Heritable Hypermobility Syndromes

  • Peter Beighton
  • Rodney Grahame
  • Howard Bird


The heritable hypermobility syndromes are a group of disorders in which joint laxity is a prominent feature. In some of these conditions, the loose joints predispose to a wide variety of articular complications and, despite their rarity, they are of considerable rheumatological importance.


Osteogenesis Imperfecta Club Foot Marfan Syndrome Mitral Valve Prolapse Joint Laxity 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Ehlers E. Cutis Laxa, Neigung zu Haemorrhagien in der Haut, Lockerung Mehrer Artikulationen. Derm Zschr [Denmark]. 1901;8:173-175.Google Scholar
  2. 2.
    Danlos M. Un cas de cutis laxa avec tumeurs par contusion chronique des coudes et des genous (xanthome juvenile pseudodiabetique de MM Hallopeau et Mace de Lepinay). Bull Soc Franc Derm Syph. 1908;19:70-72.Google Scholar
  3. 3.
    Beighton P. The Ehlers-Danlos Syndrome. London: William Heinemann Medical Books; 1970.Google Scholar
  4. 4.
    Beighton P, ed. McKusick’s Heritable Disorders of Connective Tissue). 5th ed. St. Louis: Mosby; 1993.Google Scholar
  5. 5.
    Royce PM, Steinmann B, eds. Connective Tissue and Its Heritable Disorders: Molecular, Genetic, and Medical Aspects. New York/Chichester/Brisbane/Toronto/Singapore: Wiley; 1993.Google Scholar
  6. 6.
    Wenstrup R, De Paepe A. Ehlers-Danlos syndrome, classic type: reviews at Gene-Tests-GeneClinics [database online]. Available at, 2010.
  7. 7.
    Levy HP. Ehlers-Danlos syndrome, hypermobility type: reviews at Gene-Tests-GeneClinics [database online]. Available at, 2007.
  8. 8.
    Pepin MG, Byers PH. Ehlers-Danlos syndrome, vascular type: reviews at Gene-Tests-GeneClinics [database online]. Available at, 2006.
  9. 9.
    Yeowel HN, Steinmann B. Ehlers-Danlos syndrome, kyphoscoliotic form; reviews at Gene-Tests-GeneClinics [database online]. Available at, 2008.
  10. 10.
    Yeowell HN, Steinmann B. Ehlers-Danlos syndrome, kyphoscoliotic form: gene reviews [Internet]. Seattle: University of Washington, Seattle. Initial Posting: 2 February 2000; Last Update: 19 February 2008.Google Scholar
  11. 11.
    Barabas AP. Heterogeneity of the Ehlers-Danlos syndrome: description of three clinical types and a hypothesis to explain the basic defect(s). Br Med J. 1967;2:612-616.PubMedGoogle Scholar
  12. 11a.
    Beighton P. Inherited disorders of the skeleton. 2nd ed. Edinburgh/London/New York: Churchill Livingstone; 1988.Google Scholar
  13. 12.
    Beighton P, Murdoch JL, Votteler T. Gastrointestinal complication of the Ehlers-Danlos syndrome. Gut. 1969;10:1004-1008.PubMedGoogle Scholar
  14. 13.
    Beighton P, De Paepe A, Steinmann B, Tsipouras P, Wenstrup RJ. Ehlers-Danlos syndromes: revised nosology, Villefranche, 1997. Am J Med Genet. 1998;77:31-37.PubMedGoogle Scholar
  15. 14.
    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.PubMedGoogle Scholar
  16. 15.
    Giunta C, Nuytinck L, Raghunath M, Hausser I, De Paepe A, Steinmann B. Homozygous Gly530Ser substitution in COL5A1 causes mild classical Ehlers-Danlos syndrome. Am J Med Genet. 2002;109:284-290.PubMedGoogle Scholar
  17. 16.
    Malfait F, Coucke P, Symoens S, Loeys B, Nuytinck L, De Paepe A. The molecular basis of classic Ehlers-Danlos syndrome: a comprehensive study of biochemical and molecular findings in 48 unrelated patients. Hum Mutat. 2005;25:28-37.PubMedGoogle Scholar
  18. 17.
    Malfait F, De Paepe A. Molecular genetics in classic Ehlers-Danlos syndrome. Am J Med Genet C Semin Med Genet. 2005;139C:17-23.PubMedGoogle Scholar
  19. 17a.
    Grahame R. Joint hypermobility and genetic collagen disorders: are they related? Arch Dis Child. 1999;80:188-191.PubMedGoogle Scholar
  20. 18.
    Malfait F, Hakim AJ, De Paepe A, Grahame R. The genetic basis of joint hypermobility syndromes. Rheumatology. 2006;45:502-507.PubMedGoogle Scholar
  21. 19.
