Comorbidities and systemic features
Conditions that often come with EDS: dysautonomia and POTS, mast cell activation, digestive problems, pain, and fatigue.
The “trifecta”: hEDS, POTS, and mast cell activation reported together
patient-reported patternevidence: community signalindependent evidence agreesPatient communities often describe hEDS, POTS (a form of dysautonomia), and mast cell activation syndrome (MCAS) occurring together, and call the combination the “trifecta”. In a Global Registry survey of 505 people with hEDS, POTS and MCAS were among the diagnoses participants most often endorsed as accurate. Whether the three share a mechanism is unknown.
The hEDS criteria in the 2017 classification count signs of a more generalized connective tissue disorder, such as soft skin, hernias, pelvic floor prolapse, mitral valve prolapse, and aortic root dilatation. Chronic musculoskeletal pain counts toward the criteria as a musculoskeletal complication (Feature C), but digestive, autonomic, and fatigue problems are not diagnostic criteria. Papers published alongside the classification describe them: Tinkle and colleagues review the symptoms and disorders reported with hEDS, and Chopra and colleagues review chronic pain in EDS.
In a registry survey, people with hEDS reported about ten other diagnoses
findingevidence: probableindependent evidence agreesA Global Registry survey of 505 people with clinically confirmed hEDS, published in 2023, found an average of 10.45 other diagnoses. Anxiety, depression, and migraine were the most common. Participants most often rejected functional neurological disorder, multiple sclerosis, and fibromyalgia as wrong, and most often endorsed POTS, cervical instability, and MCAS as accurate.
Craniocervical instability and tethered cord in hEDS: contested
findingevidence: contestedindependent evidence agreesCraniocervical instability (CCI) and tethered cord come up often in patient communities, and cervical instability was one of the diagnoses participants most often endorsed as accurate in a Global Registry survey of people with hEDS. Controlled evidence is limited, and surgery for these conditions carries real risk.
The 2017 series and subsequent cohort work document gastrointestinal dysmotility (reflux, gastroparesis, constipation) and autonomic dysfunction (orthostatic intolerance, POTS) as leading comorbidity domains in hEDS/HSD. In a 2025 survey at a German EDS clinic, musculoskeletal pain and joint instability were the most common first symptoms.