Hypermobile Ehlers-Danlos Syndrome

Howard P Levy, Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Lora JH Bean, Karen W Gripp, Anne Amemiya, Howard P Levy, Margaret P Adam, Jerry Feldman, Ghayda M Mirzaa, Roberta A Pagon, Stephanie E Wallace, Lora JH Bean, Karen W Gripp, Anne Amemiya

Excerpt

Clinical characteristics: Hypermobile Ehlers-Danlos syndrome (hEDS) is generally considered the least severe type of EDS, although significant complications, primarily musculoskeletal, can and do occur. The skin is often soft and may be mildly hyperextensible. Subluxations and dislocations are common; they may occur spontaneously or with minimal trauma and can be acutely painful. Degenerative joint disease is common. Chronic pain, distinct from that associated with acute dislocations, is a serious complication of the condition and can be both physically and psychologically disabling. Easy bruising, functional bowel disorders, and cardiovascular autonomic dysfunction are common. Aortic root dilatation, when present, is typically of a mild degree with no increased risk of dissection in the absence of significant dilatation. Psychological dysfunction, psychosocial impairment, and emotional problems are common.

Diagnosis/testing: The diagnosis of hEDS is based entirely on clinical evaluation and family history. The gene(s) in which mutation causes hEDS are unknown and unmapped.

Management: Treatment of manifestations: Physical therapy tailored to the individual; assistive devices (braces to improve joint stability; wheelchair or scooter to offload stress on lower-extremity joints; suitable mattress to improve sleep quality); pain medication tailored to symptoms; appropriate therapy for gastritis/reflux/delayed gastric emptying/irritable bowel syndrome; psychological and/or pain-oriented counseling.

Prevention of primary manifestations: Low-resistance exercise to increase both core and extremity muscle tone for improved joint stability; appropriate writing utensils to reduce finger and hand strain.

Prevention of secondary complications: Calcium, vitamin D, low-impact weight-bearing exercise to maximize bone density.

Surveillance: DXA every other year if bone loss is confirmed.

Pregnancy management: Labor and delivery may progress very rapidly, even in primigravid women. There is no clear advantage to vaginal vs cesarean delivery. Pregnant women with known aortic root dilatation should have an echocardiogram in each trimester.

Agents/circumstances to avoid: High-impact activity increases the risk of acute subluxation/dislocation, chronic pain, and osteoarthritis.

Genetic counseling: Hypermobile EDS is inherited in an autosomal dominant manner. Most individuals diagnosed with the syndrome have an affected parent. The proportion of cases caused by a de novo pathogenic variant is unknown. Each child of an individual with hEDS has a 50% chance of inheriting the disorder. Because the gene(s) and pathogenic variant(s) responsible for hEDS have not been identified, prenatal testing is not possible.

Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

References

    1. Aldridge JM, 3rd, Perry JJ, Osbahr DC, Speer KP. Thermal capsulorraphy of bilateral glenohumeral joints in a pediatric patient with Ehlers-Danlos syndrome. Arthroscopy. 2003;19:E41.
    1. Anstey A, Mayne K, Winter M, Van de Pette J, Pope FM. Platelet and coagulation studies in Ehlers-Danlos syndrome. Br J Dermatol. 1991;125:155–63.
    1. Atzinger CL, Meyer RA, Khoury PR, Gao Z, Tinkle BT. Cross-sectional and longitudinal assessment of aortic root dilation and valvular anomalies in hypermobile and classic Ehlers-Danlos syndrome. J Pediatr. 2011;158:826–30.e1.
    1. Baeza-Velasco C, Gély-Nargeot MC, Bulbena Vilarrasa A, Bravo JF. Joint hypermobility syndrome: problems that require psychological intervention. Rheumatol Int. 2011;31:1131–6.
    1. Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Ehlers-Danlos National Foundation (USA) and Ehlers-Danlos Support Group (UK). Am J Med Genet. 1998;77:31–7.
    1. Beighton P, Solomon L, Soskolne CL. Articular mobility in an African population. Ann Rheum Dis. 1973;32:413–8.
    1. Branson JA, Kozlowska K, Kaczynski KJ, Roesler TA. Managing chronic pain in a young adolescent girl with Ehlers-Danlos syndrome. Harv Rev Psychiatry. 2011;19:259–70.
    1. Bristow J, Carey W, Egging D, Schalkwijk J. Tenascin-X, collagen, elastin, and the Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. 2005;139C:24–30.
    1. Camerota F, Castori M, Celletti C, Colotto M, Amato S, Colella A, Curione M, Danese C. Heart rate, conduction and ultrasound abnormalities in adults with joint hypermobility syndrome/Ehlers-Danlos syndrome, hypermobility type. Clin Rheumatol. 2014;33:981–7.
    1. Camerota F, Celletti C, Castori M, Grammatico P, Padua L. Neuropathic pain is a common feature in Ehlers-Danlos syndrome. J Pain Symptom Manage. 2011;41:e2–4.
    1. Campens L, Demulier L, De Groote K, Vandekerckhove K, De Wolf D, Roman MJ, Devereux RB, De Paepe A, De Backer J. Reference values for echocardiographic assessment of the diameter of the aortic root and ascending aorta spanning all age categories. Am J Cardiol. 2014;114:914–20.
    1. Carbone L, Tylavsky FA, Bush AJ, Koo W, Orwoll E, Cheng S. Bone density in Ehlers-Danlos syndrome. Osteoporos Int. 2000;11:388–92.
    1. Castori M, Camerota F, Celletti C, Danese C, Santilli V, Saraceni VM, Grammatico P. Natural history and manifestations of the hypermobility type Ehlers-Danlos syndrome: a pilot study on 21 patients. Am J Med Genet A. 2010a;152A:556–64.
    1. Castori M, Camerota F, Celletti C, Grammatico P, Padua L. Ehlers-Danlos syndrome hypermobility type and the excess of affected females: possible mechanisms and perspectives. Am J Med Genet A. 2010b;152A:2406–8.
    1. Castori M, Morlino S, Dordoni C, Celletti C, Camerota F, Ritelli M, Morrone A, Venturini M, Grammatico P, Colombi M. Gynecologic and obstetric implications of the joint hypermobility syndrome (a.k.a. Ehlers – Danlos syndrome hypermobility type) in 82 Italian patients. Am J Med Genet Part A. 2012;158A:2176–82.
    1. Castori M, Tinkle B, Levy H, Grahame R, Malfait F, Hakim A. A framework for the classification of joint hypermobility and related conditions. Am J Med Genet Part C Semin Med Genet. 2017;175:148–57.
    1. Chaudhury S, Gasinu S, Rodeo SA. Bilateral anterior and posterior glenohumeral stabilization using Achilles tendon allograft augmentation in a patient with Ehlers-Danlos syndrome. J Shoulder Elbow Surg. 2012;21:e1–5.
    1. Cimolin V, Galli M, Vismara L, Grugni G, Camerota F, Celletti C, Albertini G, Rigoldi C, Capodaglio P. Gait pattern in two rare genetic conditions characterized by muscular hypotonia: Ehlers-Danlos and Prader-Willi syndrome. Res Dev Disabil. 2011;32:1722–8.
    1. De Coster PJ, Martens LC, De Paepe A. Oral health in prevalent types of Ehlers-Danlos syndromes. J Oral Pathol Med. 2005;34:298–307.
    1. De Felice C, Bianciardi G, Dileo L, Latini G, Parrini S. Abnormal oral vascular network geometric complexity in Ehlers-Danlos syndrome. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2004;98:429–34.
    1. De Paepe A, Malfait F. Bleeding and bruising in patients with Ehlers-Danlos syndrome and other collagen vascular disorders. Br J Haematol. 2004;127:491–500.