    Schalkwijk J, Zweers MC, Steijlen PM, et al. A recessive form of the Ehlers-Danlos syndrome caused by tenascin-X deficiency. N Engl J Med. 2001;345:1167-1175.PubMedGoogle Scholar
  22. 20.
    Zweers MC, Bristow J, Steijlen PM, et al. Haploinsufficiency of TNXB is associated with hypermobility type of Ehlers-Danlos syndrome. Am J Hum Genet. 2003;73:214-217.PubMedGoogle Scholar
  23. 21.
    Zweers MC, Hakim AJ, Grahame R, Schalkwijk J. Joint hypermobility syndromes: the pathphysiologic role of tenascin-X gene defects. Arthritis Rheum. 2004;50(9):2742-2749.PubMedGoogle Scholar
  24. 22.
    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;67:330-334.PubMedGoogle Scholar
  25. 23.
    Fuchs JR, Fishman SJ. Management of spontaneous colonic perforation in Ehlers and Danlos syndrome type IV. J Pediatr Surg. 2004;39:e1-e3.PubMedGoogle Scholar
  26. 24.
    Chuman H, Trobe JD, Petty EM, et al. Spontaneous direct carotid-cavernous fistula in Ehlers-Danlos syndrome type IV: two case reports and a review of the literature. J Neuroophthalmol. 2002;22(2):73-74.Google Scholar
  27. 25.
    Hollands JK, Santarius T, Kirkpatrick PJ, Higgins JN. Treatment of a direct carotid-cavernous fistula in a patient with type IV Ehlers-Danlos syndrome: a novel approach. Neuroradiology. 2006;48(7):491-494, Epub 2006 May 6.PubMedGoogle Scholar
  28. 26.
    Naidu SG, Chong BW, Huettl EA, Stone WM. Percutaneous embolization of a lumbar pseudoaneurysm in a patient with type IV Ehlers-Danlos syndrome. J Vasc Surg. 2008;47(6):1376.Google Scholar
  29. 27.
    Freeman RK, Swegle J, Sise MJ. The surgical complications of Ehlers-Danlos syndrome. Am Surg. 1996;62:869-873.PubMedGoogle Scholar
  30. 28.
    Oderich GS, Panneton JM, Bower TC, et al. The spectrum, management and clinical outcome of Ehlers-Danlos syndrome type IV: a 30-year experience. J Vasc Surg. 2005;42:98-106.PubMedGoogle Scholar
  31. 29.
    Pepin M, Schwarze U, Superti-Furga A, Byers PH. Clinical and genetic features of Ehlers-Danlos syndrome type IV, the vascular type. N Engl J Med. 2000;342:673-680.PubMedGoogle Scholar
  32. 30.
    Okamoto O, Ando T, Watanabe A, Mimata H, Shimada T, Fujiwara SA. A novel point mutation in type III collagen gene resulting in exon 24 skipping in a case of vascular type Ehlers-Danlos syndrome. Arch Dermatol Res. 2008;300:525-529.PubMedGoogle Scholar
  33. 31.
    Combeer EL, Combeer AD. A rare cause of maternal death: liver and inferior vena cava rupture due to previously undiagnosed Ehlers-Danlos Syndrome type IV. Eur J Anaesthesiol. 2008;25:765-767.PubMedGoogle Scholar
  34. 32.
    Al-Hussain H, Zeisberger SM, Huber PR, Giunta C, Steinmann B. Brittle cornea syndrome and its delineation from the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI): report on 23 patients and review of the literature. Am J Med Genet A. 2004;124:28-34.Google Scholar
  35. 33.
    Yeowell HN, Walker LC. Mutations in the lysyl hydroxylase 1 gene that result in enzyme deficiency and the clinical phenotype of Ehlers-Danlos syndrome type VI. Mol Genet Metab. 2000;71:212-224.PubMedGoogle Scholar
  36. 34.
    Giunta C, Randolph A, Steinmann B. Mutation analysis of the PLOD1 gene: an efficient multistep approach to the molecular diagnosis of the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VIA). Mol Genet Metab. 2005;86:269-276.PubMedGoogle Scholar
  37. 35.
    Viljoen D, Goldblatt J, Thompson D, Beighton P. Ehlers-Danlos syndrome: yet another type. Clin Genet. 1987;32:196-201.PubMedGoogle Scholar
  38. 36.
    Giunta C, Chambaz C, Pedemonte M, Scapolan S, Steinmann B. The arthrochalasia type of Ehlers-Danlos syndrome (EDS VIIA and VIIB): the diagnostic value of collagen fibril ultrastructure. Am J Med Genet A. 2008;146A(10):1341-1346.PubMedGoogle Scholar
  39. 37.
    Schwarze U, Hata R, et al. Rare autosomal recessive cardiac valvular form of Ehlers-Danlos syndrome results from mutations in the COL1A2 gene that activate the nonsense-mediated RNA decay pathway. Am J Hum Genet. 2004;74(5):917-930.PubMedGoogle Scholar
  40. 38.
    Malfait F, Symoens S, Coucke P, Nunes L, De Almeida S, De Paepe A. Total absence of the alpha2(I) chain of collagen type I causes a rare form of Ehlers-Danlos syndrome with hypermobility and propensity to cardiac valvular problems. J Med Genet. 2006;43(7):e36.PubMedGoogle Scholar
  41. 39.
    Malfait F, Symoens S, De Backer J, et al. Three arginine to cysteine substitutions in the pro-alpha (I)-collagen chain cause Ehlers-Danlos syndrome with a propensity to arterial rupture in early adulthood. Hum Mutat. 2007;28:387-395.PubMedGoogle Scholar
  42. 40.
    Giunta C, Elçioglu NH, Albrecht B, et al. Spondylocheiro dysplastic form of the Ehlers-Danlos syndrome–an autosomal-recessive entity caused by mutations in the zinc transporter gene SLC39A13. Am J Hum Genet. 2008;82(6):1290-1305.PubMedGoogle Scholar
  43. 41.
    Raff ML, Craigen WJ, Smith LT, et al. Partial COL1A2 gene duplication produces features of osteogenesis imperfecta and Ehlers-Danlos syndrome type VII. Hum Genet. 2000;106:19-28.PubMedGoogle Scholar
  44. 42.
    Cabral WA, Chung W, Barnes AM, et al. Prolyl 3-hydroxylase 1 deficiency causes a recessive metabolic bone disorder resembling lethal/severe osteogenesis imperfecta. Nat Genet. 2007;39:359-365.PubMedGoogle Scholar
  45. 43.
    Beighton P, Horan F. Orthopaedic aspects of the Ehlers-Danlos syndrome. J Bone Joint Surg Br. 1969;51B:414-449.Google Scholar
  46. 44.
    Kay RM, Skaggs DL. Bilateral hip dislocations in a father and son with Ehlers-Danlos syndrome. Orthopedics. 2001;24:1165-1166.PubMedGoogle Scholar
  47. 45.
    Hagberg C, Korpe L, Berglund B. Temporomandibular joint problems and self-registration of mandibular opening capacity among adults with Ehlers-Danlos syndrome: a questionnaire study. Orthod Craniofac Res. 2004;7:40-46.PubMedGoogle Scholar
  48. 46.
    Dabbas N, Saker R, Blakeley C. Multiple spontaneous dislocations in a patient with Ehlers–Danlos syndrome. Emerg Med J. 2008;25:175-176.PubMedGoogle Scholar
  49. 47.
    Schroeder EL, Lavallee ME. Ehlers-Danlos syndrome in athletes. Curr Sports Med Rep. 2006;6:327-334.Google Scholar
  50. 48.
    Giordano P, Del Vecchio GC, Scaraggi R, et al. Hemarthrosis due to a rare cause of hemorrhagic diathesis: Ehlers-Danlos syndrome. Pediatr Hematol Oncol. 2008;25(3):205-209.PubMedGoogle Scholar
  51. 49.
    Yis U, Dirik E, Chambaz C, et al. Differential diagnosis of muscular hypotonia in infants: the kyphoscoliotic type of Ehlers-Danlos syndrome (EDS VI). Neuromuscul Disord. 2008;18(3):210-214.PubMedGoogle Scholar
  52. 50.
    Nematbakhsh A, Crawford A. Non-adjacent spondylolisthesis in Ehlers–Danlos syndrome. J Pediatr Orthop B. 2004;13(5):336-339.PubMedGoogle Scholar
  53. 51.
    Wenstrup RJ, Meyer RA, Lyle JS, et al. Prevalence of aortic root dilation in the Ehlers-Danlos syndrome. Genet Med. 2002;4:112-117.PubMedGoogle Scholar
  54. 52.
    Berglund B, Nordstrom G, Hagberg C, Mattiasson AC. Foot pain and disability in individuals with Ehlers-Danlos syndrome (EDS): impact on daily life activities. Disabil Rehabil. 2005;27(4):164-169.PubMedGoogle Scholar
  55. 53.
    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(2):88-93.PubMedGoogle Scholar
  56. 54.
    Hulme JR, Wilmshurst CC. Acute appendicitis in the Ehlers-Danlos syndrome. Am J Surg. 1976;132:103-104.PubMedGoogle Scholar
  57. 55.
