Human Disease Model Report: epilepsy, nocturnal frontal lobe, 5

General Information

Name

epilepsy, nocturnal frontal lobe, 5

FlyBase ID

FBhh0001407

Disease Ontology Term

autosomal dominant nocturnal frontal lobe epilepsy 5

Parent Disease

OMIM

EPILEPSY, NOCTURNAL FRONTAL LOBE, 5; ENFL5

Overview

This report describes epilepsy, nocturnal frontal lobe, 5 (ENFL5), one of several epileptic diseases associated with defects in the human gene KCNT1. DEE14 exhibits autosomal dominant inheritance. KCNT1 encodes an outwardly rectifying potassium channel subunit. There is a single orthologous gene in Drosophila, SLO2, which is also orthologous to human KCNT2.

UAS constructs of the human Hsap\KCNT1 gene have been introduced into flies, including wild-type and variants implicated in human disease; see the 'Disease-Implicated Variants' table below. Using a pan-neuronal drivers, expression of each of the disease-implicated variants results in embryonic lethality; expression restricted to GABAergic neurons results in viable adults that exhibit a seizure phenotype. This system has been used to assess epilepsy drugs most commonly administered to patients with KCNT1-epilepsy.

For information on disease-related studies using the fly SLO2 gene, see human disease model report for seizure-sensitive, potassium channel defects, KCNT1-2-related (FBhh0001405). A complete table of KCNT1 disease-implicated variants studied in flies can be found in that report.

[updated Mar. 2024 by FlyBase; FBrf0222196]

Disease Summary Information

Disease Summary: epilepsy, nocturnal frontal lobe, 5

OMIM report

[EPILEPSY, NOCTURNAL FRONTAL LOBE, 5; ENFL5](https://omim.org/entry/615005)

Human gene(s) implicated

[POTASSIUM CHANNEL, SUBFAMILY T, MEMBER 1; KCNT1](https://omim.org/entry/608167)

Symptoms and phenotype

Nocturnal frontal lobe epilepsy-5 is an autosomal dominant focal epilepsy syndrome characterized by childhood onset of clusters of motor seizures during sleep. Some patients may develop behavioral or psychiatric manifestations and/or intellectual disability. The phenotype is more severe than observed in other genetic forms of ENFL (summary by Heron et al., 2012; pubmed:23086396). [from MIM:615005; 2021.11.11]

(OMIM, 2013-)

Genetics

Nocturnal frontal lobe epilepsy-5 (ENFL5) is caused by heterozygous mutation in the KCNT1 gene. [from MIM:615005; 2021.11.11]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

KCNT1 encodes an outwardly rectifying potassium channel subunit that may co-assemble with other Slo-type channel subunits; activated by high intracellular sodium or calcium levels. [Gene Cards, KCNT1; 2021.11.11]

(FlyBase Curators, 2013-)

External links