结节性硬化症伴癫痫患儿临床特征和基因型分析

摘要 目的：探讨结节性硬化症（TSC）伴癫痫患儿的临床特征和基因型特点，旨在了解 TSC伴癫痫患儿的临床表现，以及表型与基因型的相关性，为临床诊治提供更有效的方案。方法：回顾性分析 2019年 12月至 2021年 1月安徽省儿童医院神经内科收治的 10例 TSC伴癫痫患儿的临床表现，采用芯片捕获高通量测序以及 Sanger测序验证，对 TSC伴癫痫患儿及父母进行基因检测，分析其临床及遗传变异的特征。结果：10例中男性 4例，女性 6例，首次发作痉挛 3例，局灶性 7例，70.00%首发年龄小于 1岁。临床表现：90.00%皮肤病变，80.00%心脏横纹肌瘤，20.00%眼底异常，未见肾脏、肝脏、肺脏病变。视频脑电图显示 60.00%痫样波位于额颞区，100.00%伴神经影像学皮层 /皮层下异常，90.00%双侧室管膜 /室管膜下异常，10.00%室管膜下巨细胞星形细胞瘤。研究患儿均完善基因检测，3例为 TSC1基因突变，7例为 TSC2突变，包括错义、移码及剪接位点突变，2例检测出家族变异，7例均未检测出家族变异。结论：TSC伴癫痫患儿男女发病无明显差异性，散发病例多见，发病年龄多为 1岁内，首次发作常为局灶性。视频脑电图痫样波额颞区为主，头颅影像学多为皮层 /皮层下及双侧室管膜 /室管膜下异常。TSC2突变较 TSC1突变常见，临床表现严重，痉挛发生率高，发病年龄小，多控制不佳。早期基因检测，对于发病年龄小，疗效欠佳患儿尤为重要。

Clinical Characteristics and Genotype Analysis of Children with Tuberous Sclerosis Complex with Epilepsy

ABSTRACT Objective: To explore the clinical characteristics and genotype characteristics of children with tuberous sclerosis complex (TSC) with epilepsy, in order to understand the clinical manifestations of children with TSC with epilepsy, and the correlation between phenotype and genotype, so as to provide a more effective scheme for clinical diagnosis and treatment. Methods: The clinical manifestations of 10 children with TSC with epilepsy who were treated in the Department of Neurology of Anhui children''s Hospital from December 2019 to January 2021 were analyzed retrospectively. The gene detection was performed on children with TSC with epilepsy and their parents by chip capture high-throughput sequencing and Sanger sequencing validation, and the characteristics of clinical and genetic variation were analyzed. Results: Among the 10 cases, 4 were male, and 6 were female, 3 were first convulsive, and 7 were focal, and 70.00% initial age were younger than 1 year old. Clinical manifestations: 90.00% skin lesions, 80.00% cardiac rhabdomyoma, 20.00% fundus abnormalities, no kidney, liver, lung lesions. Video electroencephalogram showed 60.00% epileptic wave in frontotemporal region, 100.00% with neuroimaging cortical/subcortical abnormalities, 90.00% bilateral ependymal/subependymal abnormalities, and 10.00% subependymal giant cell astrocytoma. Gene testing was completed in all the children in the study, including 3 cases of TSC1 gene mutation, 7 cases of TSC2 mutation, including missense, frameshifting and splicing site mutation. Family variation was detected in 2 cases, and no family variation was detected in 7 cases. Conclusion: There is no significant difference in the incidence of TSC with epilepsy between male and female, and sporadic cases are more common. The initial age is less than 1 year, and the first onset is often focal. Epileptic wave in video electroencephalogram is dominant in frontotemporal region, and cortical/subcortical and bilateral ependymal/subependymal abnormalities are found in head imaging. TSC2 mutation is more common than TSC1 mutation, with severe clinical manifestations, high incidence of convulsion, younger age of onset and poor control. Early genetic testing is particularly important for children at younger age of onset and with poor efficacy.