    Umekoji A, Fukai K, Hosomi N, et al. Vascular type of Ehlers-Danlos syndrome associated with mild haemophilia A. Clin Exp Dermatol. 2009;34(1):101.PubMedGoogle Scholar
  58. 56.
    Akpina S, Gogus A, Talu U, Hamzaoglu A, Dikici F. Surgical management of the spinal deformity in Ehlers-Danlos syndrome type VI. Eur Spine J. 2003;12:135-140.Google Scholar
  59. 57.
    Rose PS, Johnson CA, Hungerford DS, McFarland EG. Total knee arthroplasty in Ehlers-Danlos syndrome. J Arthroplasty. 2004;19(2):190-196.PubMedGoogle Scholar
  60. 58.
    Qureshi SA, Shah AK, Pruzansky ME. Using the semitendinosus tendon to stabilize sternoclavicular joints in a patient with Ehlers-Danlos syndrome: a case report. Am J Orthop. 2005;34(7):315-318.PubMedGoogle Scholar
  61. 59.
    Badia A, Riano F, Young LC. Bilateral arthroscopic tendon interposition arthroplasty of the thumb carpometacarpal joint in a patient with Ehlers-Danlos syndrome: a case report. J Hand Surg [Am]. 2005;30(4):673-676.Google Scholar
  62. 60.
    Lane D. Anaesthetic implications of vascular type Ehlers-Danlos syndrome. Anaesth Intensive Care. 2006;34(4):501-505.PubMedGoogle Scholar
  63. 61.
    Hakim AJ, Grahame R, Norris P, Hopper C. Local anaesthetic failure in joint hypermobility syndrome. J R Soc Med. 2005;98:84-85.PubMedGoogle Scholar
  64. 62.
    Dolan AL, Mishra MB, Chambers JB, Grahame R. Clinical and echocardiographic survey of the Ehlers-Danlos syndrome. Br J Rheumatol. 1997;36(4):459-462.PubMedGoogle Scholar
  65. 63.
    McDonnell NB, Gorman BL, Mandel KW, et al. Echocardiographic findings in classical and hypermobile Ehlers-Danlos syndromes. Am J Med Genet A. 2006;140(2):129-136.PubMedGoogle Scholar
  66. 64.
    Volkov N, Nisenblat V, Ohel G, Gonen R. Ehlers-Danlos syndrome: insights on obstetric aspects. Obstet Gynecol Surv. 2007;62:51-57.PubMedGoogle Scholar
  67. 65.
    Carley ME, Schaffer J. Urinary incontinence and pelvic organ prolapse in women with Marfan or Ehlers Danlos syndrome. Am J Obstet Gynecol. 2000;182:1021-1023.PubMedGoogle Scholar
  68. 66.
    De Coster PJ, Martens LC, De Paepe A. Oral health in prevalent types of Ehlers-Danlos syndromes. J Oral Pathol Med. 2005;34(5):298-307.PubMedGoogle Scholar
  69. 67.
    Abel MD, Carrasco LR. Ehlers-Danlos syndrome: classifications, oral manifestations, and dental considerations. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2006;102(5):582-590.PubMedGoogle Scholar
  70. 68.
    De Coster PJ, Martens LC, Van den Berghe L. Prevalence of temporomandibular joint dysfunction in Ehlers–Danlos syndromes. Orthod Craniofac Res. 2004;7:237-240.PubMedGoogle Scholar
  71. 69.
    Ferreira O Jr, Cardoso CL, Capelozza AL, Yaedú RY, da Costa AR. Odontogenic keratocyst and multiple supernumerary teeth in a patient with Ehlers-Danlos syndrome–a case report and review of the literature. Quintessence Int. 2008;39(3):251-256.PubMedGoogle Scholar
  72. 70.
    Villan S, Sever A, Mills P, Mounter NA, Sever AR. Unusual breast calcification due to Ehlers-Danlos syndrome, detected by mammography. Clin Radiol. 2005;60(11):1216-1218.PubMedGoogle Scholar
  73. 71.
    Tapley E, Beighton P. Calcification of breast tissue in the Ehlers–Danlos syndrome. Breast J. 2009;15:537-539.PubMedGoogle Scholar
  74. 72.
    Key JA. Hypermobility of joints as a sex-linked hereditary characteristic. JAMA. 1927;88:1710-1712.Google Scholar
  75. 73.
    Sturkie PD. Hypermobile joints in all descendants for two generations. J Hered. 1941;32:232-234.Google Scholar
  76. 74.
    Haas J, Hass R. Arthrochalasis multiplex congenita; congenital flaccidity of the joints. J Bone Joint Surg Am. 1958;40A:663-674.Google Scholar
  77. 75.
    Carter C, Sweetnam R. Familial joint laxity and recurrent dislocations of the patella. J Bone Joint Surg Br. 1958;40B:664-667.Google Scholar
  78. 76.
