J Clin Neurol.  2024 Jul;20(4):402-411. 10.3988/jcn.2023.0435.

Unusual Voltage-Gated Sodium and Potassium Channelopathies Related to Epilepsy

• Shin HJ
• Ko A
• Kim SH
• Lee JS
• Kang HC

• KMID: 2556901
• DOI: http://doi.org/10.3988/jcn.2023.0435

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 lesscommon 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.

Keyword

channelopathy; epilepsy; genetics