Hypermobile Ehlers-Danlos Syndrome and Hypermobility Spectrum Disorders

 

Am Fam Physician. 2021 Apr 15;103(8):481-492.

  Patient information: See related handout on hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorder, written by the authors of this article.

Author disclosure: No relevant financial affiliations.

Hypermobile Ehlers-Danlos syndrome (EDS) and hypermobility spectrum disorders are the most common symptomatic joint hypermobility conditions seen in clinical practice. The 2017 International Classification of the Ehlers-Danlos syndromes replaced previous terms for symptomatic joint hypermobility with hypermobile EDS and introduced the term hypermobility spectrum disorders for patients not meeting diagnostic criteria for hypermobile EDS. Both are diagnosed by applying the 2017 diagnostic criteria, which also excludes other less common conditions presenting with joint hypermobility such as other forms of EDS and heritable connective tissue disorders. Hypermobile EDS is inherited in an autosomal dominant pattern, but it does not have a known genetic mutation to help with diagnosis. Clinical features of hypermobile EDS include joint hypermobility, skin findings, and joint pains or recurrent dislocations. Hypermobile EDS and, less commonly, hypermobility spectrum disorders may also be associated with several extra-articular symptoms, including anxiety disorders, chronic pain, fatigue, orthostatic intolerance, functional gastrointestinal disorders, and pelvic and bladder dysfunction. The central goals of therapy are managing symptoms, preventing joint injury, and educating patients about their condition. Based on limited evidence, patients with hypermobile EDS/hypermobility spectrum disorders may benefit from physical and occupational therapy, psychological support, and self-management. Primary care physicians play a key role not only in initial recognition, diagnosis, and patient education, but by virtue of their ongoing relationship they can also help oversee and coordinate the multidisciplinary team many of these patients require.

Hypermobile Ehlers-Danlos syndrome (EDS) and hypermobility spectrum disorders are the most common symptomatic joint hypermobility conditions seen in clinical practice.1,2 Family physicians play a vital role in the care of patients with these conditions, from initial diagnosis to ongoing care.

WHAT'S NEW ON THIS TOPIC

Hypermobility Spectrum Disorders

The 2017 International Classification of the Ehlers-Danlos syndromes replaced prior terms for symptomatic joint hypermobility with hypermobile Ehlers-Danlos syndrome and introduced the term hypermobility spectrum disorder for patients not meeting hypermobile Ehlers-Danlos syndrome diagnostic criteria.

A 2013 U.K. population survey found that 3.4% of adults endorsed hypermobility and chronic widespread pain using validated instruments.

Generalized joint hypermobility is more common than hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders because patients with generalized joint hypermobility may be asymptomatic. When assessed in student population samples using the 2017 criteria, 4% to 11% of children three to 19 years of age had generalized joint hypermobility.

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SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingComments

Suspect hypermobile EDS/hypermobility spectrum disorders in patients with joint hypermobility and associated symptoms such as joint pain or dislocations and typical skin findings, arthralgias, recurrent hernias, marfanoid habitus, or family history of EDS.1

C

Expert opinion from 2017 International Classification of the Ehlers-Danlos syndromes

Assess joint hypermobility in patients suspected of having hypermobile EDS/hypermobility spectrum disorders with a Beighton score and a validated five-part questionnaire.1,41,43

C

Disease-oriented outcomes and expert opinion

Early multidisciplinary treatment that includes physical, occupational, and cognitive behavior therapy; orthotics; and community and specialty support may optimize outcomes in patients with joint hypermobility symptoms.4648,58,59

C

Expert opinion and several case series studies


EDS = Ehlers-Danlos syndrome.

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to https://www.aafp.org/afpsort.

The Authors

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KENNETH S. YEW, MD, MPH, is a faculty member at the Gundersen Medical Foundation Family Medicine Residency, La Crosse, Wis. He is also a clinical adjunct assistant professor in the Department of Family Medicine at the Uniformed Services University of the Health Sciences, Bethesda, Md....

KARA A. KAMPS-SCHMITT, MD, is a family physician at the Gundersen Clinic, Tomah, Wis.

ROBYN BORGE, MD, is the associate program director and a founding member of the Gundersen Medical Foundation Family Medicine Residency.

Address correspondence to Kenneth S. Yew, MD, MPH, Gundersen Family Medicine Residency Clinic, 1900 South Ave., Mailstop FB2-009, La Crosse, WI 54601 (email: kenyew63@gmail.com). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.

References

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1. Malfait F, Francomano C, Byers P, et al. The 2017 International Classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):8–26....

