Abnormal Autonomic Physiology of Hypermobile Ehlers-Danlos Syndrome Observed in Extended Ambulatory Monitoring: A Wearable Study

Hypermobile Ehlers-Danlos Syndrome (hEDS) is a rare genetic connective tissue disorder characterized by hypermobile joints, chronic pain, fatigue, brain fog, orthostatic intolerance, and disrupted motility. It is known there is a disruption in collagen with hEDS; however, underlying pathophysiology to explain non-musculoskeletal symptomology is not known. Furthermore, palliative treatments rarely help improve the poor quality of life. The heterogeneity of the disorder further complicates the patient’s path, as time to diagnosis and treatments vary heavily on a personal basis. Here, we explore diurnal physiology from a smartwatch with the objective of continuously measuring and characterizing abnormal autonomic physiology outside an acute clinic setting over a four-week period. Patients wear a Corsano TM CardioWatch 287-2B for 30 days, continuously collecting heartrate, temperature, activity, oxygen saturation, and blood pressure. Each participant also performed symptom journaling and surveys. To date, 9 of 15 people with hEDS have completed the study and each exhibits a unique physiology profile determined by diurnal rhythms over 30 days of recording, specifically in metrics characterizing autonomic physiology: sdNN, pNN50, rmssd, skin temperature, and blood pressure. Several hEDS patients observed have distinct patterns of blood pressure and heart rate variability in their circadian rhythms that are nearly antipodal to findings expected in healthy populations. Participants exhibit more sympathetic dominance in blood pressure and heart rate variability in the supine resting state compared to their active awake state, despite reduced heart rate. When comparing states of resting (1AM-3AM) to awake (11AM-1PM) across individuals (n=9), sdNN (15.35ms), pnn50 (12.76ms), rmssd (21.82ms), and heartrate all increased (16.9bpm), and LFHF ratio decreased (-0.12). To our knowledge, this study represents the most comprehensive longitudinal analysis of autonomic physiology to date in this critically under-researched population. These preliminary findings point toward unique and distinct autonomic dysfunction in hEDS patients. We hope to leverage these findings towards an expedited hEDS inclusion in differential lists for undiagnosed patients, and toward more personalized treatment plans. This research was supported by the Ehlers-Danlos Society Research Foundation, the NIH SPARC Program (OT2 OD028183), and NIH NIGMS (T32GM148382). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.