In 2018, the groundbreaking Hypermobile Ehlers Danlos Genetic Evaluation (HEDGE) was launched. Never before has there been a worldwide collaborative effort of this magnitude devoted to finding the underlying genetic markers for hypermobile EDS (hEDS). The study will also look for other blood findings that may add to our understanding of hEDS and help in the search for a diagnostic test.
Since the announcement of the extraordinary “Moonshot” donation in early 2018, which was then followed by a generous matching donation in early 2019, The Ehlers-Danlos Society brought together a highly experienced international group of physicians, geneticists, and technical volunteers to form the Hypermobile EDS Genetic Research Network, dedicated to finding the genetic cause, or causes of hEDS.
Of the 14 subtypes of the group of connective tissue disorders known collectively as the Ehlers-Danlos syndromes (EDS), only the hypermobile type does not yet have identified genetic markers.
“To find preventions and treatments for hEDS, we have to understand the cause. Genetic studies like this one provide a path towards that goal,” said Joel Hirschhorn, MD, PhD, Concordia Professor of Pediatrics and Professor of Genetics at Boston Children’s Hospital/Harvard Medical School, and a member of the Hypermobile Genetic Research Network.
Over 2019 and 2020, the HEDGE study will recruit, screen, and undertake genetic sequencing tests on 1000 individuals who have been diagnosed with hypermobile EDS by the most recent clinical criteria established in 2017.
The HEDGE study would not be possible without the EDS and Related Disorders Global Registry, another ambitious worldwide research effort spearheaded by The Ehlers-Danlos Society. Launched in July of 2018, the Global Registry is a collection of standardized health information provided by thousands of patients with all forms of EDS and hypermobility spectrum disorders (HSD), allowing researchers to compare and analyze patient data on a much larger scale than possible in individual research studies alone. The Registry has the potential to unlock countless discoveries about all forms of EDS and HSD and lays the groundwork for large-scale research efforts like the HEDGE study. All potential study participants must first join the Global Registry.
The first HEDGE enrollment event took place at The Ehlers-Danlos Society European Learning Conference in Madrid, Spain, in April 2019. Twelve in-person screening events have taken place around the world to date [July 2020], and enrolled 413 individuals with hEDS into the study: each participant has given a blood sample towards the 1000-participant goal.
Based on research and expert opinion, to date there have only been less than 200 people with hypermobile EDS who have had whole-genome sequencing, and, less than 500 who have had whole-exome sequencing with EDS around the world. To have the collection of data from this study will enable us to take giant leaps forward in research and discovery for our community. There has been an enormous amount of interest from members of our community wishing to take part in this study.
“Understanding the genetic causes of hypermobile EDS is absolutely crucial to the EDS community,” said Clair Francomano, MD, chair of The Ehlers-Danlos Society’s Medical and Scientific Board, Director of The Ehlers-Danlos Society Center for Clinical Care and Research at the Harvey Institute of Human Genetics in Baltimore, MD, and a member of the Hypermobile Genetic Research Network. “It will allow us to make unequivocal diagnoses, for one thing. Further, understanding the genetic pathways leading to hypermobile EDS will inform the search for rational therapies for this disorder, and hopefully, eventually, a cure.”
“If we are successful in identifying the underlying genes for hypermobile EDS, the opportunities for earlier diagnosis and more comprehensive treatment and care are virtually limitless,” stated Lara Bloom, President, and CEO of The Ehlers-Danlos Society. “We are incredibly grateful to the generous donors who’ve made this possible.”
This study has Institutional Review Board oversight and approval by the Genetic Alliance (IORG0003358) IRB (IRB00003999). The Genetic Alliance Federal Wide Assurance number is FWA00017292. Protocol EDS002 has been approved by the Genetic Alliance IRB (Federal registration number IORG0003358). Information can be found on this IRB by putting Genetic Alliance in the NAME search field on the Office of Human Research Protections website.