Prevalence of Functional GI Diseases and Pelvic Floor Symptoms in Marfan Syndrome and Ehlers-Danlos Syndrome: A National Cohort Study
Open accessAbstract
Background and Aims: Prior studies have shown a high prevalence of gastrointestinal (GI) symptoms, diagnoses of functional GI diseases (FGIDs), and pelvic floor symptoms associated with Ehlers-Danlos syndrome (EDS). It is unclear if Marfan syndrome (MFS), another common hereditary noninflammatory connective tissue disorder, is also associated these symptoms. This study evaluates the prevalence of and compares FGIDs and pelvic floor symptoms in a national cohort of EDS and MFS patients. Methods: A questionnaire was sent to members of local and national MFS and EDS societies. The questionnaire evaluated the presence of GI and pelvic floor symptoms and diagnoses. The presence of FGIDs was confirmed using Rome III criteria. Quality of life was evaluated and scored with the CDC quality of life. Key Results: Overall, 3934 patients completed the questionnaire, from which 1804 reported that they had some form of EDS and 600 had MFS. In total, 93% of patients with EDS complained of GI symptoms and qualified for at least one FGID compared with 69.8% of patients with MFS. When comparing EDS prevalence of upper and lower GI symptoms as well as FGIDs, subjects with EDS reported significantly higher prevalence of Rome III FGIDs as compared with those with MFS. Irritable bowel syndrome (57.8% vs. 27.0%, P<0.001), functional dyspepsia (FD) (55.4% vs. 25.0%, P<0.001), postprandial distress (49.6% vs. 21.7%, P<0.001), heartburn (33.1% vs. 16.8%, P<0.001), dysphagia (28.5% vs. 18.3%, P<0.001), aerophagia (24.7% vs. 12.3%, P<0.001), and nausea (24.7% vs. 7.2%, P<0.001) were all significantly greater in the EDS population compared with MFS population. The prevalence of FGIDs was similar across subtypes of EDS. In general, participants with EDS were more likely to have nearly all pelvic floor symptoms as compared with participants with MFS. Conclusions: The prevalence of FGIDs and pelvic floor symptoms in EDS is higher than that found in MFS. The prevalence of FGIDs were similar across EDS subtypes. This study supports the mounting evidence for FGIDs in those with connective tissue diseases, but more specifically, in EDS.
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In the subgroup of four studies, the prevalence of functional heartburn in patients with hEDS/HSD was 29.9% (95% CI 23.9-36.8).
“functional heartburn (29.9%, 95% CI 23.9–36.8)”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Methods (Study Questions and Definitions; page unavailable) explicitly distinguish reported heartburn symptoms from a diagnosis of functional heartburn, which the survey could not establish. The Results (Prevalence of Functional Gastrointestinal Disorders; page unavailable) give heartburn prevalence as 33.1% in EDS participants. This single-cohort paper does not report a four-study pooled estimate of 29.9% or the stated confidence interval. (LLM, conf=0.88)
Checked by a reasoning model — may be wrong.
Experimental — accuracy not yet measuredIn the subgroup of four studies, the prevalence of functional dyspepsia in patients with hEDS/HSD was 55.4% (95% CI 52.5-58.3).
“functional dyspepsia was the most prevalent DGBI, reported in 55.4% (95% CI 52.5–58.3) of patients with hEDS/HSD”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Results (Prevalence of Functional Gastrointestinal Disorders; page unavailable) report functional dyspepsia in 55.4% of the EDS group. They do not report a four-study pooled estimate or the stated confidence interval, and the figure is for EDS overall rather than specifically hEDS/HSD. IBS was more prevalent in this cohort (57.8%), so the paper also does not support calling functional dyspepsia the most prevalent disorder. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn the subgroup of four studies, the prevalence of functional dysphagia in patients with hEDS/HSD was 34.2% (95% CI 25.7-43.8).
