Joint hypermobility syndrome
- Rodney Grahame, MD, FRCP, FACP
Rodney Grahame, MD, FRCP, FACP
- Honorary Professor
- University College London
- Affiliate Professor
- University of Washington
- Alan J Hakim, BA MB BChir
Alan J Hakim, BA MB BChir
- Honorary Senior Lecturer
- St Bartholomews and The London School of Medicine and Dentistry
- Queen Mary, University of London
The joint hypermobility syndrome (JHS) is the most common disorder among the hereditary disorders of connective tissue (HDCT), a group of conditions that include JHS, Ehlers-Danlos syndrome (EDS), Marfan syndrome, osteogenesis imperfecta, and Stickler syndrome. Joint hypermobility (JHM) may be of no medical consequence and might even confer advantages for dancers, musicians, and athletes; however, it may also be associated with a number of comorbidities that constitute the cardinal features of the HDCT.
JHS is considered by many experts to be indistinguishable from, if not identical to, the most common variant of Ehlers-Danlos syndrome (EDS), EDS-hypermobility type (EDS-HM). (See 'Epidemiology' below.)
JHS is reviewed here. Overviews of the clinical manifestations, diagnosis, and management of the Ehlers-Danlos syndromes; the clinical manifestations and treatment of the Marfan syndrome; osteogenesis imperfecta; and the Stickler syndrome are presented separately. (See "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes" and "Overview of the management of Ehlers-Danlos syndromes" and "Genetics, clinical features, and diagnosis of Marfan syndrome and related disorders" and "Osteogenesis imperfecta: Clinical features and diagnosis" and "Osteogenesis imperfecta: Management and prognosis" and "Syndromes with craniofacial abnormalities", section on 'Stickler and Marshall syndromes'.)
Joint hypermobility syndrome (JHS) is very common in musculoskeletal disease clinics, but the diagnosis is often missed, and the actual prevalence of JHS is not known [1,2]. In one large survey in the United Kingdom, the combination of joint hypermobility (JHM) and chronic widespread pain, which is typical of many patients with JHS, was found in 3 percent of a general population . There has been a lack of general population studies or other studies of sufficient sample size to accurately estimate the prevalence of JHS .
JHS is considered by many experts in rheumatology and in clinical genetics to be indistinguishable from, if not identical to, the most common variant of Ehlers-Danlos syndrome (EDS), EDS-hypermobility type (EDS-HM), but the precise relationship between EDS-HM and JHS remains uncertain [5,6]. (See "Clinical manifestations and diagnosis of Ehlers-Danlos syndromes".)
- Grahame R. Hypermobility: an important but often neglected area within rheumatology. Nat Clin Pract Rheumatol 2008; 4:522.
- Hakim AJ, Grahame R. High prevalence of joint hypermobility syndrome in clinic referrals to a North London community hospital. Rheumatology 2004; 43 suppl 1:198.
- 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; 65:1325.
- Fikree A, Aziz Q, Grahame R. Joint hypermobility syndrome. Rheum Dis Clin North Am 2013; 39:419.
- Tinkle BT, Bird HA, Grahame R, et al. 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 2009; 149A:2368.
- Castori M, Dordoni C, Valiante M, et al. Nosology and inheritance pattern(s) of joint hypermobility syndrome and Ehlers-Danlos syndrome, hypermobility type: a study of intrafamilial and interfamilial variability in 23 Italian pedigrees. Am J Med Genet A 2014; 164A:3010.
- Hakim AJ, Cherkas LF, Grahame R, et al. The genetic epidemiology of joint hypermobility: a population study of female twins. Arthritis Rheum 2004; 50:2640.
- Bravo JF, Wolff C. Clinical study of hereditary disorders of connective tissues in a Chilean population: joint hypermobility syndrome and vascular Ehlers-Danlos syndrome. Arthritis Rheum 2006; 54:515.
- Rombaut L, Malfait F, Cools A, et al. Musculoskeletal complaints, physical activity and health-related quality of life among patients with the Ehlers-Danlos syndrome hypermobility type. Disabil Rehabil 2010; 32:1339.
- Voermans NC, Knoop H, van de Kamp N, et al. Fatigue is a frequent and clinically relevant problem in Ehlers-Danlos Syndrome. Semin Arthritis Rheum 2010; 40:267.
- Ross J, Grahame R. Joint hypermobility syndrome. BMJ 2011; 342:c7167.
- Hakim AJ, Sahota A. Joint hypermobility and skin elasticity: the hereditary disorders of connective tissue. Clin Dermatol 2006; 24:521.
- Zweers MC, Hakim AJ, Grahame R, Schalkwijk J. Joint hypermobility syndromes: the pathophysiologic role of tenascin-X gene defects. Arthritis Rheum 2004; 50:2742.
- Malfait F, Hakim AJ, De Paepe A, Grahame R. The genetic basis of the joint hypermobility syndromes. Rheumatology (Oxford) 2006; 45:502.
