Exploring cross-category relationships between symptoms in people with hypermobile EDS (hEDS) to identify disability patterns
6 affiliations
- 1ARID Lab, Department of Pediatrics, University of Arizona, Tucson, Arizona, United States of America
- 2Stephens Family Clinical Research Institute, Carle Health, Urbana, Illinois, United States of America
- 3Banner University of Arizona Medical Center, Tucson, Arizona, United States of America
- 4Department of Hematology, St. Jude Research Hospital, Memphis, Tennessee, United States of America
- 5Carle Illinois College of Medicine, University of Illinois, Urbana, Illinois, United States of America
- 6Carl R. Woese Institute for Genomic Biology, University of Illinois, Urbana, Illinois, United States of America
Abstract
Background: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder with variable symptom presentation across multiple organ systems and significant morbidity. Little is known about hEDS etiology and identifying patterns of symptom co-occurrence can reveal previously unidentified relationships between phenotypes and inform studies of underlying disease pathophysiology for symptoms that may share functional biological pathways. In this exploratory analysis, we specifically assessed the distribution of symptoms in case and controls to identify clusters of co-occurring symptoms. Methods: We have interrogated clinically relevant symptom areas in 47 females with hEDS, 36 age-matched female controls and 8 hypermobile patients without chronic pain. Studied symptoms include general health, mental health, body pain, vitality and energy, autonomic symptoms, bleeding, and gastrointestinal symptoms. We conducted hierarchal clustering on principle components (HCPC) to identify groups and compared the groups for the previously described symptoms. Radial plots were used to identify relationships between severe symptom categories. Results: Our analysis reveals statistically significantly more severe symptoms in all categories in people with hEDS compared with age- and sex-matched controls and asymptomatic hypermobile patients. HCPC identified clearly separated Low, Moderate, and High symptom groups within participants. The Low dysfunction groups include nearly all controls and hypermobile patients without chronic pain. The High dysfunction group includes ~60% of people with hEDS, while around 40% are in the Moderate dysfunction cluster. Cluster solutions for all participants were stable with moderate fit (silhouette 0.64; Jaccard boot mean 0.91). Group level radial plots showed high bleeding severity across all symptom clusters, while disproportional severity of general health, physical function, limitation of role due to physical symptoms, pain, and social functioning deficits differentiates the High from Moderate and Low Dysfunction clusters. Conclusion: Using this analysis at the group level has revealed patterns suggesting a progression of disease symptoms. People with hypermobility do not uniformly have severe symptoms but instead have some symptoms that differentiate from non-hypermobile individuals. While exploratory, using a radar multi-symptom analysis may be used to evaluate disproportionately severe symptoms contributing to the patterns of global symptom severity. These include pain but also ability to perform roles, suggesting strong utility of physical and occupational therapies to emphasize coping. This may also allow better targeting of etiological studies and may have additional utility at an individual level to develop symptom management strategies.
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BibTeX
@article{andrews2026exploring,
title = {{Exploring cross-category relationships between symptoms in people with hypermobile EDS (hEDS) to identify disability patterns}},
author = {Jennifer Andrews and Zachery Harkey and Sarah Mathena and Maureen Galindo and Sarrah Hannon and Rohith Jesudas and Christina M. Laukaitis},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0357565},
url = {https://doi.org/10.1371/journal.pone.0357565},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Exploring cross-category relationships between symptoms in people with hypermobile EDS (hEDS) to identify disability patterns
AU - Jennifer Andrews
AU - Zachery Harkey
AU - Sarah Mathena
AU - Maureen Galindo
AU - Sarrah Hannon
AU - Rohith Jesudas
AU - Christina M. Laukaitis
PY - 2026
DA - 2026/09/11
JO - PLOS One
DO - 10.1371/journal.pone.0357565
UR - https://doi.org/10.1371/journal.pone.0357565
AB - Background: Hypermobile Ehlers-Danlos Syndrome (hEDS) is a connective tissue disorder with variable symptom presentation across multiple organ systems and significant morbidity. Little is known about hEDS etiology and identifying patterns of symptom co-occurrence can reveal previously unidentified relationships between phenotypes and inform studies of underlying disease pathophysiology for symptoms that may share functional biological pathways. In this exploratory analysis, we specifically assessed the distribution of symptoms in case and controls to identify clusters of co-occurring symptoms. Methods: We have interrogated clinically relevant symptom areas in 47 females with hEDS, 36 age-matched female controls and 8 hypermobile patients without chronic pain. Studied symptoms include general health, mental health, body pain, vitality and energy, autonomic symptoms, bleeding, and gastrointestinal symptoms. We conducted hierarchal clustering on principle components (HCPC) to identify groups and compared the groups for the previously described symptoms. Radial plots were used to identify relationships between severe symptom categories. Results: Our analysis reveals statistically significantly more severe symptoms in all categories in people with hEDS compared with age- and sex-matched controls and asymptomatic hypermobile patients. HCPC identified clearly separated Low, Moderate, and High symptom groups within participants. The Low dysfunction groups include nearly all controls and hypermobile patients without chronic pain. The High dysfunction group includes ~60% of people with hEDS, while around 40% are in the Moderate dysfunction cluster. Cluster solutions for all participants were stable with moderate fit (silhouette 0.64; Jaccard boot mean 0.91). Group level radial plots showed high bleeding severity across all symptom clusters, while disproportional severity of general health, physical function, limitation of role due to physical symptoms, pain, and social functioning deficits differentiates the High from Moderate and Low Dysfunction clusters. Conclusion: Using this analysis at the group level has revealed patterns suggesting a progression of disease symptoms. People with hypermobility do not uniformly have severe symptoms but instead have some symptoms that differentiate from non-hypermobile individuals. While exploratory, using a radar multi-symptom analysis may be used to evaluate disproportionately severe symptoms contributing to the patterns of global symptom severity. These include pain but also ability to perform roles, suggesting strong utility of physical and occupational therapies to emphasize coping. This may also allow better targeting of etiological studies and may have additional utility at an individual level to develop symptom management strategies.
SN - 1932-6203
ER -