Genetic and clinical analysis of children with early-onset epilepsy encephalopathy caused by KCNT1 gene mutation / 中华儿科杂志

ABSTRACT

Objective@#To study the mutational characteristics of KCNT1 and its clinical features in children with early-onset epileptic encephalopathy.@*Methods@#Retrospective analysis of clinical data of 175 children with early onset epilepsy from the Department of Pediatrics at Peking University First Hospital from January 2012 to December 2017. Gene-based analysis was performed on children with targeted capture second-generation sequencing and the source of mutations was verified by PCR-Sanger. The clinical features of children with KCNT1 mutation were summarized.@*Results@#In 175 infants with early-onset epileptic encephalopathy, 6 children were found to have KCNT1 mutations, all of which were new mutations with an overall mutation rate of 3.4% (6/175). All the mutations were missense mutations. The age of onset was from 2 days to 32 days. Five children were diagnosed with epilepsy of infancy with migrating focal seizure, one case was diagnosed with epilepsy, focal seizures, focal seizures with generalization. A total of 6 children were treated with multi-antiepileptic drugs. The disease in 4 patients were partially controlled, while in 2 patients, the disease was not significantly alleviated. One patient died of "severe pneumonia" at one year and 4 months of age. Then, four cases were treated with quinidine. The seizure frequency had no change in 3 cases, the frequency decreased and then relapsed in 1 case. The case once ketogenic diet and failed. Ketogenic diet treatment was applied to 5 cases, no significant effect was achieved. All the 6 patients had severe developmental delay. They could not sit alone, follow the light and objects and had no language.@*Conclusions@#The mutation of KCNT1 gene is mainly de novo. The onset of the disease was early, and mostly occurs in neonate and early infancy. The main seizure type was epilepsy of infancy with migrating focal seizure. Patients usually had severe psychomotor developmental delay. Antiepileptic drugs are ineffective. The efficacy of quinidine was not significant. Though, it still need studies on a large sample.