Early onset or syndromic epilepsy

Gene: KCNT2

Comment on phenotypes: OMIM phenotype updated 27th Feb 2026.

Created: 27 Feb 2026, 1:37 p.m. | Last Modified: 27 Feb 2026, 1:37 p.m.

Panel Version: 8.122

Green List (high evidence)

Loss-of-function and gain-of-function variants reported to cause phenotype (Cioclu et al., 2023 PMID: 37062836).

Created: 4 Feb 2026, 11:29 a.m. | Last Modified: 4 Feb 2026, 11:29 a.m.

Panel Version: 8.106

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Mode of pathogenicity
Other

I don't know

Kept rating as Green based on Green post-Webex review from Helen Lord.

Created: 9 Sep 2019, 10:25 a.m. | Last Modified: 9 Sep 2019, 10:25 a.m.

Panel Version: 1.315

Review and rating collated by Helen Lord (Oxford University Hospitals NHS Foundation Trust, 2019_08_30) on behalf of West Midlands, Oxford and Wessex GLH for GMS Neurology specialist test group. This gene was added to the Genetic epilepsy syndromes panel after the initial panel was reviewed by West Midlands, Oxford and Wessex GLH: this gene was therefore reviewed following the group Webex call on 2019_08_08 for Clinical Indication R59 Early onset or syndromic epilepsy.

Created: 5 Sep 2019, 2:26 p.m. | Last Modified: 5 Sep 2019, 2:26 p.m.

Panel Version: 1.262

Green List (high evidence)

AD EIEE57. Gururaj et al, 2017 (29069600) - 4 year old boy with intractable seizures ass with developmental regression - misnly prolonged tonic but also had myoclonic jerks and atypicalabsence. De novo het missense variant, F240L. In vitro functional expression studies showed decreased expression of mutant protein as well as signif altered ion selectivity. Ambrosino et al, 2018 (29740868) - 2 unrelated males, both had seizures and both had de novo missense variants R190H and R190P.

Created: 5 Sep 2019, 2:22 p.m. | Last Modified: 5 Sep 2019, 2:22 p.m.

Panel Version: 1.261

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

KCNT2 identified by external reviewer.
Gururaj et al (PMID:29069600) reported on a male child with early infantile epileptic encephalopathy. Following trio sequencing a de novo hetrozygous variant (NM_001287819.1:c.[720T > A];p.[(Phe240Leu)] was identified in KCNT2. Some functional work was performed on Chinese hamster ovary (CHO) cells and Xenopus laevis oocyte which confirmed that Phe-240 is critical in gating and expression.
Ambrosino et al (PMID:29740868) reported on two female children with de novo variants in KCNT2 one individual with West syndrome followed by Lennox-Gastaut syndrome the other with developmental and epileptic encephalopathies with migrating focal seizures.
Both individuals and their parents underwent sequencing, one individual had a KCNT2 de novo missense variant, c.569G>A, p.(Arg190His) and the other had a KCNT2 de novo missense variant, c.569G>C, p.(Arg190Pro). Some function work on HEK-293 cells were performed.
KCNT2 is included on some diagnostic panels.

KCNT2 has sufficient evidence from (>3) unrelated families and some functional work to support this to be classified as a Green gene.

Created: 4 Jul 2019, 3:17 p.m. | Last Modified: 4 Jul 2019, 3:18 p.m.

Panel Version: 0.55

Green List (high evidence)

Amplexa CHE-114 epilepsy panel
Sources: Expert list

Created: 21 Feb 2019, 2:13 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
epilepsy

Publications

• 29740868
• 29069600

Variants in this GENE are reported as part of current diagnostic practice