Early onset or syndromic epilepsy

Gene: KDM2A

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (5 unrelated patients) for the association of KDM2A gene with epilepsy. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 9 Jan 2026, 3 p.m. | Last Modified: 9 Jan 2026, 3:37 p.m.

Panel Version: 8.91

PMID:41468891 (2025) reported a cohort of 18 unrelated individuals including one foetus with heterozygous de novo variants in KDM2A gene and with a neurodevelopmental disorder.

All individuals, excluding the foetus, exhibited developmental delay and/or intellectual disability, with the severity of developmental delay or intellectual disability ranging from learning disabilities to severe intellectual disability. The majority of individuals were affected by mild developmental delay/intellectual disability (11/17) or learning disabilities (2/17), while four individuals presented with severe developmental delay/intellectual disability.

The other reported phenotypes include microcephaly (six individuals including the foetus - none of them had OFC beyond -3 SD), seizures (five), hypotonia (four), IUGR (eight), short stature (nine), feeding difficulties (six) and dysmorphic facial features (twelve). Seizure types included focal and generalized seizures as well as epileptic spasms. At the last assessment, two individuals continued to experience seizures, while three achieved seizure freedom. In the latter three, the anti-seizure medication was subsequently weaned off without relapse.

The study proposed dual mechanism of pathogenicity: loss of nuclear function for some variants tested and additional cytoplasmic gain-of-function toxicity for c.704C>T (p.Pro235Leu), as eliminating endogenous Drosophila Kdm2 did not produce noticeable neurodevelopmental phenotypes.

This gene has not yet been associated with relevant phenotypes in OMIM (last accessed 09 January 2026), Gene2Phenotype or ClinGen.
Sources: Literature

Created: 9 Jan 2026, 2:58 p.m. | Last Modified: 9 Jan 2026, 3:13 p.m.

Panel Version: 8.91

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 41468891