Genetic potassium channel-associated epilepsies: Clinical review of the K family.

Nicholas M Allen, Sarah Weckhuysen, Kathleen Gorman, Mary D King, Holger Lerche

Journal: European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society 2020;24():105-116

PMID: 31932120

Full Text on Elsevier Science View on PubMed

Abstract

Next-generation sequencing has enhanced discovery of many disease-associated genes in previously unexplained epilepsies, mainly in developmental and epileptic encephalopathies and familial epilepsies. We now classify these disorders according to the underlying molecular pathways, which encompass a diverse array of cellular and sub-cellular compartments/signalling processes including voltage-gated ion-channel defects. With the aim to develop and increase the use of precision medicine therapies, understanding the pathogenic mechanisms and consequences of disease-causing variants has gained major relevance in clinical care. The super-family of voltage-gated potassium channels is the largest and most diverse family among the ion channels, encompassing approximately 80 genes. Key potassium channelopathies include those affecting the K, K and K families, a significant proportion of which have been implicated in neurological disease. As for other ion channel disorders, different pathogenic variants within any individual voltage-gated potassium channel gene tend to affect channel protein function differently, causing heterogeneous clinical phenotypes. The focus of this review is to summarise recent clinical developments regarding the key voltage-gated potassium (K) family-related epilepsies, which now encompasses approximately 12 established disease-associated genes, from the KCNA-, KCNB-, KCNC-, KCND-, KCNV-, KCNQ- and KCNH-subfamilies.

Address: Department of Paediatrics, National University of Ireland, Galway, Ireland; Department of Paediatrics (Neurology), Galway University Hospital, Ireland; Regenerative Medicine Institute (REMEDI), National University of Ireland, Galway, Ireland. Electronic address: [email protected].; Neurogenetics Group, Center for Molecular Neurology, VIB-University of Antwerp, Antwerp, Belgium; Department of Neurology, University Hospital Antwerp, Antwerp, Belgium.; Department of Paediatric Neurology & Clinical Neurophysiology, Children's Health Ireland at Temple Street, Dublin 1, Ireland; University College Dublin School of Medicine and Medical Science, University College, Dublin, Ireland.; Department of Neurology and Epileptology, Hertie Institute of Clinical Brain Research, University of Tubingen, Germany.

DOI: 10.1016/j.ejpn.2019.12.002