Overview
- DNA from 1,000 people with hEDS and 45 with HSD has been sequenced.
- Other known types of EDS and connective tissue disorders were ruled out, with only a few participants reclassified.
- No single gene explains hEDS or HSD yet. At this time, diagnosis is still based on clinical criteria, not a lab test.
Confirming hEDS diagnosis
- Out of 1,200 participants, fewer than 1% had genetic variants linked to another connective tissue condition, such as classical EDS, Marfan syndrome, or Loeys-Dietz syndrome.
- These individuals were directly contacted and guided toward appropriate follow-up care.
- For the other 99%+, the original clinical diagnosis of hEDS (or HSD) was correct showing that the 2017 criteria were used effectively by clinicians and that the HEDGE cohort is strong and reliable for genetic research.
Symptom insights – 260226 Ehlers-Danlos Society
- Most participants reported multi-system involvement.
- Common symptoms the participants reported included fatigue, digestive problems, sleep issues, and headaches.
- From the data reported by participants about the symptoms they experience, the team identified 81 main symptom groups, and more than 900 less common symptoms, providing one of the most detailed pictures of hEDS/HSD to date.
Control group comparison
- To make sense of the data, researchers compared HEDGE participants’ DNA to over 200,000 genomes from the U.S. All of Us Research Program, matching each HEDGE participant with five ancestry-matched controls.
- This confirmed that the HEDGE cohort is accurate, well-defined, and reliable for genetic discovery.
What’s Next
- Rare variant analysis: Completing studies of uncommon genetic changes that may explain subsets of hEDS.
- Genotype–phenotype studies: Exploring how genetic variants relate to symptoms, to explain why people with hEDS/HSD can have very different experiences.
- Mechanistic research: Building biological models to explain how genetic variants affect connective tissue, highlighting possible treatment targets.
- Publications: The first HEDGE papers are expected in December 2025, with more to follow in stages.
https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.63857
Bridging the Diagnostic Gap for Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders: Evidence of a Common Extracellular Matrix Fragmentation Pattern in Patient Plasma as a Potential Biomarker
Marco Ritelli, Nicola Chiarelli, Valeria Cinquina, Valeria Bertini, Silvia Piantoni, Alessia Caproli, Silvia Ebe Lucia Della Pina, Franco Franceschini, Guido Zarattini, Woodrow Gandy … See all authors
https://www.mdpi.com/2073-4409/11/24/4040
Dr Eric Ronge 