Ehlers-Danlos syndrome (EDS)

Background

This study will investigate the genetic basis of rare inherited connective tissue conditions, mainly the Ehlers-Danlos syndromes (EDS) and those with overlapping phenotypes, which includes familial thoracic aortic aneurysm/dissection (TAAD).

These are diseases, which share a generalised connective tissue weakness (connective tissue collectively describes the elements which keep the structures of the body together). These can mainly lead to the symptoms of Ehlers-Danlos syndrome, including: vascular fragility (predisposing an individual to aneurysm and rupture of blood vessels), hypermobility (loose-jointedness), hyper-extensible skin and other effects. Furthermore, a similar mechanism is thought to underlie a significant familial predisposition to aneurysm/dissection of the thoracic aorta. These conditions often present at a young age and are associated with premature mortality.

We do not currently have a full understanding of which genes are responsible in the various types of EDS or familial TAAD and approximately 70-80% of patients remain undiagnosed, even after sequencing the known causative genes. Therefore, there is a considerable gap in our knowledge of the underlying genetic cause and mechanisms leading to these rare but severe diseases.

Whole exome sequencing will help to identify hitherto undiscovered genes underlying EDS and familial TAAD, thereby providing insight into the molecular pathways underlying these conditions. There will be a direct translational benefit to patients and their relatives by providing a number of undiagnosed individuals with a specific molecular diagnosis, leading to preventative family screening, risk-stratification and prognostication. Molecular genetic characterisation would complement the current clinical classification and treatment of EDS, which is limited, and, for TAAD provide novel insights into disease prognosis, upon which surgical management hinges.

Recruitment Criteria:

Inclusion Criteria
Individuals of any age with a clinically apparent or suspected Mendelian trait.
Affected relatives of any age of the index case
Unaffected relatives of any age of the index case

Exclusion Criteria:
Individuals with known HIV, Hepatitis B & C, Creutzfeldt-Jakob disease

Centres at which EDS is currently recruiting:

Imperial College Healthcare NHS Trust, London
Newcastle upon Tyne Hospitals NHS Foundation Trust
Northwick Park and St Marks Hospitals Clinical Genetics Centre, London
Salisbury NHS Foundation Trust
University College London Hospital, London
University Hospital Southampton NHS Foundation Trust

Leads
Professor T. Aitman
Professor Nick Cheshire
Professor Mike Pope

If you feel your NHS site would be suitable to recruit for EDS please get in contact with the EDS Study Coordinator Sofie Ashford