    Carter C, Sweetman R. Recurrent dislocation of the patella and of the shoulder, their association with familial laxity. J Bone Joint Surg Br. 1960;42B:721-727.Google Scholar
  79. 77.
    Carter C, Wilkinson J. Persistent joint laxity and congenital dislocation of the hip. J Bone Joint Surg Br. 1964;46B:40-45.Google Scholar
  80. 78.
    Whitney LF. Inheritance of double-jointedness of the thumb. J Hered. 1932;23:425-426.Google Scholar
  81. 79.
    Shapiro SD, Jorgenson RJ, Salinas CF. Recurrent dislocation of the patella versus generalized joint laxity. The National Foundation. Birth Defects. 1976;XII:287-291.Google Scholar
  82. 80.
    Beighton P, Horan FT. Dominant inheritance in familial generalized articular hypermobility. J Bone Joint Surg Br. 1970;52B:145-147.Google Scholar
  83. 81.
    Horton WA, Collins DL, Desmet AA, Kennedy JA, Schimke RN. Familial joint instability syndrome. Am J Med Genet. 1980;6:221-228.PubMedGoogle Scholar
  84. 82.
    Horan FT, Beighton P. Recessive inheritance of generalized joint hypermobility. Rheumatol Rehabil. 1973;12:47-49.PubMedGoogle Scholar
  85. 83.
    Malfait F, AJ Hakim, De Paepe A, De Paepe A, Grahame R. The genetic basis of the joint hypermobility syndromes. Rheumatology. 2006;45:502-507.PubMedGoogle Scholar
  86. 84.
    Wynne-Davis R. Acetabular dysplasia and familial joint laxity, two etiologic factors in congenital dislocation of the hip. J Bone Joint Surg Br. 1970;52B:704-716.Google Scholar
  87. 85.
    Wynne-Davis R. A familial study of neonatal and late-diagnosis congenital dislocation of the hip. J Med Genet. 1970;7:315-333.Google Scholar
  88. 86.
    Bjerkreim I, van der Hagen CB. Congenital dislocation of the hip in Norway. Clin Genet. 1974;5:433-448.PubMedGoogle Scholar
  89. 87.
    Fredensborg N. Unilateral joint laxity in unilateral congenital dislocation of the hip. Int Orthop. 1978;2:177-178.Google Scholar
  90. 88.
    Smith BW, Coughlin MJ. The first metatarsocuneiform joint, hypermobility, and hallux valgus: what does it all mean? Foot Ankle Surg. 2008;14(3):138-141.PubMedGoogle Scholar
  91. 89.
    Jonsson H, Valtysdottir ST, Kjartansson O, Brekkan A. Hypermobility associated with osteoarthritis of the thumb base: a clinical and radiological subset of hand osteoarthritis. Ann Rheum Dis. 1996;55:540-543.PubMedGoogle Scholar
  92. 90.
    Chen HC, Shah SH, Li YJ, Stabler TV, Jordan JM, Kraus VB. Inverse association of general joint hypermobility with hand and knee osteoarthritis and serum cartilage oligometric matrix protein levels. Arthritis Rheum. 2008;58(12):3854-3864.PubMedGoogle Scholar
  93. 91.
    Grahame R, Edwards JC, Pitcher D, Gabell A, Harvey W. A clinical and echocardiographic study of patients with the hypermobility syndrome. Ann Rheum Dis. 1981;40:541-546.PubMedGoogle Scholar
  94. 92.
    Mishra MB, Ryan P, Atkinson P, et al. Extra-articular features of benign joint hypermobility syndrome. Br J Rheumatol. 1996;35:861-866.PubMedGoogle Scholar
  95. 93.
    Grahame R. Hypermobility: an important but often neglected area within rheumatology. Nat Clin Pract Rheumatol. 2008;4(10):522-524.PubMedGoogle Scholar
  96. 94.
    Lowe RM, Hashkes PJ. Growing pains: a noninflammatory pain syndrome of early childhood. Nat Clin Pract Rheumatol. 2008;4(10):542-549.PubMedGoogle Scholar
  97. 95.
    Viswanathan V, Khubchandani RP. Joint hypermobility and growing pains in school children. Clin Exp Rheumatol. 2008;26(5):962-966.PubMedGoogle Scholar
  98. 96.
    Beighton P. The Ehlers-Danlos syndrome. In: McKusick’s Heritable Disorders of Connective Tissue. 5th ed. St. Louis: Mosby; 1993:189-251.Google Scholar
  99. 97.
    Viljoen D, Beighton P. Marfan syndrome: a diagnostic dilemma. Clin Genet. 1990;37:417-422.PubMedGoogle Scholar
  100. 98.
    Svensson LG, Blackstone EH, Feng J, et al. Are Marfan syndrome and marfanoid patients distinguishable on long-term follow-up? Ann Thorac Surg. 2007;83(3):1067-1074.PubMedGoogle Scholar
  101. 98a.
    Halliday DJ, Hutchinson S, Lonie L, et al. Twelve novel FBN1 mutations in Marfan syndrome and Marfan related phenotypes test the feasibility of FBN1 mutation testing in clinical practice. J Med Genet. 2002;39:589-593.PubMedGoogle Scholar
  102. 99.
    De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyertitz RE. Revised diagnostic criteria for the Marfan syndrome. Am J Med Genet. 1996;62:417-426.PubMedGoogle Scholar
  103. 100.
    Dietz HC. Marfan syndrome: reviews at GeneTests-GeneClinics [databse online]. Available at, update 2005.
  104. 101.
    Weil UH. Osteogenesis imperfecta. Clin Orthop. 1981;159:6-10.PubMedGoogle Scholar
  105. 102.
    Engelbert RHH, van der Graaf Y, van Empelen R, Beemer FA, Helders PJM. Osteogenesis imperfecta in childhood: impairment and disability. Pediatrics. 1997;99:E3.PubMedGoogle Scholar
  106. 103.
    Antoniazzi F, Zamboni G, Lauriola S, Donadi L, Adami S, Tatò L. Early bisphosphonate treatment in infants with severe osteogenesis imperfecta. J Pediatr. 2006;149(2):174-179.PubMedGoogle Scholar
  107. 104.
    Viljoen D, Versfield G, Beighton P. Osteogenesis imperfecta with congenital joint contractures (Bruck syndrome). Clin Genet. 1989;36:122-126.PubMedGoogle Scholar
  108. 105.
    Steiner RD, Pepin MG, Byers PH. Osteogenesis imperfecta: reviews at Gene Tests-GeneClinics [database online]. Available at, 2005.
  109. 106.
    Teebi AS, Al Awadi SA, Marafie MJ, Bushnaq RA, Satyanath S. Osteoporosis-pseudoglioma syndrome with congenital heart disease: a new association. J Med Genet. 1988;25:32-36.PubMedGoogle Scholar
  110. 107.
    Biering A, Iversson T. Osteogenesis imperfecta associated with Ehlers-Danlos syndrome. Acta Paediatr. 1955;44:279-283.PubMedGoogle Scholar
  111. 108.
    Greenfield G, Romano A, Stein R, Goodman RM. Blue sclerae and keratoconus: key features of a distinct heritable disorder of connective tissue. Clin Genet. 1973;4:8-16.PubMedGoogle Scholar
  112. 109.
    Biglan AW, Brown SI, Johnson BL. Keratoglobus and blue sclerae. Am J Ophthalmol. 1977;83:225-233.PubMedGoogle Scholar
  113. 110.
    Robertson FW. Keratoconus and the Ehlers-Danlos syndrome; a new aspect keratoconus. Med J Aust. 1975;1:571-573.PubMedGoogle Scholar
  114. 111.
    Larsen LJ, Schottstaedt ER, Bost FC. Multiple congenital dislocations associated with characteristic facial abnormality. J Pediatr. 1950;37:574-581.PubMedGoogle Scholar
  115. 112.
    Martin Fernández-Mayoralas D, Fernández-Jaén A, Munoz-Jareno N, Calleja-Pérez B, San Antonio-Arce V, Martínez-Boniche H. Larsen syndrome: two reports of cases with spinal cord compromise. Rev Neurol. 2008;47(2):79-82.PubMedGoogle Scholar
  116. 113.
    Madera M, Crawford A, Mangano FT. Management of severe cervical kyphosis in a patient with Larsen syndrome: case report. J Neurosurg Pediatr. 2008;1(4):320-324.PubMedGoogle Scholar
  117. 114.
    Stanley D, Seymoor N. The Larsen syndrome occurring in four generations of one family. Int Orthop. 1985;8:267-272.PubMedGoogle Scholar
  118. 115.
    Clayton-Smith J, Donnai D. A further patient with the lethal type of Larsen syndrome. J Med Genet. 1988;25:499-500.PubMedGoogle Scholar
  119. 116.
    Hermanns P, Unger S, Rossi A, et al. Congenital joint dislocations caused by carbohydrate sulfotransferase 3 deficiency in recessive Larsen syndrome and humero-spinal dysostosis. Am J Hum Genet. 2008;82(6):1368-1374.PubMedGoogle Scholar
  120. 117.
    Desbuquois G, Grenier B, Michel J, Rossignot C. Nanisme chondrodystrophique avec ossification ararchique et polymalformations chez deux soeurs. Arch Fr Pediatr. 1966;23:573-587.Google Scholar
  121. 118.
