Tulane University researchers have discovered a possible genetic cause for hypermobility (commonly called double-jointedness) and a range of associated connective tissue disorders such as hypermobile Ehlers-Danlos syndrome, according to preliminary findings published in the journal Heliyon.
You may know someone with overly flexible joints, a friend or family member who can easily slide into a split or bend limbs to impossible angles. But hypermobility is a more serious condition than being “double-jointed.”
For those with hypermobile Ehlers-Danlos syndrome (EDS), the same conditions that create fragile connective tissue can cause a range of symptoms that, on the surface, can seem unrelated: physical conditions such as joint pain, chronic fatigue, thin tooth enamel, dizziness, digestive trouble and migraines; and psychiatric disorders, such as anxiety and depression. Women with hypermobile EDS may also be at increased risk for endometriosis or uterine fibroids.
For years, researchers have struggled to find the cause of hypermobility and hypermobile EDS. Of the 13 subtypes of EDS, hypermobile EDS comprises more than 90% of the cases. But until this study, hypermobile EDS was the only subtype without a known genetic correlate. As a result, symptoms have often been treated individually rather than as the result of a single cause.
Researchers at Tulane University School of Medicine have linked hypermobility to a deficiency of folate – the natural form of vitamin B9 – caused by a variation of the MTHFR gene.
“You’ve got millions of people that likely have this, and until now, there’s been no known cause we’ve known to treat,” said Gregory Bix, MD, dector of the Tulane University Clinical Neuroscience Research Center. “It’s a big deal.”
Those with this genetic variant can’t metabolize folate, which causes unmetabolized folate to accumulate in the bloodstream. The folate deficiency may prevent key proteins from binding collagen to the extracellular matrix. This results in more elastic connective tissue, hypermobility, and a potential cascade of associated conditions.
The discovery could help doctors more accurately diagnose hypermobility and hypermobile EDS by looking for elevated folate levels in blood tests and the MTHFR genetic variant.
“Hypermobility is widespread and unfortunately under-recognized,” said Dr. Jacques Courseault, medical director of the Tulane Fascia Institute and Treatment Center. “I’m excited about being able to treat the masses where people aren’t going their whole lives being frustrated and not getting the treatment they need."
Doctors discovered the connection between folate deficiency and the MTHFR gene by working with patients at Tulane’s Hypermobility and Ehlers-Danlos Clinic, the only such clinic in the U.S. that focuses on fascia disorders. Blood tests of hypermobile patients who showed signs of associated medical conditions revealed elevated levels of unmetabolized folate. Subsequent tests showed that most of those with elevated folate serum levels had the genetic polymorphism.
The good news is a treatment already exists. Methylated folate – folate that is already processed – is FDA-approved and widely available.
Though Courseault said more lab research and clinical testing needs to be done, patients who have been treated with folate have shown improvement: less pain, less brain fog, fewer allergies and improved gastrointestinal function.
“We’ve discovered something in medicine that can help, not a small group of people, but potentially many across the world,” Courseault said. “This is real, it’s been vetted out well and clinically we’re noticing a difference.”
Pictured here is Tulane University Researcher Jacques Courseault, testing a patient for hypermobility. Courseault and colleague Gregory Bix, MD, have found a possible genetic cause for hypermobility and hypermobile Ehlers-Danlos syndrome.