Table 2.
Overview of gastrointestinal symptoms observed in studies of patients with hypermobilility spectrum disorder/hypermobile Ehlers–Danlos Syndrome (HSD/hEDS) (excluding studies in gastroenterology specialist clinics)
| Author, year | Classification utilized | Study type | Study setting and number of patients | Symptom prevalence |
|---|---|---|---|---|
| Castori et al., 2010 3 | Villefranche criteria + Brighton criteria | Observational cross‐sectional |
General genetics outpatients; Italy n = 21 (18 female) |
Reflux/heartburn (57%); dyspepsia (67%); abdominal pain (62%); constipation/diarrhea (33%); hernias (abdominal) (5%) |
| Castori et al., 2011 25 | Villefranche criteria + Brighton criteria | Observational cross‐sectional |
Multidisciplinary joint hypermobility clinic; Italy Cumulative prevalence of symptoms according to age reported—based on patient recall n = 50 (44 female) |
By age ≥ 40 years: reflux/heartburn (74%); abdominal pain (68%); chronic gastritis (48%); alternating bowel habits (72%); hernias (abdominal) (20%) |
| Mastoroudes et al., 2013 31 | Revised 1998 Brighton criteria | Observational case–control |
Hypermobility clinic; UK n = 60 HSD/hEDS; 60 age‐matched and sex‐matched controls from medical staff |
Obstructive defecation symptoms: 23% vs 5% controls (P = 0.007); straining: 62% (P < 0.001); incomplete evacuation: 63% (P < 0.001); digitation: 33% (P = 0.001); constipation: 72% (P < 0.001) |
| Zeitoun et al., 2013 28 | Villefranche criteria | Observational cross‐sectional |
EDS patient support group; France n = 134 (122 female); 108 HSD/hEDS 64% survey response rate |
Nausea (71%); reflux/heartburn (69%); dysphagia (63%); regurgitation (69%); postprandial fullness (67%); belching (71%); epigastric pain (71%); constipation (36%); IBS‐like symptoms (48%) |
| Castori et al., 2014 24 | Villefranche criteria | Observational cross‐sectional | Pedigrees were selected from two Italian outpatient clinics for EDS and inherited connective tissue disorders. 23 families with HSD/hEDS (n = 82) | Reflux/heartburn (34%); chronic gastritis (23%); abdominal pain (20%); constipation (28%) |
| Nelson et al., 2015 14 | Villefranche criteria + Brighton criteria | Observational retrospective |
Medical Genetics Clinic (1994–2013) 687 EDS patients (n = 471 HSD/hEDS) No control group included |
HSD/hEDS vs other EDS: constipation: 42% vs 29% (P = 0.02); nausea: 44% vs 37%; reflux/heartburn: 38% vs 36%; vomiting: 25% vs 22%; waterbrash: 1% vs 2%; dysphagia: 11% vs 12%; regurgitation: 4% vs 6%; postprandial fullness: 7% vs 3%; bloating: 17% vs 10%; dyspepsia: 11% vs 7%; abdominal pain: 56% vs 56%; diarrhea: 23% vs 17%; fecal urgency: 1.5% vs 2.8% |
| Fikree et al., 2017 21 | Villefranche criteria + Brighton criteria | Cross‐sectional, double‐blinded, case–control |
University students (without prior diagnosis of HSD/hEDS); UK HSD/hEDS: n = 74 (48 female) Controls: n = 88 |
HSD/hEDS vs controls: postprandial fullness: 34% vs 16% (P = 0.01); early satiety: 32% vs 17% (P = 0.03); bloating: 26% vs 23% (P = 0.59); functional dyspepsia: 39% vs 23% controls (P = 0.02); No differences in lower gastrointestinal symptoms (IBS, constipation, diarrhea, alternating bowel habit, ≤ 4 bowel motions/week). |
| Inayet et al., 2018 27 | Not specified | Observational cross‐sectional, case–control |
Cardiology and rheumatology clinics; UK 45 Marfan syndrome and 45 HSD/hEDS (33 female) 90 age‐matched and sex‐matched controls |
HSD/hEDS vs controls: functional abdominal pain: 69% vs 27% (P < 0.001); functional constipation: 73% vs 16% (P < 0.001); functional diarrhea: 47% vs 9% (P < 0.001); IBS: 33% vs 7% (P = 0.0014); functional heartburn: 47% vs 13% (P = 0.0011); functional dyspepsia: 38% vs 9% control (P = 0.029); functional bloating/distension: 31% vs 7% (P = 0.006) |
| Nee et al., 2019 23 | Not specified (Villefranche and Berlin nomenclature accepted) | Observational, cross‐sectional |
Members of local and national Marfan and EDS societies; US EDS: n = 1804 HSD/hEDS, n = 1325); MFS: n = 600); 94% female |
HSD/hEDS vs other subtypes of EDS: aerophagia: 24% vs 26% (P = 0.35); bloating: 13% 12%; heartburn: 32% vs 37% (P = 0.04); dysphagia: 29% vs 28%; IBS: 58% vs 56%; functional constipation: 8% vs 7%; diarrhea: 0.5% vs 1.3%; functional dyspepsia: 55% vs 56% |
| Alomari et al., 2020 36 | 2017 International classification of EDS | Observational retrospective |
Genetics clinic; US n = 218 (198 female) |
63% gastrointestinal symptoms at hEDS diagnosis (63%); abdominal pain (50%); nausea (50%); constipation (45%); diarrhea (38%); heartburn (36%); belching/bloating (27%); vomiting (26%); IBS‐like symptoms (22%); dysphagia (14%); fecal incontinence (6%) |
| Lam et al., 2020 5 | Not specified | Case–control |
EDS support group; UK HSD/hEDS: n = 603 Age‐matched and sex‐matched controls: n = 1994 Mean age: 39 years, 96% female 20% survey response rate |
HSD/hEDS vs control: functional dyspepsia: 57% vs 9% (P < 0.0001); IBS: 54% vs 8% (P < 0.001); functional dysphagia: 42% vs 4% (P < 0.001); rumination: 31% vs 5% (P < 0.001); functional constipation: 12% vs 10%; functional diarrhea: 5% vs 4.6%; functional anorectal disorders: 53% vs 9% (P < 0.001) |
| Tai et al., 2020 71 | Not specified | Observational cross‐sectional, case–control |
EDS support group: UK Established HSD/hEDS and hypermobility spectrum disorder: n = 616 (573 female); mean age 39 years PoTS n = 231 20% survey response |
PoTS vs non‐PoTS: functional esophageal disorders: 66% vs 50% (P < 0.001); functional heartburn: 31% vs 21% (P = 0.007); functional dysphagia: 51% vs 37% (P = 0.001); functional gastroduodenal disorders: 75% vs 67% (P = 0.04); functional dyspepsia: 68% vs 50% (P < 0.001); postprandial distress syndrome: 63% vs 42% (P < 0.001); epigastric pain syndrome: 40% vs 28% (P = 0.002); functional bowel disorders: 89% vs 91% (P = 0.5); IBS: 59% vs 51%; functional diarrhea: 3% vs 7% (P = 0.01); functional anorectal disorders: 60% vs 49% (P = 0.01) |
Villefranche criteria. 1