Ehlers Danlos syndrome with a likely monogenic cause

Gene: NOTCH1

Comment on phenotypes: Previous phenotypes:
Connective Tissue Disorders;Aortic valve disease 1, 109730;Familial thoracic aortic aneurysm;Bicuspid, or bicommissural, aortic valve (BAV)

Created: 18 Mar 2021, 2:31 p.m. | Last Modified: 18 Mar 2021, 2:31 p.m.

Panel Version: 2.56

I don't know

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: NOTCH1; Suggested initial gene rating: red

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

Red List (low evidence)

Following discussion with Dr Diana Johnson - rate red

Created: 3 Apr 2019, 3:44 p.m.

No found any pathogenic mutations in service history. Phenotype not overlapping with EDS.

Created: 24 Jan 2019, noon

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Bicuspid, or bicommissural, aortic valve (BAV)

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

Red List (low evidence)

There is a clear gene-disease association (BAV) but in view of the relatively discrete vascular phenotype, this gene would be best placed on the FTAAD panel rather than as a differential diagnosis for those with connective tissue disease. Those with a vascular phenotype in addition would be offered the FTAAD panel in addition. D/W Neeti Ghali, EDS Specialist Clinic who is in agreement.

Created: 25 Jul 2017, 1:01 p.m.

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

Comment on list classification: Changed from Green to Amber based due to the relatively discrete vascular phenotype

Created: 25 Jul 2017, 12:59 p.m.

Green List (high evidence)

Green List (high evidence)

Associated with FTAA. Review from EDS National Diagnostic Service North West London Hospital NHS Trust: Dr Angela Brady FRCP PhD, Consultant Clinical Geneticist; Dr Neeti Ghali MBChB MD, Consultant Clinical Geneticist; Dr Fleur S van Dijk MD PhD, Consultant.

Created: 7 Jul 2017, 6:29 p.m.