Ehlers-Danlos · Connective tissue
Hypermobile Ehlers-Danlos Syndrome · hEDS
The most common EDS subtype. Diagnosis is clinical: the 2017 criteria, no confirmatory gene.
Description
Hypermobile Ehlers-Danlos syndrome is the most common subtype of Ehlers-Danlos syndrome and the only subtype in the 2017 international classification without a confirmed gene. It is a heritable connective tissue disorder. Tissues that depend on collagen, including joints, skin, and the autonomic nervous system, behave with more mechanical give than typical, and the consequences accumulate across a lifetime.
The diagnosis is clinical. The 2017 international classification, published by Malfait and colleagues in the American Journal of Medical Genetics Part C, requires three criteria, all of which must be present. Criterion 1 is generalized joint hypermobility measured by the Beighton score, with thresholds of 6 of 9 for prepubertal children, 5 of 9 for postpubertal adults to age 50, and 4 of 9 after age 50. Criterion 2 requires two of three feature sets: a set of systemic manifestations of a generalized connective tissue disorder, a positive family history with a first-degree relative meeting criteria, and musculoskeletal complications including chronic pain, recurrent dislocations, or joint instability. Criterion 3 is the exclusion of other heritable and acquired connective tissue disorders, including the genetically defined EDS subtypes, Marfan syndrome, and Loeys-Dietz syndrome.
There is no genetic test for hEDS today. When the criteria are not fully met, the workup may land on hypermobility spectrum disorder; clinical implications and management overlap.
Reported prevalence estimates range from approximately 1 in 3,100 to 1 in 5,000 when hEDS is counted alone, and substantially higher when combined with hypermobility spectrum disorder. Comorbidities frequently travel with hEDS, including postural orthostatic tachycardia syndrome, gastrointestinal dysmotility, and mast cell activation syndrome. These comorbidities sit outside the diagnostic criteria and are managed alongside hEDS.
Treatments to date
There is no FDA-approved disease-specific therapy for hEDS. Management is multidisciplinary symptom control.
Physical therapy oriented to joint stability, proprioception, and neuromuscular control is the primary intervention. Programs focused on motor control and graded loading have stronger evidence than passive stretching, which can worsen instability. Activity modification and pacing reduce flare frequency. Bracing and soft-goods support address mechanical instability at named joints, including sacroiliac belts for pelvic instability and ring splints for finger hyperextension.
Comorbidities are treated on their own tracks. POTS care includes salt and fluid loading, compression garments, and medications such as ivabradine, midodrine, fludrocortisone, or beta blockers. Gastrointestinal dysmotility is managed by motility specialists. Mast cell activation symptoms are managed with H1 and H2 antihistamines, mast cell stabilizers, and leukotriene modifiers, prescribed by allergists or immunologists familiar with the diagnosis. Pain management is multidisciplinary and prefers nonopioid strategies, including topical agents, neuropathic pain medications, and interventional approaches.
Research toward an hEDS gene is active. The Norris Lab at the Medical University of South Carolina runs the largest public gene-discovery effort. A confirmed genetic finding would change the diagnostic framework and open a path to subtype-specific therapy.