KCNA1 Gain-of-function Epileptic Encephalopathy Treated with 4-aminopyridine

Overview

Journal Ann Clin Transl Neurol

Specialty Neurology

Date 2023 Feb 16

PMID 36793218

Authors

Peter Muller

Danielle S Takacs

Ulrike B S Hedrich

Rohini Coorg

Laura Masters

Kevin E Glinton

Hongzheng Dai

Jon A Cokley

James J Riviello

Holger Lerche

Edward C Cooper

Affiliations

Soon will be listed here.

Abstract

Precision medicine for Mendelian epilepsy is rapidly developing. We describe an early infant with severely pharmacoresistant multifocal epilepsy. Exome sequencing revealed the de novo variant p.(Leu296Phe) in the gene KCNA1, encoding the voltage-gated K channel subunit K 1.1. So far, loss-of-function variants in KCNA1 have been associated with episodic ataxia type 1 or epilepsy. Functional studies of the mutated subunit in oocytes revealed a gain-of-function caused by a hyperpolarizing shift of voltage dependence. Leu296Phe channels are sensitive to block by 4-aminopyridine. Clinical use of 4-aminopyridine was associated with reduced seizure burden, enabled simplification of co-medication and prevented rehospitalization.

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