학술논문
De novo gain-of-function variants in KCNT2 as a novel cause of developmental and epileptic encephalopathy.
Document Type
Journal Article
Author
Source
Subject
*POTASSIUM
*PEOPLE with epilepsy
*QUINIDINE
*SPASMS
*PHARMACOLOGY
*
*
*
*
Language
ISSN
0364-5134
Abstract
Variants in several potassium channel genes have been found in developmental and epileptic encephalopathies (DEE). We report on 2 females with de novo variants in KCNT2 with West syndrome followed by Lennox-Gastaut syndrome or with DEE with migrating focal seizures. After in vitro analysis suggested quinidine-responsive gain-of-function effects, we treated 1 of the girls with quinidine add-on therapy and achieved marked clinical improvements. This suggests that the new spectrum of KCNT2-related disorders do not only share similar phenotypic and in vitro functional and pharmacological features with previously known KCNT1-related disorders, but also represents a further example for possible precision medicine approaches. Ann Neurol 2018;83:1198-1204. [ABSTRACT FROM AUTHOR]