Clinical Rheumatology

, Volume 38, Issue 2, pp 503–511 | Cite as

Prevalence and frequency of self-perceived systemic features in people with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type

  • Cliffton ChanEmail author
  • Anne Krahe
  • Yim Tang Lee
  • Leslie L. Nicholson
Original Article


Some commonly reported systemic features of joint hypermobility syndrome (JHS)/Ehlers-Danlos syndrome hypermobility type (EDS-HT) are absent from nosologies due to insufficient validity. The primary aim was to examine the hypothesised high prevalence and frequency of orthostatic intolerance, easy bruising, and urinary incontinence in adults with JHS/EDS-HT and secondarily to determine the association between extent of generalised joint hypermobility (GJH) and these systemic features. A cross-sectional cohort study was conducted via online recruitment of medically diagnosed JHS/EDS-HT patients. A survey collected demographic data and clinical history. A subgroup of participants underwent physical testing of GJH using the Beighton score and Lower Limb Assessment Score (LLAS). Descriptive analysis was performed on demographic data and self-reported non-musculoskeletal systemic features. Correlation of GJH scores and systemic features were performed using Spearman’s rank correlation. The survey was completed by 116 individuals (95% female; 16–68 years) with 57 (93% female) also participating in the physical assessment. The most prevalent systemic feature was orthostatic intolerance (98%), followed by easy bruising and urinary incontinence (97% and 84% respectively). Of those reporting symptoms of orthostatic intolerance, easy bruising, and urinary incontinence, 58%, 40%, and 18% described them as very highly frequent respectively (frequency > 75%). No significant correlations were found between the extent of systemic features and GJH scores as measured by either the Beighton score or the LLAS. The high prevalence and frequency of the systemic features found in this study, which are omitted in diagnostic classification criteria, suggest that further research on their diagnostic accuracy is warranted.


Bruising Diagnostic Gastrointestinal Hypermobility Orthostatic intolerance Urinary incontinence 



The authors would like to thank Feili Zhang and Kaitlin Meyer for their assistance in participant recruitment and data collection in this study.

Funding statement

This study was funded by a Biomedical Research Internal Grant from the Discipline of Biomedical Sciences (grant number 2015/001), Sydney Medical School, The University of Sydney.

Compliance with ethical standards

Ethical approval was granted by the University of Sydney’s Human Research Ethics Committee (No. 2012/5580).