    1. Dolan AL, Arden NK, Grahame R, Spector TD. Assessment of bone in Ehlers Danlos syndrome by ultrasound and densitometry. Ann Rheum Dis. 1998;57:630–3.
    1. Dolan AL, Mishra MB, Chambers JB, Grahame R. Clinical and echocardiographic survey of the Ehlers-Danlos syndrome. Br J Rheumatol. 1997;36:459–62.
    1. Dutta I, Wilson H, Oteri O. Pregnancy and delivery in ehlers-danlos syndrome (hypermobility type): review of the literature. Obstet Gynecol Int. 2011;2011:306413.
    1. Galli M, Cimolin V, Rigoldi C, Castori M, Celletti C, Albertini G, Camerota F. Gait strategy in patients with Ehlers-Danlos syndrome hypermobility type: a kinematic and kinetic evaluation using 3D gait analysis. Res Dev Disabil. 2011;32:1663–8.
    1. Gazit Y, Nahir AM, Grahame R, Jacob G. Dysautonomia in the joint hypermobility syndrome. Am J Med. 2003;115:33–40.
    1. Gharbiya M, Moramarco A, Castori M, Parisi F, Celletti C, Marenco M, Mariani I, Grammatico P, Camerota F. Ocular features in joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type: a clinical and in vivo confocal microscopy study. Am J Ophthalmol. 2012;154:593–600.e1.
    1. Grahame R. Joint hypermobility and genetic collagen disorders: are they related? Arch Dis Child. 1999;80:188–91.
    1. Gulbahar S, Sahin E, Baydar M, Bircan C, Kizil R, Manisali M, Akalin E, Peker O. Hypermobility syndrome increases the risk for low bone mass. Clin Rheumatol. 2006;25:511–4.
    1. Hagberg C, Berglund B, Korpe L, Andersson-Norinder J. Ehlers-Danlos Syndrome (EDS) focusing on oral symptoms: a questionnaire study. Orthod Craniofac Res. 2004;7:178–85.
    1. 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;57:163–166.
    1. Hakim AJ, Grahame R, Norris P, Hopper C. Local anaesthetic failure in joint hypermobility syndrome. J R Soc Med. 2005;98:84–5.
    1. Huang SJ, Amendola LM, Sternen DL. Variation among DNA banking consent forms: points for clinicians to bank on. J Community Genet. 2022;13:389–97.
    1. Jacome DE. Headache in Ehlers-Danlos syndrome. Cephalalgia. 1999;19:791–6.
    1. Juul-Kristensen B, Schmedling K, Rombaut L, Lund H, Engelbert RHH. Measurement properties of clinical assessment methods for classifying generalized joint hypermobility—A systematic review. Am J Med Genet Part C Semin Med Genet. 2017;175:116–47.
    1. Kozanoglu E, Coskun Benlidayi I, Eker Akilli R, Tasal A. Is there any link between joint hypermobility and mitral valve prolapse in patients with fibromyalgia syndrome? Clin Rheumatol. 2016;35:1041–4.
    1. Levy HP, Mayoral W, Collier K, Tio TL, Fracomano CA. Gastroesophageal reflux and irritable bowel syndrome in classical and hypermobile Ehlers Danlos syndrome (EDS). Am J Hum Genet. 1999;65:A69.
    1. 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. The 2017 international classification of the Ehlers-Danlos syndromes. Am J Med Genet C Semin Med Genet. 2017;175:8–26.
    1. Mast KJ, Nunes ME, Ruymann FB, Kerlin BA. Desmopressin responsiveness in children with Ehlers-Danlos syndrome associated bleeding symptoms. Br J Haematol. 2009;144:230–3.
    1. Mathias CJ, Low DA, Iodice V, Owens AP, Kirbis M, Grahame R. Postural tachycardia syndrome--current experience and concepts. Nat Rev Neurol. 2011;8:22–34.
    1. McDonnell NB, Gorman BL, Mandel KW, Schurman SH, Assanah-Carroll A, Mayer SA, Najjar SS, Francomano CA. Echocardiographic findings in classical and hypermobile Ehlers-Danlos syndromes. Am J Med Genet A. 2006;140:129–36.
    1. McIntosh LJ, Mallett VT, Frahm JD, Richardson DA, Evans MI. Gynecologic disorders in women with Ehlers-Danlos syndrome. J Soc Gynecol Investig. 1995;2:559–64.
    1. Milhorat TH, Bolognese PA, Nishikawa M, McDonnell NB, Francomano CA. Syndrome of occipitoatlantoaxial hypermobility, cranial settling, and chiari malformation type I in patients with hereditary disorders of connective tissue. J Neurosurg Spine. 2007;7:601–9.
    1. Pacey V, Tofts L, Adams RD, Munns CF, Nicholson LL. Exercise in children with joint hypermobility syndrome and knee pain: a randomised controlled trial comparing exercise into hypermobile versus neutral knee extension. Pediatr Rheumatol Online J. 2013;11:30–40.
