Approved Research

Study of the genetic basis of Hypermobile Ehlers Danlos Syndrome (hEDS) in link with cardiometabolic and cardiovascular risk traits

Lay summary

Hypermobile Ehlers Danlos Syndrome (hEDS) is a group of multiple organs disorder that varies in degree of severity with ~1 in 500 people being affected. Females are more often affected by this disease than males, and tend to present a more debilitating form. Manifestations of hEDS are the presence of several health issues, including widespread chronic pain and impairment of the autonomic nervous system that controls the function of vital organs like the heart, body temperature and digestion. The main features of hEDS consist of complications in muscles and tendons resulting from hypermobility and joint instability. It is not uncommon for patients to have multiple joint complications occurring simultaneously or experience a domino effect of existing instability impacting surrounding joints. Patients also present skin hyperextensibility and reduced dermal thickness, which increases skin fragility and difficulties of wound healing creating sometimes atrophic scarring. Recent studies showed that hEDS patients may also have fragile arteries and heart valves, which manifest through the development of cardiovascular complications such as an increased risk for tear or dissection of arteries of the heart resulting in myocardial infraction. Due to the complexity of how the disease manifest, patients may spend several years without a clear diagnosis, which may result in an important psychological distress.

One important step toward understanding hEDS is to identify genetic factors that may increase the risk of developing the disease. This step will help us understanding what are the biological impairments that result in such a wide panel of multiple health issues and providing specific treatments to patients. To achieve this goal, we have collected DNA from several families with at least one member affected by hEDS, in addition to a large cohort of patients. We believe that both rare and common genetic variants will be important to study for this disease. We plan to use the UK Biobank data to 1) identify potentially additional patients through medical records and study their DNAs in comparison to control participants; 2) perform a genetic association study using data from UK Biobank participants as controls to our cohort or patients, and 3) study the potential genetic link between hEDS and other cardiovascular and cardiometabolic diseases, aiming to understand the wide range of health issues reported in patients.