Early onset or syndromic epilepsy

Gene: KLHL20

This gene is not currently associated with a disease phenotype in OMIM, but checked PMID:36214804 to make sure it is the same gene listed in the publication as on this panel and it is, so added the gene-checked tag.

Created: 16 Oct 2023, 7:34 p.m. | Last Modified: 16 Oct 2023, 7:34 p.m.

Panel Version: 4.118

Green List (high evidence)

The rating of this gene has been updated to Green following NHS Genomic Medicine Service approval.

Created: 11 Oct 2023, noon | Last Modified: 11 Oct 2023, noon

Panel Version: 4.110

Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel review.
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Sleyp et al. 2022 (PMID: 36214804) reported on 14 patients with de novo missense variants who all presented with mild to severe ID, seizures, ASD, hyperactivity, and dysmorphic facial features. One variant (c.1069G>A, p.Gly357Arg) was recurrent in 11/14 cases but all variants clustered in the Kelch-type β-propeller domain (substrate binding surface) of the KLHL20 protein. No functional studies were performed but given the overlap in clinical presentation observed in patients with the same recurrent variant but also multiple different variants, its worth including as diagnostic-grade.

Created: 19 Dec 2022, 3:24 p.m. | Last Modified: 19 Dec 2022, 3:24 p.m.

Panel Version: 3.11

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

14 cases with mostly recurrent missense variant in this gene is reported.
Sources: Literature

Created: 8 Dec 2022, 11:17 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
developmental disorder with intellectual disability, epilepsy, and autism spectrum disorder

Publications

• 36214804

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments