Objective: To identify the pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy (PME). Methods: In this cross-sectional study, 26 PME children (11 boys and 15 girls) sent to neurological outpatient clinics and admitted to wards of the Department of Pediatrics, Peking University First Hospital were enrolled prospectively from January 2014 to October 2018. The pathogenic gene variants of PME children and their parents were identified by Sanger sequencing, next generation sequencing panels of epilepsy or trio-based whole exome sequencing and so on. The genotypes and phenotypes of the PME children were anaylzed. Results: The clinical features of 26 children include myoclonus, multiple types of seizures and progressive neurological regression. Their onset ages ranged from 3 months to 15 years. Several pathogenic gene variants were identified in the 15 patients, including TPP1 gene variantions in 3 patients; NEU1, GBA, TBC1D24 and KCNC1 gene variantions in 2 patients respectively; CLN6, MFSD8, ASAH1 and ATN1 gene variantions in 1 patient respectively. Several variants of uncertain significance were identified in 4 patients, including GOSR2 gene compound heterozygous variants in 2 patients, KCTD7 gene compound heterozygous variants in 1 patient, and compound heterozygous variants of an unreported TARS gene in 1 patient. No pathogenic gene variant was identified in 7 patients. In 15 children with the identified pathogenic gene variants, 5 patients were diagnosed with neuronal ceroid lipofuscinoses (NCL), 2 patients with sialidosis, 2 patients with neuronopathic Gaucher disease, 1 patient with dentatorubral-pallidoluysian atrophy (DRPLA), and 1 patient with spinal muscular atrophy-progressive myoclonic epilepsy (SMA-PME). Conclusions: PME include a group of diseases with genetic heterogeneity. Identification of the pathogenic gene variants of PME could help to predict the prognosis and guide the genetic counseling.
目的： 总结进行性肌阵挛癫痫（PME）患儿的致病基因和临床表型特点。 方法： 采用横断面设计的方法，2014年1月至2018年10月前瞻性收集在北京大学第一医院儿科神经门诊及病房临床诊断为PME的患儿，共收集PME患儿26例，男11例、女15例。通过目的基因一代测序、靶向捕获二代测序癫痫基因检测包或家系全外显子组等方法，对患儿及其父母进行致病基因检测，并对患儿的基因型与表型特点进行分析。 结果： 26例PME患儿起病年龄为3月龄至15岁，临床特点包括肌阵挛、多种类型的癫痫发作和进行性神经功能倒退。明确致病基因的患儿15例，包括TPP1基因3例，NEU1、GBA、TBC1D24、KCNC1基因各2例，CLN6、MFSD8、ASAH1和ATN1基因各1例。4例患儿发现可能的致病基因，其中2例GOSR2基因复合杂合变异，1例KCTD7基因复合杂合变异，1例国际未报道的TARS基因复合杂合变异。7例患儿尚未明确致病基因。15例致病基因明确的患儿中，符合神经元蜡样质脂褐质沉积症（NCL）者5例，唾液酸沉积症、神经型戈谢病各2例，齿状核红核苍白球路易体萎缩症、脊肌萎缩症-进行性肌阵挛癫痫各1例。 结论： PME包括一组具有遗传异质性的神经遗传病，明确PME的致病基因对判断预后及遗传咨询具有重要意义。.
Keywords: Genes; Myoclonic epilepsies, progressive; Myoclonus.