Ehlers Danlos syndrome with a likely monogenic cause

Gene: SMAD4

I don't know

Comment on list classification: Following discussion in the GMS musculoskeletal specialist test group Webex on 2019-06-04, it was decided to remove this gene from the panel as there is not enough overlap with the EDS phenotype.

Created: 11 Jun 2019, 11:09 a.m.

This gene was part of an initial gene list collated by Duncan Baker, Sheffield Diagnostic Genetics Service, January 2019 on behalf of the GMS Musculoskeletal Specialist Group; Gene symbol submitted: SMAD4; Suggested initial gene rating: red

Created: 3 Apr 2019, 3:41 p.m.

Red List (low evidence)

D/w Dr Diana Johnson, not enough overlap with EDS features.
e.g. PMID: 24525918: Seven of the 34 individuals in the study (21%), from five separate families, had documented evidence of connective tissue findings.

Created: 24 Jan 2019, 11:51 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
juvenile polyposis syndrome (JP) and hereditary hemorrhagic telangiectasia (HHT); ~20% with connective tissue features.

Green List (high evidence)

Green List (high evidence)

Green List (high evidence)

In consultation with the clinical team it was decided to include this gene, due to the clinical overlap of the phenotype with EDS

Created: 24 May 2017, 1:11 p.m.

Refer to clinical team for further discussion on wether we should include this gene on the EDS panel. There is clinical overlap between EDS and other Heritable Connective Tissue Disorders.

Created: 28 Apr 2017, 11:50 a.m.

SMAD4 is part of the TGFβ pathway with integral role of the latter in Thoracic Aortic Aneurysms and Aortic Dissections (TAAD), including Marfan and Loeys-Dietz syndrome.

Created: 26 Apr 2017, 12:29 p.m.