Hypermobile Ehlers–Danlos syndrome (hEDS) is one of the most common heritable connective tissue disorders. Early estimates have reported that this genetic disorder affects at least one in 5,000 individuals and more recently it has been estimated to affect upwards of 1-3% of the population worldwide. Clinically, hEDS is characterized by generalized joint hypermobility, tissue fragility including capillary fragility associated with easy bruising, poor wound healing and atrophic scarring, and skin hyper-extensibility. A particularly concerning complication of hEDS that has been underrecognized is the occurrence of fragility fractures in infancy and childhood and the social and legal consequences that can result from diagnostic errors.

Despite the clinical recognition of hEDS for decades and advances in genetic sequencing technologies, the molecular basis of hEDS has remained largely mysterious until now. Using for the first time machine learning with rigorous subject-level statistical analysis, researchers from Boston University Chobanian & Avedisian School of Medicine believe that hEDS is not a single-gene disorder, but rather involves a combination of genetic variations affecting three key biological systems. They stress that these biological associations represent baseline genetic data that prioritize hypotheses for future in-depth investigation, rather than established disease mechanisms.