    Hall BD. Lethality in Desbuquois dysplasia: three new cases. Pediatr Radiol. 2001;39:589-593.Google Scholar
  122. 119.
    Lloyd AR, Ragosta KG, Bryke CR, Hoo JJ. Desbuquois syndrome in three sisters with significantly different lengths of survival. Am J Med Genet A. 2006;140:125-135.Google Scholar
  123. 120.
    Beighton PH, Kozlowski K. Spondo-epi-metaphyseal dysplasia with joint laxity and severe progressive kyphoscoliosis. Skeletal Radiol. 1980;5:205-317.PubMedGoogle Scholar
  124. 121.
    Beighton P. Spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL). J Med Genet. 1994;31:136-140.PubMedGoogle Scholar
  125. 122.
    Torrington M, Beighton P. The ancestry of spondyloepimetaphyseal dysplasia with joint laxity (SEMDJL) in South Africa. Clin Genet. 1991;39:210-213.PubMedGoogle Scholar
  126. 123.
    Hall CM, Elcioglu NH, Shaw DG. A distinct form of Spondyloepimetaphyseal dysplasia with multiple dislocations. J Med Genet. 1998;35(7):566-572.PubMedGoogle Scholar
  127. 124.
    Smith W, Ji HP, Mouradian W, Pagon RA. Spondlyoepimetaphyseal dysplasia with joint laxity (SEMDJL): presentation in two unrelated patients in the United States. Am J Med Genet. 1999;86(3):245-252.PubMedGoogle Scholar
  128. 125.
    Sulko J, Kozlowski K. Spondyloepimetaphsyeal dysplasia with joint laxity, leptodactylic or Hall type: report of a case with normal face and literature review. J Pediatr Orthop B. 2008;17(6):323-327.PubMedGoogle Scholar
  129. 126.
    Hall CM, Elcioglu NH, MacDermot KD, Offiah AC, Winter RM. Spondyloepimetaphyseal dysplasia with multiple dislocations (Hall type): three further cases and evidence of autosomal dominant inheritance. J Med Genet. 2002;39(9):666-670.PubMedGoogle Scholar
  130. 127.
    Heselson NG, Cremin BJ, Beighton P. Pseudoachondroplasia, a report of 13 cases. Br J Radiol. 1977;50:473-482.PubMedGoogle Scholar
  131. 128.
    Vatanavicham N, Lachman RS, Rimoin DL. Multilayered patella: similar radiographic findings in pseudoachondroplasia and recessive multiple epiphyseal dysplasia. Am J Med Genet A. 2008;146(A):1682-1686.Google Scholar
  132. 129.
    Atinga M, Hamer AJ. Total knee replacements in a patient with the Morquio syndrome. J Bone Joint Surg Br. 2008;90(12):1631-1633.PubMedGoogle Scholar
  133. 130.
    Beighton P, Craig J. Atlanto-axial dislocation in the Morquio syndrome. J Bone Joint Surg Br. 1973;55B:478-480.Google Scholar
  134. 131.
    McKusick VA, Eldridge R, Hostetler JA, Egeland JA, Ruangwit U. Dwarfism in the Amish. II: cartilage-hair hypoplasia. Bull Johns Hopkins Hosp. 1965;116:285-326.PubMedGoogle Scholar
  135. 132.
    Makitie O, Sulisalo T, de la Chapelle A, Kaitila I. Cartilage-hair hypoplasia. J Med Genet. 1995;32:39-43.PubMedGoogle Scholar
  136. 133.
    Hall BD, Spranger J. Hypochondroplasia: clinical and radiological aspects in 39 cases. Radiology. 1979;133:95-100.PubMedGoogle Scholar
  137. 134.
    McKusick VA, Egeland JA, Eldridge R, Krusen DE. Dwarfism in the Amish: the Ellis-van Creveld syndrome. Bull Johns Hopkins Hosp. 1964;115:306-336.PubMedGoogle Scholar
  138. 135.
    Beighton P. Autosomal recessive inheritance in the mesomelic dwarfism of Campailla and Martinelli. Clin Genet. 1974;5:363-367.PubMedGoogle Scholar
  139. 136.
    Spranger J, Langer LO. Spondyloepiphyseal dysplasia congenital. Radiology. 1970;94:313-322.PubMedGoogle Scholar
  140. 137.
    Kannu P, Aftimos S, Mayne V, Donnan L, Savarirayan R. Metatropic dysplasia: clinical and radiographic findings in 11 patients demonstrating long-term natural history. Am J Med Genet A. 2007;143A:2512-2522.PubMedGoogle Scholar
  141. 138.