  1. 1.
    Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A (2017) A framework for the classification of joint hypermobility and related conditions. Am J Med Genet Part C Semin Med Genet 175:148–157CrossRefGoogle Scholar
  2. 2.
    Castori M, Colombi M (2015) Generalized joint hypermobility, joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type. Am J Med Genet Part C Semin Med Genet 169:1–5CrossRefGoogle Scholar
  3. 3.
    Hakim AJ (2004) Joint hypermobility. Best Pract Res Clin Rheumatol 17:989–1004CrossRefGoogle Scholar
  4. 4.
    Grahame R, Bird HA, Child A (2000) The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS). J Rheumatol 27:1777–1779Google Scholar
  5. 5.
    Beighton P (1998) Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Am J Med Genet 77:31–37CrossRefGoogle Scholar
  6. 6.
    Tinkle BT, Bird HA, Grahame R, Lavallee M, Levy HP, Sillence D (2009) The lack of clinical distinction between the hypermobility type of Ehlers-Danlos syndrome and the joint hypermobility syndrome (a.k.a. hypermobility syndrome). Am J Med Genet A 149:2368–2370CrossRefGoogle Scholar
  7. 7.
    Castori M, Morlino S, Celletti C, Ghibellini G, Bruschini M, Grammatico P, Blundo C, Camerota F (2013) Re-writing the natural history of pain and related symptoms in the joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. Am J Med Genet A 161:2989–3004CrossRefGoogle Scholar
  8. 8.
    Hakim AJ, Sahota A (2006) Joint hypermobility and skin elasticity: the hereditary disorders of connective tissue. Clin Dermatol 24:521–533CrossRefGoogle Scholar
  9. 9.
    Castori M (2012) Ehlers-Danlos syndrome, hypermobility type: an underdiagnosed hereditary connective tissue disorder with mucocutaneous, articular, and systemic manifestations. ISRN Dermatol 2012:1–22Google Scholar
  10. 10.
    Grahame R (2009) Joint hypermobility syndrome pain. Curr Pain Headache Rep 13:427–433CrossRefGoogle Scholar
  11. 11.
    Terry RH, Palmer ST, Rimes KA, Clark CJ, Simmonds JV, Horwood JP (2015) Living with joint hypermobility syndrome: patient experiences of diagnosis, referral and self-care. Fam Pract 32:354–358CrossRefGoogle Scholar
  12. 12.
    Krahe AM, Adams RD, Nicholson LL (2017) Features that exacerbate fatigue severity in joint hypermobility syndrome/Ehlers–Danlos syndrome – hypermobility type. Disabil Rehabil 8288:1–8Google Scholar
  13. 13.
    Ross J, Grahame R (2011) Joint hypermobility syndrome. BMJ 342:275–277CrossRefGoogle Scholar
  14. 14.
    Keer R, Butler K (2010) Physiotherapy and occupational therapy in the hypermobile adult. In: Hypermobility, fibromyalgia and chronic pain. Churchill Livingstone, Edinburgh, pp 143–161CrossRefGoogle Scholar
  15. 15.
    Palmer S, Terry R, Rimes KA, Clark C, Simmonds J, Horwood J (2016) Physiotherapy management of joint hypermobility syndrome – a focus group study of patient and health professional perspectives. Physiotherapy 102:93–102CrossRefGoogle Scholar
  16. 16.
    Annemans L, Wessely S, Spaepen E, Caekelbergh K, Caubère JP, Le Lay K, Taïeb C (2008) Health economic consequences related to the diagnosis of fibromyalgia syndrome. Arthritis Rheum 58:895–902Google Scholar
  17. 17.
    Malfait F, Francomano C, Byers P, Belmont J, Berglund B, Black J, Bloom L, Bowen JM, Brady AF, Burrows NP, Castori M, Cohen H, Colombi M, Demirdas S, de Backer J, de Paepe A, Fournel-Gigleux S, Frank M, Ghali N, Giunta C, Grahame R, Hakim A, Jeunemaitre X, Johnson D, Juul-Kristensen B, Kapferer-Seebacher I, Kazkaz H, Kosho T, Lavallee ME, Levy H, Mendoza-Londono R, Pepin M, Pope FM, Reinstein E, Robert L, Rohrbach M, Sanders L, Sobey GJ, van Damme T, Vandersteen A, van Mourik C, Voermans N, Wheeldon N, Zschocke J, Tinkle B (2017) The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet Part C: Semin Med Genet 175:8–26CrossRefGoogle Scholar
  18. 18.
    Hakim AJ, Grahame R (2004) Non-musculoskeletal symptoms in joint hypermobility syndrome. Indirect evidence for autonomic dysfunction? Rheumatology 43:1194–1195CrossRefGoogle Scholar
  19. 19.
    Gazit Y, Jacob G, Grahame R (2016) Ehlers–Danlos syndrome— hypermobility type: a much neglected multisystemic disorder. Rambam Maimonides Med J 7:1–11CrossRefGoogle Scholar
  20. 20.
    Gazit Y, Nahir AM, Grahame R, Jacob G (2003) Dysautonomia in the joint hypermobility syndrome. Am J Med 115:33–40CrossRefGoogle Scholar
  21. 21.
    Rombaut L, Malfait F, Cools A, De Paepe A, Calders P (2010) Musculoskeletal complaints, physical activity and health-related quality of life among patients with the Ehlers–Danlos syndrome hypermobility type. Disabil Rehabil 32:1339–1345Google Scholar
  22. 22.
    Arunkalaivanan AS, Morrison A, Jha S, Blann A (2009) Prevalence of urinary and faecal incontinence among female members of the Hypermobility Syndrome Association (HMSA). J Obstet Gynaecol (Lahore) 29:126–128CrossRefGoogle Scholar
  23. 23.
    Lodish H, Berk A, Kaiser C, Krieger M, Scott MP, Bretscher A, Matsudaira P (2008) Molecular cell biology. WH Freeman, New YorkGoogle Scholar
  24. 24.
    Beighton P, Solomon L, Soskolne CL (1973) Articular mobility in an African population. Ann Rheum Dis 32:413–418CrossRefGoogle Scholar