“functional dysphagia (34.2%, 95% CI 25.7–43.8)”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Results section (page unavailable) reports dysphagia in 28.5% of the EDS cohort and says functional GI disorder prevalence was similar across EDS subtypes. It does not report a pooled estimate from four studies, a 34.2% prevalence for hEDS/HSD, or the stated confidence interval. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn the subgroup of four studies, the prevalence of nausea and vomiting disorders in patients with hEDS/HSD was 14.4% (95% CI 8.6-23.2).
“nausea and vomiting disorders (14.4%, 95% CI 8.6–23.2)”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Results (page unavailable) report nausea in 24.7% and cyclical vomiting syndrome in 20.6% of the EDS group. The paper does not report a pooled estimate from four studies, the stated 14.4% prevalence or its 95% confidence interval for patients with hEDS/HSD. (LLM, conf=0.86)
Experimental — accuracy not yet measuredIn the subgroup of four studies, the prevalence of IBS in patients with hEDS/HSD was 54.0% (95% CI 49.5-58.4).
“followed by IBS (54.0%, 95% CI 49.5–58.4)”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Results (Prevalence of Functional Gastrointestinal Disorders; page unavailable) report that IBS affected 57.8% of the surveyed EDS group, supporting a high IBS prevalence. The paper reports a single cohort, not a subgroup analysis of four studies, and does not give the claimed 54.0% estimate or 95% confidence interval for hEDS/HSD. (LLM, conf=0.86)
Experimental — accuracy not yet measured
In the subgroup of four studies, the prevalence of functional bloating in patients with hEDS/HSD was 7.8% (95% CI 2.8-19.9).
“functional bloating (7.8%, 95% CI 2.8–19.9)”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Results section (‘FGIDs in EDS compared to MFS’; page unavailable) reports bloating in 12.4% of the EDS group, so the paper addresses bloating prevalence in EDS. It is a single cohort study, however, and does not report a pooled estimate from four studies, a 7.8% prevalence, or the stated confidence interval for hEDS/HSD. (LLM, conf=0.82)
Experimental — accuracy not yet measuredIn the subgroup of four studies, the prevalence of functional chest pain in patients with hEDS/HSD was 7.6% (95% CI 3.0-17.7).
“functional chest pain (7.6%, 95% CI 3.0–17.7)”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Results section reports prevalence estimates for EDS symptoms including heartburn and dysphagia, but does not report functional chest pain. Searches for functional chest pain and the figures 7.6%, 3.0%, and 17.7% found no four-study estimate or confidence interval in our copy. Page numbers were not available. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn the subgroup of four studies, the prevalence of belching disorders in patients with hEDS/HSD was 15.2% (95% CI 8.8-25.0).
“belching disorders (15.2%, 95% CI 8.8–25.0)”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Results section reports aerophagia in 24.7% of surveyed EDS participants, but does not report the prevalence of belching disorders. Searches for the 15.2% estimate, its 95% confidence interval, and a four-study hEDS/HSD subgroup found no matching passage in our copy; no page number was available. (LLM, conf=0.76)
Experimental — accuracy not yet measuredIn the subgroup of four studies, the prevalence of globus in patients with hEDS/HSD was 2.1% (95% CI 1.7-2.7).
“globus (2.1%, 95% CI 1.7–2.7)”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Results section reports GI symptom prevalence from a single EDS and Marfan syndrome questionnaire study, not a pooled estimate from four studies. A search of our copy for globus and the stated 2.1% prevalence with its confidence interval found no passage addressing that estimate; page numbers were unavailable. (LLM, conf=0.75)
Experimental — accuracy not yet measuredIn the subgroup of four studies, the prevalence of functional constipation in patients with hEDS/HSD was 19.3% (95% CI 10.3-33.1).
“functional constipation (19.3%, 95% CI 10.3–33.1)”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Results section reports 13.4% for IBS with constipation in the EDS group, but does not report a functional-constipation prevalence. Searches for functional constipation, 19.3%, the confidence interval, and a four-study subgroup found no matching analysis in our copy. Page numbers were not available. (LLM, conf=0.75)
Experimental — accuracy not yet measuredIn the subgroup of four studies, the prevalence of rumination in patients with hEDS/HSD was 14.1% (95% CI 8.6-23.2).