- 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; 33:2709.
- Shaikh M, Hakim AJ, Shenker N. The physiology of pain. In: Hypermobility, Fibromyalgia, and Chronic Pain, Hakim A, Keer R, Grahame R. (Eds), Elsevier, Churchill Livingstone, London 2010. p.25.
- Castori M, Morlino S, Celletti C, et al. Management of pain and fatigue in the joint hypermobility syndrome (a.k.a. Ehlers-Danlos syndrome, hypermobility type): principles and proposal for a multidisciplinary approach. Am J Med Genet A 2012; 158A:2055.
- Hakim AJ, Grahame R. Non-musculoskeletal symptoms in joint hypermobility syndrome. Indirect evidence for autonomic dysfunction? Rheumatology (Oxford) 2004; 43:1194.
- Mathias CJ, Low DA, Iodice V, et al. Postural tachycardia syndrome--current experience and concepts. Nat Rev Neurol 2011; 8:22.
- Nelson AD, Mouchli MA, Valentin N, et al. Ehlers Danlos syndrome and gastrointestinal manifestations: a 20-year experience at Mayo Clinic. Neurogastroenterol Motil 2015; 27:1657.
- Zarate N, Farmer AD, Grahame R, et al. Unexplained gastrointestinal symptoms and joint hypermobility: is connective tissue the missing link? Neurogastroenterol Motil 2010; 22:252.
- Fikree A, Grahame R, Aktar R, et al. A prospective evaluation of undiagnosed joint hypermobility syndrome in patients with gastrointestinal symptoms. Clin Gastroenterol Hepatol 2014; 12:1680.
- 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; 24:1553.
- Bulbena A, Gago J, Pailhez G, et al. Joint hypermobility syndrome is a risk factor trait for anxiety disorders: a 15-year follow-up cohort study. Gen Hosp Psychiatry 2011; 33:363.
- Smith TO, Easton V, Bacon H, et al. The relationship between benign joint hypermobility syndrome and psychological distress: a systematic review and meta-analysis. Rheumatology (Oxford) 2014; 53:114.
- Grahame R, Hakim AJ. Arachnodactyly--a key to diagnosing heritable disorders of connective tissue. Nat Rev Rheumatol 2013; 9:358.
- Grahame R, Bird HA, Child A. The revised (Brighton 1998) criteria for the diagnosis of benign joint hypermobility syndrome (BJHS). J Rheumatol 2000; 27:1777.
- 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; 57:163.
- Loeys BL, Dietz HC, Braverman AC, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet 2010; 47:476.
- Beighton P, De Paepe A, Steinmann B, et al. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet 1998; 77:31.
- HMSA - The Hypermobility Syndromes Association. http://www.hypermobility.org (Accessed on February 25, 2014).
- EDNF - The Ehlers-Danlos National Foundation. http://www.ednf.org/ (Accessed on March 08, 2014).
- Ferrell WR, Tennant N, Sturrock RD, et al. Amelioration of symptoms by enhancement of proprioception in patients with joint hypermobility syndrome. Arthritis Rheum 2004; 50:3323.
- Simmonds JV, Keer RJ. Hypermobility and the hypermobility syndrome. Man Ther 2007; 12:298.
- Simmonds JV, Keer RJ. Hypermobility and the hypermobility syndrome, part 2: assessment and management of hypermobility syndrome: illustrated via case studies. Man Ther 2008; 13:e1.
- Celletti C, Castori M, La Torre G, Camerota F. Evaluation of kinesiophobia and its correlations with pain and fatigue in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type. Biomed Res Int 2013; 2013:580460.
- Hakim AJ, Ashton S. Undiagnosed joint hypermobility syndrome patients have poorer outcome than peers following chronic back pain rehabilitation. Rheumatology 2005; 44 (suppl 1):i106.
- 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; 36:797.
- Hakim A. A Patient Survey of Treatment Outcomes in Joint Hypermobility Syndrome. HMSA Newsletter, 2012. p.25.
- Holman AJ. Positional cervical spinal cord compression and fibromyalgia: a novel comorbidity with important diagnostic and treatment implications. J Pain 2008; 9:613.
- Milhorat TH, Bolognese PA, Nishikawa M, et al. Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and chiari malformation type I in patients with hereditary disorders of connective tissue. J Neurosurg Spine 2007; 7:601.
- NATURAL HISTORY
- CLINICAL MANIFESTATIONS
- Beighton score for joint hypermobility
- Brighton criteria for JHS diagnosis
- DIFFERENTIAL DIAGNOSIS
- Marfan syndrome
- Ehlers-Danlos syndrome
- SUPPLEMENTAL AND POSTDIAGNOSTIC EVALUATION
- Patient education and self-management
- Musculoskeletal manifestations and pain
- Referral for associated manifestations
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS