Early onset or syndromic epilepsy

Gene: ELAVL2

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (at least four unrelated cases and functional studies) available for the association of monoallelic ELAVL2 variants with epilepsy. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 13 Aug 2026, 12:25 p.m. | Last Modified: 13 Aug 2026, 12:25 p.m.

Panel Version: 9.61

PMID:42556336 (2026) reported 13 previously unpublished individuals, plus three previously reported cases, with de novo heterozygous ELAVL2 variants presenting with a neurodevelopmental disorder in which epilepsy was a recurrent, though not universal, feature—seizures were reported in 4 of 13 newly described individuals (1/7 with truncating/structural variants and 3/6 with missense variants), comprising absence, febrile, tonic-clonic, and spasms (West syndrome in one individual with a missense variant). All affected individuals additionally presented with developmental delay, intellectual disability of varying severity, motor and speech delay, autism spectrum diagnoses, sleep disturbance, sensory processing abnormalities (hyper- or hyposensitivity to sound, texture, and light), and behavioural/emotional dysregulation.

Drosophila loss-of-function models of the ELAVL2 ortholog fne (null mutant and pan-neuronal RNAi knockdown) showed significantly increased seizure-like behaviour (both duration and frequency) following mechanical induction, establishing a causal functional link between ELAVL2 loss-of-function and seizure susceptibility.

This gene has not yet been associated with relevant phenotypes either in OMIM, ClinGen or Gene2Phenotype (last accessed 13 August 2026).
Sources: Literature

Created: 13 Aug 2026, 11:36 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 42556336