[Pathogenic gene variants and clinical phenotype features of 26 children with progressive myoclonic epilepsy]

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.