Early onset or syndromic epilepsy

Gene: CELF4

I don't know

Additional comments from reviewing GLHs: gnomad data would make this difficult to classify variants (gnomADv4.1.0 pLI score). All ClinVar variants are VUS.

Created: 11 Mar 2026, 4 p.m. | Last Modified: 11 Mar 2026, 4 p.m.

Panel Version: 8.137

After NHS Genomic Medicine Service consideration, the rating of this gene has not been changed and remains amber.

Created: 11 Mar 2026, 3:39 p.m. | Last Modified: 11 Mar 2026, 3:39 p.m.

Panel Version: 8.134

Comment on list classification: There is sufficient evidence available (nine unrelated cases with seizures) for the promotion of this gene to green rating on this panel in the next GMS update.

Created: 20 Jun 2025, 6:36 p.m. | Last Modified: 20 Jun 2025, 6:36 p.m.

Panel Version: 8.5

PMID:40108438 reported 15 patients with heterozygous missense or loss-of-function variants clustering in the N-terminal of the CELF4 gene. Most patients presented with neurodevelopmental disorders including global developmental delay (12 patients), intellectual disability (8, of which moderate in 2, mild in 3, and severity not defined in 3), seizures (9) and overweight/obesity (10) that began in childhood. Clinical features are similar to the reported celf4-mouse mutant phenotype.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature

Created: 20 Jun 2025, 6:30 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
neurodevelopmental disorder, MONDO:0700092

Publications

• 40108438