Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K+ channelopathies.
Fiche du document
- doi: 10.1038/s41431-021-00818-9
- issn: 1018-4813
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1038/s41431-021-00818-9
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/33594261
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1476-5438
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_FB1A5B23DB431
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
Sujets proches
Abnormities and deformities Deformities Kalium Defects, Birth Malformations, Congenital Congenital anomalies Developmental abnormalities Congenital abnormalities Anomalies, Congenital Human abnormalities Deformities Birth defects AbnormalitiesCiter ce document
K.W. Gripp et al., « Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3-a subgroup of K+ channelopathies. », Serveur académique Lausannois, ID : 10.1038/s41431-021-00818-9
Métriques
Partage / Export
Résumé
Decreased or increased activity of potassium channels caused by loss-of-function and gain-of-function (GOF) variants in the corresponding genes, respectively, underlies a broad spectrum of human disorders affecting the central nervous system, heart, kidney, and other organs. While the association of epilepsy and intellectual disability (ID) with variants affecting function in genes encoding potassium channels is well known, GOF missense variants in K + channel encoding genes in individuals with syndromic developmental disorders have only recently been recognized. These syndromic phenotypes include Zimmermann-Laband and Temple-Baraitser syndromes, caused by dominant variants in KCNH1, FHEIG syndrome due to dominant variants in KCNK4, and the clinical picture associated with dominant variants in KCNN3. Here we review the presentation of these individuals, including five newly reported with variants in KCNH1 and three additional individuals with KCNN3 variants, all variants likely affecting function. There is notable overlap in the phenotypic findings of these syndromes associated with dominant KCNN3, KCNH1, and KCNK4 variants, sharing developmental delay and/or ID, coarse facial features, gingival enlargement, distal digital hypoplasia, and hypertrichosis. We suggest to combine the phenotypes and define a new subgroup of potassium channelopathies caused by increased K + conductance, referred to as syndromic neurodevelopmental K + channelopathies due to dominant variants in KCNH1, KCNK4, or KCNN3.