    Geneviève D, Le Merrer M, Feingold J, Munnich A, Maroteaux P, Cormier-Daire V. Revisiting metatropic dysplasia: presentation of a sseries of 19 novel patients and review of the literature. Am J Med Genet A. 2008;146A(8):992-996.PubMedGoogle Scholar
  142. 139.
    Currarino G. Hajdu-Cheney syndrome associated with serpentine fibulae and polycystic kidney disease. Pediatr Radiol. 2009;39(1):47-52.PubMedGoogle Scholar
  143. 140.
    Opitz JM, Smith JF, Santoro L. The FG syndromes: perspectives in 2008. Adv Pediatr. 2008;55:123-170.PubMedGoogle Scholar
  144. 141.
    Lyons MJ, Graham JM Jr, Neri G, et al. Clinical experience in the evaluation of 30 patients with a prior diagnosis of FG syndrome. J Med Genet. 2009;46(1):9-13.PubMedGoogle Scholar
  145. 142.
    Sayad CJ, Matheis P, Morrell DS. Hypotrichosis, bulbous nose, and cone-shaped epiphyses in an 8 year-old girl: trichorhinophalangeal syndrome type I. Pediatr Dermatol. 2008;25(5):557-558.Google Scholar
  146. 143.
    Aarskog D. A familial syndrome of short stature associated with facial dysplasia and genital anomalies. J Pediatr. 1970;77:856-861.PubMedGoogle Scholar
  147. 144.
    Zielinski JA, Pack LL. Bilateral anterior hip dislocation in a child with Aarskog syndrome: a case report. J Pediatr Orthop. 2008;28(7):729-732.PubMedGoogle Scholar
  148. 145.
    Young ID, Moore JR. Intrafamilial variation in Cohen syndrome. J Med Genet. 1987;28:488-492.Google Scholar
  149. 146.
    Saltzman CL, Herzenberg JE, Phillips WA, Hensinger RN, Hopwood NJ. Thick lips, bumpy tongue and slipped capital femoral epiphysis; a deadly combination. J Pediatr Orthop. 1988;8:219-222.PubMedGoogle Scholar
  150. 147.
    Pueschel SM, Scola FH, Pezzullo JC. A longitudinal study of atlanto-dens relationships in asymptomatic individuals with Down syndrome. Pediatrics. 1992;89:1194-1198.PubMedGoogle Scholar
  151. 148.
    Holtgrewe JL, Kalen V. Orthopaedic manifestations of the Lowe (oculocerebrorenal) syndrome. J Pediatr Orthop. 1986;6:165-171.PubMedGoogle Scholar
  152. 149.
    Herrera-Soto JA, Santiago-Cornier A, Segal LS, Ramirez N, Tamai J. The musculoskeletal manifestations of the Coffin-Lowry syndrome. J Pediatr Orthop. 2007;27(1):85-89.PubMedGoogle Scholar
  153. 150.
    Kawame H, Hannibal MC, Hudgins L, Pagon RA. Phenotypic spectrum and management issues in Kabuki syndrome. J Pediatr. 1999;134(4):480-485.PubMedGoogle Scholar
  154. 151.
    Sommer A. Photo essay-Sekel syndrome. Am J Med Genet C Semin Med Genet. 2007;145C(3):230-231.PubMedGoogle Scholar
  155. 152.
    Kääriäinen H, Ryöppy S, Norio R. RAPADILINO syndrome with radial and patellar aplasia/hypoplasia as main manifestations. Am J Med Genet. 1989;33(3):346-351.PubMedGoogle Scholar
  156. 153.
    Kivuva EC, Parker MJ, Cohen MC, Wagner BE, Sobey G. De Barsy syndrome: a review of the phenotype. Clin Dysmorphol. 2008;17:99-107.PubMedGoogle Scholar
  157. 154.
    Fleck BJ, Pandya A, Vanner L, Kerkering K, Bodurtha J. Coffin-Siris syndrome: review and presentation of new cases from a questionnaire. Am J Med Genet. 2001;99(1):1-7.PubMedGoogle Scholar
  158. 155.
    Snead MP, Yates JRN. Clinical and molecular genetics of Stickler syndrome. J Med Genet. 1999;3:192-196.Google Scholar

Copyright information

© Springer-Verlag London Limited 2012

Authors and Affiliations

  • Peter Beighton
    • 1
  • Rodney Grahame
    • 2
  • Howard Bird
    • 3
  1. 1.Department of Human GeneticsUniversity of Cape TownCape TownSouth Africa
  2. 2.Department of RheumatolgyUniversity College HospitalLondonUnited Kingdom
  3. 3.Department of Musculo–Skeletal MedicineUniversity of LeedsLeedsUnited Kingdom

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