Research is making significant progress. In 2024, the Norris Lab at the Medical University of South Carolina published a preprint identifying variants in kallikrein genes (particularly KLK15) on chromosome 19 that appear to be associated with hypermobile EDS. In their study, about 32.8% of 197 hEDS patients carried at least one kallikrein variant.
Kallikrein genes encode serine proteases, enzymes that break down proteins, and may affect collagen processing, mast cell activation, and the complement system, which could help explain the wide range of symptoms seen in hEDS.
While this is an exciting advance, clinical diagnosis remains the standard of care. There is no commercially available genetic test for hEDS at this time, and having a variant of uncertain significance (VUS) on whole exome sequencing does not confirm or rule out hEDS.