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Syndromic disorders caused by gain-of-function variants in KCNH1, KCNK4, and KCNN3—a subgroup of K+ channelopathies
- Source :
- European Journal of Human Genetics, 29, 1384-1395. Nature Publishing Group, European journal of human genetics, vol. 29, no. 9, pp. 1384-1395, European Journal of Human Genetics
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- 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.
- Subjects :
- Adult
Male
0301 basic medicine
Hypertrichosis
Potassium Channels
Adolescent
Small-Conductance Calcium-Activated Potassium Channels
Nails, Malformed
Biology
Article
Craniofacial Abnormalities
03 medical and health sciences
Epilepsy
0302 clinical medicine
Intellectual Disability
Genetics research
Intellectual disability
Genetics
medicine
Humans
Missense mutation
Abnormalities, Multiple
Child
Gene
Genetics (clinical)
Fibromatosis, Gingival
Abnormalities, Multiple/genetics
Abnormalities, Multiple/pathology
Channelopathies/genetics
Channelopathies/pathology
Craniofacial Abnormalities/genetics
Craniofacial Abnormalities/pathology
Ether-A-Go-Go Potassium Channels/genetics
Female
Fibromatosis, Gingival/genetics
Fibromatosis, Gingival/pathology
Gain of Function Mutation
Hallux/abnormalities
Hallux/pathology
Hand Deformities, Congenital/genetics
Hand Deformities, Congenital/pathology
Intellectual Disability/genetics
Intellectual Disability/pathology
Nails, Malformed/genetics
Nails, Malformed/pathology
Phenotype
Potassium Channels/genetics
Small-Conductance Calcium-Activated Potassium Channels/genetics
Thumb/abnormalities
Thumb/pathology
Coarse facial features
medicine.disease
Ether-A-Go-Go Potassium Channels
Paediatric neurological disorders
030104 developmental biology
Thumb
KCNK4
Hallux
Channelopathies
Hand Deformities, Congenital
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14765438 and 10184813
- Volume :
- 29
- Database :
- OpenAIRE
- Journal :
- European Journal of Human Genetics
- Accession number :
- edsair.doi.dedup.....918739748f0fdc6bed9c9af583939241