Early onset or syndromic epilepsy
Gene: KCNT1
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Proposed gain of function mechanism. Misenses are reported in association with epilepsy.AD EIEE14 & AD nocturnal frontal lobe epilepsy type 5 (ENFL5). EIEE14 presents as malignant migrating partial seizures of infancy. Barcia et al, 2012 - 4 diff de novo het mutations in KCNT1 - functional work done. Vanderver et al, 2014 - de novo het mutation. Ishii et al, 2013 - 2 unrelated girls - same de novo het missense mutation. ENFL5 - AD focal epilepsy syndrome - childhood onset of motor clusters in sleep - Derry et al, 2008 & Heron et al, 2012 - 4 unrelated families all had het mutations.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Epilepsy, nocturnal frontal lobe, 615005; Epileptic encephalopathy, early infantile, 614959
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype -please provide details in the comments
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epileptic encephalopathy, early infantile, 14; Epilepsy, nocturnal frontal lobe, 5
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epileptic encephalopathy, early infantile, 14; Epilepsy, nocturnal frontal lobe, 5
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epileptic encephalopathy, early infantile, 14; Epilepsy, nocturnal frontal lobe, 5
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes
Epileptic encephalopathy, early infantile, 14; Epilepsy, nocturnal frontal lobe, 5
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
615005
Publications
Comment when marking as ready: A confirmed DD gene for malignant migrating partial seizures of infancy and severe autosomal dominant noctural frontal lobe epilepsy, and all reviewers agree this should be green on this panel. Activating variants cause malignant migrating partial seizures of infancy, and missense/in frame variants severe autosomal dominant noctural frontal lobe epilepsy.Created: 20 Jan 2016, 12:45 p.m.
Comment on phenotypes: Sourced from reviewers, OMIM and G2P.Created: 20 Jan 2016, 12:36 p.m.
Comment on mode of inheritance: Monoallelic confirmed for both phenotypes on G2P and OMIM. Not on the imprinted gene list.Created: 20 Jan 2016, 12:34 p.m.
Source Wessex and West Midlands GLH was added to KCNT1.
Source NHS GMS was added to KCNT1.
Ellen McDonagh: Comment on mode of inheritance
NIHRBR-RD Consortium SPEED_v3.0_20170404 was added to KCNT1. Panel: Genetic Epilepsy Syndromes
Victorian Clinical Genetics Services was added to KCNT1. Panel: Genetic Epilepsy Syndromes
KCNT1 was added to Genetic Epilepsy Syndromes panel. Sources: Expert Review Green,Expert,UKGTN,Radboud University Medical Center, Nijmegen
KCNT1 was created by Sarah Leigh