[P3-64] Clinical and genetic analysis of KCNQ2 mutation-induced neonatal epileptic disorders
[Introduction] The aim of the study is to reveal clinical features of neonatal epileptic disorders caused by KCNQ2 mutations and analyze anti-epilepsy drugs (AEDs) treatment of KCNQ2 mutation-induced disorders.
[Methodology] Patients were all collected in the Department of Pediatrics, Peking University First Hospital. We conducted clinical and genetic analysis for the neonatal epileptic patients in whom a KCNQ2 mutation was identified by the targeted next generation sequencing.
[Results] We found 14 de novo KCNQ2 missense mutations from 14 patients with neonatal epileptic disorders. These patients had an onset of epilepsy in early infancy (in 6 days of life), followed by developmental delay. Four of 14 patients became seizure-free after the treatment of valproic acid. Literature review was applied to analyze phenotype-genotype relationship, and we found that the mutations associated with early onset epileptic encephalopathy (EOEE, severe phenotype) were mainly distributed at the transmembrane domain S4 and the loop between S5 and S6 of KCNQ2 protein, but a majority of the mutations identified from patients with benign familial neonatal seizures (BFNS, mild phenotype) were at C-terminal region. We found one patient with an intermediate type between EOEE and BFNS in our study, suggesting that KCNQ2 mutation-induced epilepsy may be a continuous spectrum, instead of only two extremes (BFNS and EOEE).
[Conclusions] We expand the EOEE-associated mutation spectrum. Valproic acid may be an optional treatment for the KCNQ2-induced epilepsy. Position of a KCNQ2 mutation may be associated with disease severity. KCNQ2 mutation-induced epilepsy may be a continuous spectrum.
[Methodology] Patients were all collected in the Department of Pediatrics, Peking University First Hospital. We conducted clinical and genetic analysis for the neonatal epileptic patients in whom a KCNQ2 mutation was identified by the targeted next generation sequencing.
[Results] We found 14 de novo KCNQ2 missense mutations from 14 patients with neonatal epileptic disorders. These patients had an onset of epilepsy in early infancy (in 6 days of life), followed by developmental delay. Four of 14 patients became seizure-free after the treatment of valproic acid. Literature review was applied to analyze phenotype-genotype relationship, and we found that the mutations associated with early onset epileptic encephalopathy (EOEE, severe phenotype) were mainly distributed at the transmembrane domain S4 and the loop between S5 and S6 of KCNQ2 protein, but a majority of the mutations identified from patients with benign familial neonatal seizures (BFNS, mild phenotype) were at C-terminal region. We found one patient with an intermediate type between EOEE and BFNS in our study, suggesting that KCNQ2 mutation-induced epilepsy may be a continuous spectrum, instead of only two extremes (BFNS and EOEE).
[Conclusions] We expand the EOEE-associated mutation spectrum. Valproic acid may be an optional treatment for the KCNQ2-induced epilepsy. Position of a KCNQ2 mutation may be associated with disease severity. KCNQ2 mutation-induced epilepsy may be a continuous spectrum.