2. Tinkle B, Castori M, Berglund B, et al. Hypermobile Ehlers-Danlos syndrome (a.k.a. Ehlers-Danlos syndrome Type III and Ehlers-Danlos syndrome hypermobility type): clinical description and natural history. Am J Med Genet C Semin Med Genet. 2017;175(1):48–69.

3. National Center for Advancing Translational Sciences; Genetic and Rare Diseases Information Center (GARD). Ehlers-Danlos syndromes. Updated April 20, 2017. Accessed May 22, 2020. https://rarediseases.info.nih.gov/diseases/6322/ehlers-danlos-syndromes

4. Castori M, Tinkle B, Levy H, et al. A framework for the classification of joint hypermobility and related conditions. Am J Med Genet C Semin Med Genet. 2017;175(1):148–157.

5. The Ehlers-Danlos Society. Hypermobile Ehlers-Danlos syndrome (hEDS) vs. hypermobility spectrum disorders (HSD): what's the difference? Accessed June 18, 2020. https://ehlers-danlos.com/wp-content/uploads/hEDSvHSD.pdf

6. The International Consortium on Ehlers-Danlos Syndromes & Related Disorders in association with the Ehlers-Danlos Society. Diagnostic criteria for hypermobile Ehlers-Danlos syndrome (hEDS). Accessed March 2, 2020. https://www.ehlers-danlos.com/wp-content/uploads/hEDS-Dx-Criteria-checklist-1.pdf

7. Hakim AJ, Grahame R. A simple questionnaire to detect hypermobility: an adjunct to the assessment of patients with diffuse musculoskeletal pain. Int J Clin Pract. 2003;57(3):163–166.

8. McGillis L, Mittal N, Santa Mina D, et al. Utilization of the 2017 diagnostic criteria for hEDS by the Toronto GoodHope Ehlers-Danlos syndrome clinic: a retrospective review. Am J Med Genet A. 2020;182(3):484–492.

9. Cederlöf M, Larsson H, Lichtenstein P, et al. Nationwide population-based cohort study of psychiatric disorders in individuals with Ehlers-Danlos syndrome or hypermobility syndrome and their siblings. BMC Psychiatry. 2016;16:207.

10. Demmler JC, Atkinson MD, Reinhold EJ, et al. Diagnosed prevalence of Ehlers-Danlos syndrome and hypermobility spectrum disorder in Wales, UK: a national electronic cohort study and case-control comparison. BMJ Open. 2019;9(11):e031365.

11. Mulvey MR, Macfarlane GJ, Beasley M, et al. Modest association of joint hypermobility with disabling and limiting musculoskeletal pain: results from a large-scale general population-based survey. Arthritis Care Res (Hoboken). 2013;65(8):1325–1333.

12. Barçak ÖF, Karkucak M, Çapkin E, et al. Prevalence of generalized joint hypermobility and fibromyalgia syndrome in the children population of Trabzon: a Turkish study. Turk J Phys Med Rehab. 2015;61:6–11.

13. Gocentas A, Jascaniniene N, Pasek M, et al. Prevalence of generalised joint hypermobility in school-aged children from east-central European region. Folia Morphol (Warsz). 2016;75(1):48–52.

14. Mikkelsson M, Salminen JJ, Kautiainen H. Joint hypermobility is not a contributing factor to musculoskeletal pain in pre-adolescents. J Rheumatol. 1996;23(11):1963–1967.

15. Remvig L, Kümmel C, Kristensen JH, et al. Prevalence of generalized joint hypermobility, arthralgia and motor competence in 10-year-old school children. Int Musculoskelet Med. 2011;33(4):137–145.

16. Seçkin U, Tur BS, Yilmaz O, et al. The prevalence of joint hypermobility among high school students. Rheumatol Int. 2005;25(4):260–263.

17. Singh H, McKay M, Baldwin J, et al. Beighton scores and cut-offs across the lifespan: cross-sectional study of an Australian population. Rheumatology (Oxford). 2017;56(11):1857–1864.

18. Rombaut L, Malfait F, De Wandele I, et al. Muscle-tendon tissue properties in the hypermobility type of Ehlers-Danlos syndrome. Arthritis Care Res (Hoboken). 2012;64(5):766–772.

19. Smith TO, Jerman E, Easton V, et al. Do people with benign joint hypermobility syndrome (BJHS) have reduced joint proprioception? A systematic review and meta-analysis. Rheumatol Int. 2013;33(11):2709–2716.

20. Chiarelli N, Carini G, Zoppi N, et al. Transcriptome-wide expression profiling in skin fibroblasts of patients with joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type. PLoS One. 2016;11(8):e0161347.

21. Colombi M, Dordoni C, Chiarelli N, et al. Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type compared to other heritable connective tissue disorders. Am J Med Genet C Semin Med Genet. 2015;169C(1):6–22.

22. Botrus G, Baker O, Borrego E, et al. Spectrum of gastrointestinal manifestations in joint hypermobility syndromes. Am J Med Sci. 2018;355(6):573–580.

23. Bulbena A, Baeza-Velasco C, Bulbena-Cabré A, et al. Psychiatric and psychological aspects in the Ehlers-Danlos syndromes [published correction appears in Am J Med Genet A. 2017;173(12):3241]. Am J Med Genet C Semin Med Genet. 2017;175(1):237–245.

24. De Wandele I, Rombaut L, Malfait F, et al. Clinical heterogeneity in patients with the hypermobility type of Ehlers-Danlos syndrome. Res Dev Disabil. 2013;34(3):873–881.

25. Fikree A, Chelimsky G, Collins H, et al. Gastrointestinal involvement in the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175(1):181–187.

26. Hugon-Rodin J, Lebègue G, Becourt S, et al. Gynecologic symptoms and the influence on reproductive life in 386 women with hypermobility type Ehlers-Danlos syndrome: a cohort study. Orphanet J Rare Dis. 2016;11(1):124.

27. De Wandele I, Rombaut L, De Backer T, et al. Orthostatic intolerance and fatigue in the hypermobility type of Ehlers-Danlos syndrome. Rheumatology (Oxford). 2016;55(8):1412–1420.

28. Hakim A, O'Callaghan C, De Wandele I, et al. Cardiovascular autonomic dysfunction in Ehlers-Danlos syndrome—Hypermobile type. Am J Med Genet C Semin Med Genet. 2017;175(1):168–174.

29. Atzinger CL, Meyer RA, Khoury PR, et al. Cross-sectional and longitudinal assessment of aortic root dilation and valvular anomalies in hypermobile and classic Ehlers-Danlos syndrome. J Pediatr. 2011;158(5):826–830.e1.

30. Mastoroudes H, Giarenis I, Cardozo L, et al. Lower urinary tract symptoms in women with benign joint hypermobility syndrome: a case-control study. Int Urogynecol J. 2013;24(9):1553–1558.

31. Castori M, Dordoni C, Morlino S, et al. Spectrum of mucocutaneous manifestations in 277 patients with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. Am J Med Genet C Semin Med Genet. 2015;169C(1):43–53.

32. Zhou Z, Rewari A, Shanthanna H. Management of chronic pain in Ehlers-Danlos syndrome: two case reports and a review of literature. Medicine (Baltimore). 2018;97(45):e13115.

33. Albayrak İ, Yilmaz H, Akkurt HE, et al. Is pain the only symptom in patients with benign joint hypermobility syndrome? Clin Rheumatol. 2015;34(9):1613–1619.

34. Grahame R. Joint hypermobility syndrome pain. Curr Pain Headache Rep. 2009;13(6):427–433.

35. Rombaut L, Scheper M, De Wandele I, et al. Chronic pain in patients with the hypermobility type of Ehlers-Danlos syndrome: evidence for generalized hyperalgesia. Clin Rheumatol. 2015;34(6):1121–1129.

36. Gharbiya M, Moramarco A, Castori M, et al. Ocular features in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type: a clinical and in vivo confocal microscopy study. Am J Ophthalmol. 2012;154(3):593–600.e1.

37. Baeza-Velasco C, Bulbena A, Polanco-Carrasco R, et al. Cognitive, emotional, and behavioral considerations for chronic pain management in the Ehlers-Danlos syndrome hypermobility-type: a narrative review. Disabil Rehabil. 2019;41(9):1110–1118.

38. Hakim A, De Wandele I, O'Callaghan C, et al. Chronic fatigue in Ehlers-Danlos syndrome—Hypermobile type. Am J Med Genet C Semin Med Genet. 2017;175(1):175–180.

39. Grahame R. Hypermobility: overmedicalized? A debate. First opposition: I10. In: Williams D. Reproductive issues in rheumatology: do you know how to advise your patients? Rheumatology. 2012;51(suppl 3):iii1–iii6.

40. Castori M, Hakim A. Contemporary approach to joint hypermobility and related disorders. Curr Opin Pediatr. 2017;29(6):640–649.

