Skeletal dysplasia

Gene: FGF4

Green List (high evidence)

The rating of this gene has been updated to green and the mode of inheritance set to BIALLELIC, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.

Created: 11 Mar 2026, 11:31 p.m. | Last Modified: 11 Mar 2026, 11:31 p.m.

Panel Version: 8.37

Comment on list classification: Promoting to amber with a recommendation of green rating following GMS review. 2 unrelated cases plus a supportive mouse model.

Created: 14 Jul 2025, 9:23 p.m. | Last Modified: 14 Jul 2025, 9:23 p.m.

Panel Version: 8.6

Associated with Short-rib thoracic dysplasia 22 without polydactyly, OMIM:621260 (AR)

PMID: 40259859 - Watts et al 2025 report 2 unrelated families (1 in the 100,000 Genomes project) with a clinical diagnosis of thoracic dystrophy with associated respiratory insufficiency.

Family 1 - 2 affected boys clinically suspected to have Jeune syndrome, and 3 unaffected children born to healthy consanguineous 2nd cousin parents. Both affected individuals had narrow/small thorax and short ribs (11 pairs). 2nd child died at 3  months from respiratory infection. Both affected children were homozygous for a missense variant in FGF4 (c.256C>T p.(Leu86Phe)). Parents are confirmed carriers and 2 of the 3 unaffected siblings do not carry the variant.

Family 2 - 1 male with a chest shape suggesting thoracic dystrophy and a clinical suspicion of Jeune syndrome. A biallelic missense variant in FGF4 NM_002007.4:c.611C>A p.(Pro204His) was identified. Parents were both heterozygous carriers.

The variants are absent from gnomAD and UK Biobank and are predicted to be damaging by multiple in silico tools.

PMID: 33210601 - Anderson et al 2020 - Mouse mutants lacking Fgf4 Fgf4 show a variety of segmentation defects in the cervical and thoracic vertebrae with 100% penetrance.
Sources: Literature

Created: 14 Jul 2025, 9:22 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Short-rib thoracic dysplasia 22 without polydactyly, OMIM:621260; Jeune syndrome, MONDO:0018770

Publications

• 40259859
• 33210601