Paediatric disorders - additional genes

Gene: EIF3B

Green List (high evidence)

Comment on list classification: There are 14 unrelated individuals reported with monoallelic EIF3B variants and with a complex phenotype involving cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioural abnormalities. 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, 6:02 p.m. | Last Modified: 6 Jan 2026, 6:10 p.m.

Panel Version: 7.28

PMID:41033306 (2025) reported 14 unrelated individuals with heterozygous de novo or loss-of-function variants in EIF3B gene. The clinical phenotype varied but predominantly included cardiac defects, craniofacial dysmorphisms, mild developmental delays, and behavioral abnormalities.

11 of 14 individuals had congenital heart defect including four with tetralogy of Fallot, neurodevelopmental phenotype including developmental delay, speech and language delay, and mild or specific learning disabilities were reported in eight individuals. Behavioral abnormalities, including attention-deficit hyperactivity disorder and autism spectrum disorder, were also noted.

Facial differences were observed in eleven individuals. While features varied, several individuals exhibited differences in the eye region that overlapped with those previously reported in individuals with 7q22.3 micro-deletions, including ptosis, arched eyebrows, downslanting palpebral fissures, hypertelorism, and epicanthal folds. Cleft lip and palate and hearing loss and/or inner and middle ear malformations were reported in four individuals each.

Functional evidence was available from zebrafish model with mutations in the orthologous eif3ba 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, 4:21 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
syndromic disease, MONDO:0002254

Publications

• 41033306