Skeletal dysplasia

Gene: SMAD3

Green List (high evidence)

Overgrowth (tall stature) syndromes with skeletal involvement. >3 cases; Review on behalf of Tracy Lester

Created: 6 Mar 2019, 11:44 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Loeys-Dietz syndrome 3 613795

I don't know

Note one case with a biallelic variant reported:
PMID: 32935439 - Baskin et al 2020 - first report of a LDS patient with biallelic SMAD3 variants (affecting splice site). Proband had classic Loeys-Dietz features, including dysmorphic facial features, significant scoliosis, and pectus excavatum, arachnodactyly, severe aortic root dilation, and diffuse arterial tortuosity. His parents are each heterozygous for the likely pathogenic variant and are more mildly affected.

Created: 28 Jul 2021, 12:24 a.m. | Last Modified: 28 Jul 2021, 12:24 a.m.

Panel Version: 2.109

This gene was part of an initial gene list collated by Tracy Lester, Oxford Medical Genetics Laboratories, Oxford University Hospitals NHS Foundation Trust, February 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: SMAD3; Initial rating suggestion: green

Created: 6 Mar 2019, 11:37 a.m.

Comment when marking as ready: Associated with phenotype in OMIM and G2P. Numerous variants reported

Created: 1 Aug 2016, 6:56 a.m.

Green List (high evidence)

Tier 3

Created: 17 Jun 2016, 8:08 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Loeys-Dietz syndrome 3 613795

Variants in this GENE are reported as part of current diagnostic practice