Ectodermal dysplasia

Gene: FOSL2

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 10 Dec 2025, 3:49 p.m. | Last Modified: 10 Dec 2025, 3:49 p.m.

Panel Version: 4.19

Comment on list classification: As reviewed by Dmitrijs Rots, there is sufficient evidence available for the association of this gene with green rating in the next GMS update.

Created: 3 Oct 2024, 2:39 p.m. | Last Modified: 3 Oct 2024, 2:39 p.m.

Panel Version: 3.33

PMID:36197437 reported 11 individuals from 10 unrelated families with heterozygous PTC variants (4 frameshift and 3 nonsense) in the last exon of FOSL2 gene. They all had a strikingly similar phenotype characterized by prenatal growth retardation, localized cutis scalp aplasia with or without skull defects, neurodevelopmental delay with autism spectrum disorder, enamel hypoplasia, and congenital cataracts.

All individuals except one had a congenital aplasia cutis of variable size along the midline of the scalp and 8 out of 9 individuals had tooth enamel hypoplasia and discoloration. Multiple other ectodermal features such as small brittle nails, hypotrichosis/hypertrichosis and lichen sclerosis were also reported.

This gene has been associated with relevant phenotypes in both OMIM (MIM #620789) and Gene2Phenotype (with 'moderate' rating on the DD panel).

Created: 3 Oct 2024, 2:38 p.m. | Last Modified: 3 Oct 2024, 2:38 p.m.

Panel Version: 3.30

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Aplasia cutis-enamel dysplasia syndrome, OMIM:620789

Publications

• 36197437

Green List (high evidence)

Already in OMIM as Aplasia cutis-enamel dysplasia syndrome. PMID: 36197437 described 10 cases with NDD and aplasia cutis and truncating variants in the last exon of FOSL2.
Sources: Literature

Created: 28 Aug 2024, 6:24 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Aplasia cutis-enamel dysplasia syndrome

Publications

• PMID: 36197437

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments