Paediatric disorders - additional genes

Gene: EIF3A

Green List (high evidence)

Comment on list classification: There are four unrelated individuals reported with monoallelic EIF3A variants and with a complex phenotype involving mild developmental/ speech delays, cardiac anomalies and craniofacial dysmorphism. The phenotypes displayed do not fit into the scope of intellectual disability panel, but fit into the scope of R27 Paediatric disorders super panel. Hence, this gene should be promoted to green rating on this panel in the next GMS update.

Created: 6 Jan 2026, 3:19 p.m. | Last Modified: 6 Jan 2026, 6:09 p.m.

Panel Version: 7.28

PMID:41033306 (2025) reported four unrelated individuals identified with heterozygous loss-of-function variants in EIF3A gene (2.58 kpb intragenic deletion, p.Glu99Lysfs*3, p.Cys404Ter & p.Arg1030Ter). The phenotypes were varied, but included cardiac defects, craniofacial dysmorphisms and mild developmental delays.

Cardiac features: Two individuals presented with tetralogy of Fallot, a third individual had a perimembranous VSD, ASD, and patent foramen ovale and the fourth individual presented with VSD, right-sided aortic arch, and a vascular ring.

Neurodevelopmental features: One individual had a history of speech and language delays but is currently within normal limits. Another was suspected of having a learning difficulty, although all developmental milestones were met. Third exhibited mild articulation issues, and fourth was reported to have a developmental delay. Seizures were reported in one of these individuals.

Functional evidence was available from zebrafish model with mutations in the orthologous eif3s10 gene, which resulted in developmental abnormalities, including thin heart tubes, lack of craniofacial cartilage, and embryonic lethality.

This gene has been associated with relevant phenotypes in Gene2Phenotype (with 'moderate' rating on the DD panel), but not yet in OMIM (last accessed 06 January 2026).
Sources: Literature

Created: 6 Jan 2026, 3:15 p.m. | Last Modified: 6 Jan 2026, 6:08 p.m.

Panel Version: 7.28

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
syndromic disease, MONDO:0002254

Publications

• 41033306