Unusual Voltage-Gated Sodium and Potassium Channelopathies Related to Epilepsy

Abstract

Background and Purpose There is extensive literature on monogenic epilepsies caused by mutations in familiar channelopathy genes such as SCN1A . However, information on other less-common channelopathy genes is scarce. This study aimed to explore the genetic and clinical characteristics of patients diagnosed with unusual voltage-gated sodium and potassium channelopathies related to epilepsy. Methods This observational, retrospective study analyzed pediatric patients with epilepsy who carried pathogenic variants of unusual voltage-gated sodium and potassium channelopathy genes responsible for seizure-associated phenotypes. Targeted next-generation sequencing (NGS) panel tests were performed between November 2016 and June 2022 at Severance Children’s Hospital, Seoul, South Korea. Clinical characteristics and the treatment responses to different types of antiseizure medications were further analyzed according to different types of gene mutation. Results This study included 15 patients with the following unusual voltage-gated sodium and potassium channelopathy genes: SCN3A ( n =1), SCN4A ( n =1), KCNA1 ( n =1), KCNA2 ( n =4), KCNB1 ( n =6), KCNC1 ( n =1), and KCNMA1 ( n =1). NGS-based genetic testing identified 13 missense mutations (87%), 1 splice-site variant (7%), and 1 copy-number variant (7%). Developmental and epileptic encephalopathy was diagnosed in nine (60%) patients. Seizure freedom was eventually achieved in eight (53%) patients, whereas seizures persisted in seven (47%) patients. Conclusions Our findings broaden the genotypic and phenotypic spectra of less-common voltage-gated sodium and potassium channelopathies associated with epilepsy.

Time to Open the Channel to Elucidate Pathomechanisms That Underlie Neurological Disorders Related to Channelopathies

“…The authors of the article “Unusual Voltage-Gated Sodium and Potassium Channelopathies Related to Epilepsy” investigated the genetic and clinical characteristics of pediatric patients with epilepsy who carry pathogenic variants in less-common genes relating to voltage-gated sodium and potassium channels. 2 That retrospective study analyzed medical records of patients who visited a tertiary hospital in South Korea during 2016–2022. It aimed to resolve the knowledge gap regarding these rare channelopathies and their response to antiseizure medications (ASMs) and included 15 pediatric patients diagnosed with epilepsy associated with mutations in the SCN3A , SCN4A , KCNA1 , KCNA2 , KCNB1 , KCNC1 , and KCNMA1 genes.…”