“rumination (14.1%, 95% CI 8.6–23.2)”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Results section reports GI disorder prevalence in a single EDS cohort, but does not report rumination prevalence or a pooled estimate from four studies. Searches for “rumination” and the stated prevalence and confidence interval found no supporting passage in our copy; page numbers were not available. (LLM, conf=0.77)
Experimental — accuracy not yet measuredIn the subgroup of four studies, the prevalence of functional diarrhoea in patients with hEDS/HSD was 5% (95% CI 1.6-14.8).
“functional diarrhoea (5%, 95% CI 1.6–14.8)”
From Meta-Analysis: Chronic Gastrointestinal Symptoms and Comorbidities in Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders (2026) · cites this paper as [32]
The Results section reports IBS-diarrhea in 11.8% of respondents with EDS, but does not report a prevalence of functional diarrhoea. Searches for the 5% estimate, its 95% confidence interval, and a four-study subgroup found no matching passage in our copy; this paper describes a single cohort rather than a pooled estimate. Page numbers were not available in the indexed passages. (LLM, conf=0.76)
Experimental — accuracy not yet measuredThe reported prevalence of gastrointestinal symptoms varies widely depending on whether it is derived from population-based studies, support groups, non-gastroenterological specialist clinics, or gastroenterology clinics.
“Moreover, the reported prevalence of gastrointestinal symptoms varies widely depending on whether it is derived from population‐based studies, support groups, non‐gastroenterological specialist (genetics, cardiology and rheumatology) clinics (Table 2) and gastroenterology clinics (Table 3).”
From Hypermobile Ehlers–Danlos syndrome and disorders of the gastrointestinal tract: What the gastroenterologist needs to know (2022) · cites this paper as [23]
A relationship between autonomic dysfunction and mast cell activation syndrome disorders has been observed in HSD/hEDS and suggested to cause or aggravate some of the symptoms reported.
“A relationship between autonomic dysfunction and mast cell activation syndrome disorders has also been observed in HSD/hEDS and suggested to cause or aggravate some of the symptoms reported. 11,12”
From Rome IV Functional Gastrointestinal Disorders and Health Impairment in Subjects With Hypermobility Spectrum Disorders or Hypermobile Ehlers-Danlos Syndrome (2021) · cites this paper as [12]
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- Authors
- Nee, J., Kilaru, S., Kelley, J., Oza, S. S., Hirsch, W., Ballou, S., Lembo, A., & Wolf, J.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Endicott College (US)
- Corresponding author
- Nee, Judy
- Kilaru, Saikiran
- Oza, Sveta S.
- Hirsch, William
- Ballou, Sarah
- Lembo, Anthony
- Wolf, Jacqueline
- Venue
- Journal of Clinical Gastroenterology
- Published
- 2019-10
- Volume
- 53
- Issue
- 9
- Pages
- 653-659
- ISSN
- 0192-0790 (ISSN-L)
- PMC
- PMC6642856
- OpenAlex
- W2914983238
- Cited by
- 29
- References
- 23
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 8 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 4
- FWCI
- 2.28
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Gastroenterology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (T32DK007760)
- National Center for Complementary and Integrative Health (R01AT008573)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Health Sciences › Medicine › Rheumatology › Pelvic floor disorders treatments
- Keywords
- functional gastrointestinal disorders, Ehlers-Danlos syndrome, Marfan syndrome, pelvic floor symptoms, connective tissue diseases, irritable bowel syndrome, functional dyspepsia, postprandial distress, dysphagia, aerophagia, heartburn, quality of life, Rome III criteria, prevalence, hereditary connective tissue disorders
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Ehlers-Danlos Syndrome, Female, Gastrointestinal Diseases, Humans, Male, Marfan Syndrome, Middle Aged, Quality of Life, Surveys and Questionnaires, Cohort Studies, Prevalence, Young Adult, Pelvic Floor Disorders
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