Hospital (LingangHospital District) were retrospectively selected from June 2020 to January 2022. Venous whole blood of all children and their parentswere collected for gene sequencing to find suspected pathogenic mutations. Sanger sequencing was used to verify the sources of genemutations.The clinical characteristics, clinical phenotyping, treatment regimen method, prognosis and gene mutations were comparedbetween children with SCN1A and SCN2A gene mutations.Results Among the 56 children, 42 cases were negative and 14 cases werepositive by gene test, including 7 cases of simple SCN1A gene mutation, 6 cases of simple SCN2A gene mutation and 1 case of bothSCN1A and SCN2A mutations. Among the 14 cases with gene mutations, 6 cases were males and 8 cases were females, with the age ofonset from 2 days to 2 years and 7 months and the treatment age from 1 month to 3 years old. The clinical features were shown as men-tal retardation in 11 cases (mild in 7 cases, moderate in 4 cases), mild neurodevelopmental retardation in 2 cases and mild language re-tardation in 1 case. Clinical phenotypes were manifested as febrile seizure plus in 9 cases, Dravet syndrome in 3 cases, infantile spasm in 1 case and early-onset epileptic encephalopathy in 1 case. The seizure types were expressed as 6 cases of clonic seizure, 4 cases oftonic seizure, 2 cases of tension loss, 1 case of tonic-clonic seizure and 1 case of loss of consciousness. The seizure frequency ranged from 8-12 times a day to 5-8 times a month, and the duration from tens of seconds to 2 to 3 minutes and the treatment regimen was withvalproic acid, levetiracetam, topiramate, topamax, oxcarbazepine, nitrazepam and prednisone alone or in combination. The seizureswere controlled in 8 cases and reduced in 6 cases after treatment. Among the 14 children with gene mutations, there were 7 cases ofSCN1A mutation with the main mutation site of Chr2, including 5 cases of missense mutation, 1 case of frameshift mutation and 1 caseof shear site mutation; there were 5 cases of autosomal dominant inheritance and 2 cases of X chromosome inheritance; there were 4cases from the mother, 2 cases from the father and 1 case from the newborn. 6 cases were with SCN2A mutation with the main mutationsite of Chr2, including 4 cases of missense mutation, 1 case of frameshift mutation and 1 case of non-coding region mutation; all caseswere autosomal dominant inheritance; there were 2 cases from the mother, 1 case from the father and 3 cases from the newborn. 1 casewas with SCN1A and SCN2A mutations, with the mutation type of missense mutation.Conclusions SCN1A and SCN2A gene muta-tions are mainly missense mutations, which are mainly caused by de novo mutations and genetic mutations, with clinical manifestationsas mostly febrile seizure plus. SCN1A and SCN2A genes can be used as effective targets for early clinical prevention and treatment ofepilepsy with febrile seizures. |
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