    1. Rigoldi C, Galli M, Cimolin V, Camerota F, Celletti C, Tenore N, Albertini G. Gait strategy in patients with Ehlers-Danlos syndrome hypermobility type and Down syndrome. Res Dev Disabil. 2012;33:1437–42.
    1. Rombaut L, De Paepe A, Malfait F, Cools A, Calders P. Joint position sense and vibratory perception sense in patients with Ehlers-Danlos syndrome type III (hypermobility type). Clin Rheumatol. 2010a;29:289–95.
    1. Rombaut L, Malfait F, Cools A, De Paepe A, Calders P. Musculoskeletal complaints, physical activity and health-related quality of life among patients with the Ehlers-Danlos syndrome hypermobility type. Disabil Rehabil. 2010b;32:1339–45.
    1. Rombaut L, Malfait F, De Paepe A, Rimbaut S, Verbruggen G, De Wandele I, Calders P. Impairment and impact of pain in female patients with Ehlers-Danlos syndrome: a comparative study with fibromyalgia and rheumatoid arthritis. Arthritis Rheum. 2011a;63:1979–87.
    1. Rombaut L, Malfait F, De Wandele I, Cools A, Thijs Y, De Paepe A, Calders P. Medication, surgery, and physiotherapy among patients with the hypermobility type of Ehlers-Danlos syndrome. Arch Phys Med Rehabil. 2011b;92:1106–12.
    1. Rombaut L, Malfait F, De Wandele I, Mahieu N, Thijs Y, Segers P, De Paepe A, Calders P. Muscle-tendon tissue properties in the hypermobility type of Ehlers-Danlos syndrome. Arthritis Care Res (Hoboken) 2012a;64:766–72.
    1. Rombaut L, Malfait F, De Wandele I, Taes Y, Thijs Y, De Paepe A, Calders P. Muscle mass, muscle strength, functional performance,and physical impairment in women with the hypermobility type of Ehlers-Danlos syndrome. Arthritis Care Res (Hoboken) 2012b;64:1584–92.
    1. Rombaut L, Malfait F, De Wandele I, Thijs Y, Palmans T, De Paepe A, Calders P. Balance, gait, falls, and fear of falling in women with the hypermobility type of Ehlers-Danlos syndrome. Arthritis Care Res (Hoboken) 2011c;63:1432–9.
    1. Rose PS, Johnson CA, Hungerford DS, McFarland EG. Total knee arthroplasty in Ehlers-Danlos syndrome. J Arthroplasty. 2004;19:190–6.
    1. Rowe PC, Barron DF, Calkins H, Maumenee IH, Tong PY, Geraghty MT. Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome. J Pediatr. 1999;135:494–9.
    1. Sacheti A, Szemere J, Bernstein B, Tafas T, Schechter N, Tsipouras P. Chronic pain is a manifestation of the Ehlers-Danlos syndrome. J Pain Symptom Manage. 1997;14:88–93.
    1. Stine KC, Becton DL. DDAVP therapy controls bleeding in Ehlers-Danlos syndrome. J Pediatr Hematol Oncol. 1997;19:156–8.
    1. Symoens S, Syx D, Malfait F, Callewaert B, De Backer J, Vanakker O, Coucke P, De Paepe A. Comprehensive molecular analysis demonstrates type V collagen mutations in over 90% of patients with classic EDS and allows to refine diagnostic criteria. Hum Mutat. 2012;33:1485–93.
    1. Tinkle BT, Bird HA, Grahame R, Lavallee M, Levy HP, Sillence D. 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:2368–70.
    1. Voermans NC, Knoop H. Both pain and fatigue are important possible determinants of disability in patients with the Ehlers-Danlos syndrome hypermobility type. Disabil Rehabil. 2011;33:706–7.
    1. Voermans NC, Knoop H, Bleijenberg G, van Engelen BG. Pain in ehlers-danlos syndrome is common, severe, and associated with functional impairment. J Pain Symptom Manage. 2010a;40:370–8.
    1. Voermans NC, Knoop H, van de Kamp N, Hamel BC, Bleijenberg G, van Engelen BG. Fatigue is a frequent and clinically relevant problem in Ehlers-Danlos syndrome. Semin Arthritis Rheum. 2010b;40:267–74.
    1. Volkov N, Nisenblat V, Ohel G, Gonen R. Ehlers-Danlos syndrome: insights on obstetric aspects. Obstet Gynecol Surv. 2007;62:51–7.
    1. Wenstrup RJ, Meyer RA, Lyle JS, Hoechstetter L, Rose PS, Levy HP, Francomano CA. Prevalence of aortic root dilation in the Ehlers-Danlos syndrome. Genet Med. 2002;4:112–7.
    1. Zweers MC, Bristow J, Steijlen PM, Dean WB, Hamel BC, Otero M, Kucharekova M, Boezeman JB, Schalkwijk J. Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome. Am J Hum Genet. 2003;73:214–7.
    1. Zweers MC, Dean WB, van Kuppevelt TH, Bristow J, Schalkwijk J. Elastic fiber abnormalities in hypermobility type Ehlers-Danlos syndrome patients with tenascin-X mutations. Clin Genet. 2005;67:330–4.

Source: PubMed

Patrocinadores y Colaboradores

Condiciones médicas

Intervenciones de drogas

3
Suscribir