  25. 25.
    Ferrari J, Parslow C, Lim E, Hayward A (2005) Joint hypermobility: the use of a new assessment tool to measure lower limb hypermobility. Clin Exp Rheumatol 23:413–420Google Scholar
  26. 26.
    Meyer K, Chan C, Hopper L, Nicholson LL (2017) Identifying lower limb specific and generalised joint hypermobility in adults: validation of the Lower Limb Assessment Score identifying lower limb specific and generalised joint hypermobility in adults : a validation study. BMC Musculoskelet Disord 18:514CrossRefGoogle Scholar
  27. 27.
    Singh H, McKay M, Baldwin JN, Nicholson LL, Chan C, Burns J, Hiller CE (2017) Beighton scores and cut-offs across the lifespan: cross-sectional study of an Australian population. Rheumatology 56:1857–1864CrossRefGoogle Scholar
  28. 28.
    Smits-Engelsman B, Klerks M, Kirby A (2011) Beighton score: a valid measure for generalized hypermobility in children. J Pediatrics 158:119–123CrossRefGoogle Scholar
  29. 29.
    Evans AM, Rome K, Peet L (2012) The foot posture index, ankle lunge test, Beighton scale and the lower limb assessment score in healthy children: a reliability study. J Foot Ankle Res 5:1CrossRefGoogle Scholar
  30. 30.
    Taylor R (1990) Interpretation of the correlation coefficient: a basic review. J Diagnostic Med Sonogr 6:35–39CrossRefGoogle Scholar
  31. 31.
    Low PA (2008) Prevalence of orthostatic hypotension. Clin Auton Res 18(SUPPL. 1):8–13CrossRefGoogle Scholar
  32. 32.
    Fu Q, Arbab-Zadeh A, Perhonen MA, Zhang R, Zuckerman JH, Levine BD (2004) Hemodynamics of orthostatic intolerance: implications for gender differences. American J Physiol Heart Circ Physiol 286:H449–H457CrossRefGoogle Scholar
  33. 33.
    Freeman R, Wieling W, Axelrod FB, Benditt DG, Benarroch E, Biaggioni I, Cheshire WP, Chelimsky T, Cortelli P, Gibbons CH, Goldstein DS, Hainsworth R, Hilz MJ, Jacob G, Kaufmann H, Jordan J, Lipsitz LA, Levine BD, Low PA, Mathias C, Raj SR, Robertson D, Sandroni P, Schatz IJ, Schondorf R, Stewart JM, van Dijk JG (2011) Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome. Autonomic Neurosci: Basic Clin 161:46–48CrossRefGoogle Scholar
  34. 34.
    Stewart JM (2013) Common syndromes of orthostatic intolerance. Pediatrics 131:968–980CrossRefGoogle Scholar
  35. 35.
    Moon J, Kim D-Y, Byun J-I, Sunwoo J-S, Lim J-A, Kim T-J, Shin JW, Lee WJ, Lee HS, Jun JS, Park KI, Jung KH, Lee ST, Jung KY, Chu K, Lee SK (2016) Orthostatic intolerance symptoms are associated with depression and diminished quality of life in patients with postural tachycardia syndrome. Health Qual Life Outcomes 14:144CrossRefGoogle Scholar
  36. 36.
    Abrams P, Smith AP, Cotterill N (2015) The impact of urinary incontinence on health-related quality of life (HRQoL) in a real-world population of women aged 45–60 years: results from a survey in France, Germany, the UK and the USA. BJU Int 115:143–152CrossRefGoogle Scholar
  37. 37.
    Bedretdinova D, Fritel X, Zins M, Ringa V (2006) The effect of urinary incontinence on health-related quality of life: is it similar in men and women? Urology 91:83–89CrossRefGoogle Scholar
  38. 38.
    Hawthorne G (2006) Measuring incontinence in Australia. Commonwealth of Australia, CanberraGoogle Scholar
  39. 39.
    McIntosh LJ, Mallett VT, Frahm JD, Richardson DA, Evans MI (1995) Gynecologic disorders in women with Ehlers-Danlos syndrome. J Soc Gynecol Investig 2:559–564CrossRefGoogle Scholar
  40. 40.
    Veit-Rubin N, Cartwright R, Singh AU, Digesu GA, Fernando R, Khullar V (2016) Association between joint hypermobility and pelvic organ prolapse in women: a systematic review and meta-analysis. Int Urogynecol J 27:1469–1478CrossRefGoogle Scholar
  41. 41.
    De Paepe A, Malfait F (2004) Bleeding and bruising in patients with Ehlers-Danlos syndrome and other collagen vascular disorders. Br J Haematol 127:491–500CrossRefGoogle Scholar
  42. 42.
    Simmons LA, Wolever RQ, Bechard EM, Snyderman R (2014) Patient engagement as a risk factor in personalized health care: a systematic review of the literature on chronic disease. Genome Med 6:16CrossRefGoogle Scholar
  43. 43.
    Stine KC, Becton DL (1997) DDAVP therapy controls bleeding in Ehlers–Danlos syndrome. J Pediatr Hematol Oncol 19:156–158CrossRefGoogle Scholar
  44. 44.
    Clinch J, Deere K, Sayers A, Palmer S, Riddoch C, Tobias JH, Clark EM (2011) Epidemiology of generalized joint laxity (hypermobility) in fourteen-year-old children from the UK: a population-based evaluation. Arthritis Rheum 63:2819–2827CrossRefGoogle Scholar
  45. 45.
    Nicholson LL, Chan C (2018) The Upper Limb Hypermobility Assessment Tool: a novel validated measure of adult joint mobility. Musculoskelet Sci Pract 35:38–45CrossRefGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2018

Authors and Affiliations

  1. 1.Discipline of Biomedical Science, School of Medical Science, Faculty of Medicine and HealthThe University of SydneySydneyAustralia
  2. 2.Discipline of Physiotherapy, Faculty of Health SciencesThe University of SydneySydneyAustralia

Personalised recommendations