ABSTRACT
Objective To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation. Methods Twenty－two patients were collected in the Department of Pediatrics,Peking University First Hospital from April 2007 to July 2016. The phenotype－genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 muta﹣tion was identified by the targeted next generation sequencing. Results Twenty－two de noνo KCNQ2 missense muta﹣tions from 22 patients with neonatal/infantile epileptic disorders were found. These patients had an onset of epilepsy in early infancy(median age:2 days). The seizure type of the first onset was mainly focal seizure. Atypical absence epi﹣lepsy,a novel phenotype of KCNQ2 mutation－induced epilepsies was found. The mortality of these patients was high,as 5 patients of the 22 patients died in the follow－up period,4 of which might result from sudden unexpected death in epi﹣lepsy. In the 22 patients,8 patients with anti－epileptic monotherapy became seizure－free. Of the 8 patients with a monotherapy,3 patients were treated with valproic acid and no clinical onset was observed. Conclusions This study expands the phenotype of KCNQ2－related epileptic disorders. These patients have high mortality. Valproate acid is the potentially effective monotherapy for these patients.
ABSTRACT
Objective@#To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation.@*Methods@#Twenty-two patients were collected in the Department of Pediatrics, Peking University First Hospital from April 2007 to July 2016.The phenotype-genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 mutation was identified by the targeted next generation sequencing.@*Results@#Twenty-two de novo KCNQ2 missense mutations from 22 patients with neonatal/infantile epileptic disorders were found.These patients had an onset of epilepsy in early infancy (median age: 2 days). The seizure type of the first onset was mainly focal seizure.Atypical absence epilepsy, a novel phenotype of KCNQ2 mutation-induced epilepsies was found.The mortality of these patients was high, as 5 patients of the 22 patients died in the follow-up period, 4 of which might result from sudden unexpected death in epilepsy.In the 22 patients, 8 patients with anti-epileptic monotherapy became seizure-free.Of the 8 patients with a monotherapy, 3 patients were treated with valproic acid and no clinical onset was observed.@*Conclusions@#This study expands the phenotype of KCNQ2-related epileptic disorders.These patients have high mortality.Valproate acid is the potentially effective monotherapy for these patients.
ABSTRACT
Epilepsies associated with KCNQ2 are a spectrum of disorders,and KCNQ2 mutations lead to a variety of phenotypes from the severest to the mildest,from early onset epileptic encephalopathy (EOEE) to benign familial neonatal convulsion (BFNC).The type and the position of KCNQ2 mutations may be associated with phenotypes,and provide a clue for assessing prognosis.KCNQ2 mutations lead to the reduced protein expression,abnormal distribution of potassium channels or decreased currents of potassium channels.It is the potential mechanism that KCNQ2 mutations cause different phenotypes.Recent studies have also found that KCNQ2 mutations may trigger seizures by enhancing potassium channel currents;however it needs further studies to verify.