41. Juul-Kristensen B, Schmedling K, Rombaut L, et al. Measurement properties of clinical assessment methods for classifying generalized joint hypermobility—a systematic review. Am J Med Genet C Semin Med Genet. 2017;175(1):116–147.

42. Urban Z; National Organization for Rare Disorders (NORD). Cutis laxa. Updated 2014. Accessed March 3, 2020. https://rarediseases.org/rare-diseases/cutis-laxa/

43. Smits-Engelsman B, Klerks M, Kirby A. Beighton score: a valid measure for generalized hypermobility in children. J Pediatr. 2011;158(1):119–123, 123.e1–123.e4.

44. Beighton P, Solomon L, Soskolne CL. Articular mobility in an African population. Ann Rheum Dis. 1973;32(5):413–418.

45. Bale P, Easton V, Bacon H, et al. The effectiveness of a multidisciplinary intervention strategy for the treatment of symptomatic joint hypermobility in childhood: a randomised, single Centre parallel group trial (The Bendy Study). Pediatr Rheumatol Online J. 2019;17(1):2.

46. Engelbert RHH, Juul-Kristensen B, Pacey V, et al. The evidence-based rationale for physical therapy treatment of children, adolescents, and adults diagnosed with joint hypermobility syndrome/hypermobile Ehlers Danlos syndrome. Am J Med Genet C Semin Med Genet. 2017;175(1):158–167.

47. Russek LN, Stott P, Simmonds J. Recognizing and effectively managing hypermobility-related conditions. Phys Ther. 2019;99(9):1189–1200.

48. Smith TO, Bacon H, Jerman E, et al. Physiotherapy and occupational therapy interventions for people with benign joint hypermobility syndrome: a systematic review of clinical trials. Disabil Rehabil. 2014;36(10):797–803.

49. Castori M, Morlino S, Celletti C, et al. 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. 2013;161A(12):2989–3004.

50. Tinkle BT, Levy HP. Symptomatic joint hypermobility: the hypermobile type of Ehlers-Danlos syndrome and the hypermobility spectrum disorders. Med Clin North Am. 2019;103(6):1021–1033.

51. Russek LN, LaShomb EA, Ware AM, et al. United States physical therapists' knowledge about joint hypermobility syndrome compared with fibromyalgia and rheumatoid arthritis. Physiother Res Int. 2016;21(1):22–35.

52. Huston P, McFarlane B. Health benefits of tai chi: what is the evidence? Can Fam Physician. 2016;62(11):881–890.

53. Bennett SE, Walsh N, Moss T, et al. Understanding the psychosocial impact of joint hypermobility syndrome and Ehlers-Danlos syndrome hypermobility type: a qualitative interview study. Disabil Rehabil. 2019;1–10.

54. Palmer S, Bridgeman K, Di Pierro I, et al. The views of people with joint hypermobility syndrome on its impact, management and the use of patient-reported outcome measures. A thematic analysis of open-ended questionnaire responses. Musculoskeletal Care. 2019;17(2):183–193.

55. Terry RH, Palmer ST, Rimes KA, et al. Living with joint hypermobility syndrome: patient experiences of diagnosis, referral and self-care. Fam Pract. 2015;32(3):354–358.

56. Berglund B, Mattiasson AC, Randers I. Dignity not fully upheld when seeking health care: experiences expressed by individuals suffering from Ehlers-Danlos syndrome. Disabil Rehabil. 2010;32(1):1–7.

57. Wiesmann T, Castori M, Malfait F, et al. Recommendations for anesthesia and perioperative management in patients with Ehlers-Danlos syndrome(s). Orphanet J Rare Dis. 2014;9:109.

58. Bathen T, Hångmann AB, Hoff M, et al. Multidisciplinary treatment of disability in Ehlers-Danlos syndrome hypermobility type/hypermobility syndrome: a pilot study using a combination of physical and cognitive-behavioral therapy on 12 women. Am J Med Genet A. 2013;161A(12):3005–3011.

59. Rahman A, Daniel C, Grahame R. Efficacy of an outpatient pain management programme for people with joint hypermobility syndrome. Clin Rheumatol. 2014;33(11):1665–1669.

60. Scheper MC, Nicholson LL, Adams RD, et al. The natural history of children with joint hypermobility syndrome and Ehlers-Danlos hypermobility type: a longitudinal cohort study. Rheumatology (Oxford). 2017;56(12):2073–2083.

61. Pacey V, Tofts L, Adams RD, et al. Quality of life prediction in children with joint hypermobility syndrome. J Paediatr Child Health. 2015;51(7):689–695.

 

 

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