CSNK2B基因变异相关癫痫患儿的基因变异及临床表型特点

Genetic variations and clinical phenotypic characteristics of epilepsy associated with CSNK2B gene mutations

目的分析CSNK2B基因变异相关癫痫患儿的基因变异及临床表型特点。方法回顾性病例系列总结。收集2016年2月至2023年10月郑州大学第三附属医院及北京大学第一医院诊治的15例CSNK2B基因变异相关癫痫患儿的病例资料, 对其临床表现、基因型及脑电图特点等进行总结。结果 15例患儿中男8例, 女7例;14例为CSNK2B基因新生变异, 1例为遗传性变异, 其中错义变异5例, 剪接位点变异4例, 移码变异3例, 无义变异3例。10例变异位点尚未见报道(c.326G>A/p.Cys109Tyr、c.485A>G/p.His162Arg、c.368-1G>A、c.464A>C/p.Asp155Ala、c.301T>G/p.Tyr101Asp、c.342T>A/p.Cys114*、c.198del/p.Asn67Thrfs*5、c.292-10T>G、c.573-574del/p.Lys191Asnfs*54、c.11C>G/p.Ser4*)。癫痫发作起病年龄为14 d至6岁, 其中13例于2岁前起病。发作类型包括局灶性发作9例, 全面性强直阵挛发作(GTCS)5例, 肌阵挛发作1例, 失张力发作1例, 不典型失神发作1例, 癫痫性痉挛1例, 其中3例患儿有多种发作类型, 4例有丛集性发作特点。15例患儿脑电图显示, 1例背景活动慢;13例发作间期有癫痫样放电, 其中广泛性放电6例, 多灶性放电3例, 局灶性放电5例, 2例脑电图正常。10例患儿头颅磁共振成像正常。末次随访年龄1岁1个月龄至13岁10个月, 12例患儿应用1~2种抗癫痫发作药物控制发作, 2例应用多种抗癫痫发作药物仍有发作, 1例未应用抗癫痫发作药物的患儿已1年3个月无发作。5例(5/7)应用奥卡西平有效, 6例(6/8)应用丙戊酸钠有效, 3例(3/9)应用左乙拉西坦治疗有效。结论 CSNK2B基因变异主要为新发变异, 该基因变异所致癫痫发作多在2岁前起病, 癫痫发作类型主要为GTCS及局灶性发作, 多数患儿发作容易控制, 奥卡西平、丙戊酸钠及左乙拉西坦是常用有效药物。

Objective To analyze the genetic variations and clinical phenotypic characteristics of epilepsy associated with CSNK2B gene mutations.Methods A case series summary study.Clinical data of 15 epileptic children with CSNK2B gene mutations diagnosed and treated at the Third Affiliated Hospital of Zhengzhou University and the Peking University First Hospital from February 2016 to October 2023 were retrospectively analyzed.The clinical manifestations,genotypes,and electroencephalography(EEG)results were summarized.Results Among the 15 children(8 boys and 7 girls),14 cases had de novo mutations in the CSNK2B gene,and 1 case had hereditary variations.There were 5 missense variants,4 splice-site variants,3 frameshift variants,and 3 nonsense variants.Ten mutation sites had not been previously reported(c.326G>A/p.Cys109Tyr,c.485A>G/p.His162Arg,c.368-1G>A,c.464A>C/p.Asp155Ala,c.301T>G/p.Tyr101Asp,c.342T>A/p.Cys114*,c.198del/p.Asn67Thrfs*5,c.292-10T>G,c.573-574del/p.Lys191Asnfs*54,and c.11C>G/p.Ser4*).The age of onset of seizures ranged from 14 days to 6 years,with 13 cases starting within 2 years old.The types of seizures included focal seizures in 9 cases,generalized tonic-clonic seizure(GTCS)in 5 cases,myoclonic seizures in 1 case,atonic seizures in 1 case,atypical absence seizures in 1 case,and epileptic seizures in 1 case.Three cases had multiple seizures,and 4 cases had cluster seizures.The EEG showed slow background activity in 1 case.Epileptiform discharges were observed in 13 cases during the interictal phase,including generalized discharges in 6 cases,multifocal discharges in 3 cases,and focal discharges in 5 cases.Two cases had normal EEG findings.Brain magnetic resonance imaging results were normal in 10 cases.The age of the last follow-up ranged from 1 year and 1 month to 13 years and 10 months.Seizures were controlled in 12 cases treated with 1 or 2 antiepileptic drugs,while seizures persisted in 2 cases treated with multiple antiepileptic drugs,and 1 case suffered no seizures for 1 year and 3 months,without antiepileptic drug treatment.Oxcarbazepine was effective in 5 cases(5/7),Valproate sodium was effective in 6 cases(6/8),and Levetiracetam was effective in 3 cases(3/9).Conclusions CSNK2B gene mutations are mainly de novo mutations,and epilepsy triggered by them typically starts within 2 years of age.GTCS and focal seizures are the most common types.The seizures of most children are easily controlled with the effective treatment of Oxcarbazepine,Valproate sodium,and Levetiracetam.