Skeletal Dysplasias

  • Robert C. Olney
  • Michael B. Bober


The skeletal dysplasias (or more appropriately, the osteochondrodysplasias) are genetic disorders that affect the development of the skeletal and cartilaginous tissues. They are of interest to the pediatric endocrinologist not only because most have an impact on linear growth causing short stature but also for what these disorders teach us about the mechanisms and regulation of growth. Current and emerging treatments for specific syndromes are often managed by pediatric endocrinology.


Achondroplasia Acromesomelic dysplasia, type Maroteaux Arm span Bisphosphonates Blomstrand chondrodysplasia C-type natriuretic peptide Dwarfism Fibroblast growth factor receptor-3 Hypochondroplasia Jansen-type metaphyseal chondrodysplasia Léri-Weill osteodyschondrosteosis Madelung deformity Multiple epiphyseal dysplasia Natriuretic peptide receptor-B Osteochondrodysplasia Osteogenesis imperfecta Pamidronate Parathyroid hormone receptor Parathyroid hormone-related protein Recombinant human growth hormone Short-stature homeobox-containing gene SHOX Skeletal dysplasia Upper-to-lower segment ratio Zoledronic acid 


  1. 1.
    Bonafe L, Cormier-Daire V, Hall C, Lachman R, Mortier G, Mundlos S, et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet A. 2015 Dec;167A(12):2869–92.CrossRefGoogle Scholar
  2. 2.
    Falardeau F, Camurri MV, Campeau PM. Genomic approaches to diagnose rare bone disorders. Bone. 2017;102:5–14.CrossRefGoogle Scholar
  3. 3.
    Orioli IM, Castilla EE, Barbosa-Neto JG. The birth prevalence rates for the skeletal dysplasias. J Med Genet. 1986;23(4):328–32.CrossRefGoogle Scholar
  4. 4.
    Superti-Furga A, Unger S. Nosology and classification of genetic skeletal disorders: 2006 revision. Am J Med Genet A. 2007;143(1):1–18.CrossRefGoogle Scholar
  5. 5.
    McKusick VA. Heritable disorders of connective tissue. St. Louis: C.V. Mosby Company; 1972.Google Scholar
  6. 6.
    Hall JG, Allanson JE, Gripp KW, Slavotinek AM. Handbook of Physical Measurements. 2nd ed. Oxford: Oxford University Press; 2007.Google Scholar
  7. 7.
    Gripp KW, Slavotinek AM, Hall JG, Allanson JE. Handbook of physical measurements. 3rd ed. New York: Oxford University Press; 2013.CrossRefGoogle Scholar
  8. 8.
    Cole TJ. The LMS method for constructing normalized growth standards. Eur J Clin Nutr. 1990;44(1):45–60.PubMedGoogle Scholar
  9. 9.
    Loeys BL, Dietz HC, Braverman AC, Callewaert BL, De Backer J, Devereux RB, et al. The revised Ghent nosology for the Marfan syndrome. J Med Genet. 2010;47(7):476–85.CrossRefGoogle Scholar
  10. 10.
    Rimoin DL, Cohn D, Krakow D, Wilcox W, Lachman RS, Alanay Y. The skeletal dysplasias: clinical-molecular correlations. Ann N Y Acad Sci. 2007;1117:302–9.CrossRefGoogle Scholar
  11. 11.
    Zankl A, Jackson GC, Crettol LM, Taylor J, Elles R, Mortier GR, et al. Preselection of cases through expert clinical and radiological review significantly increases mutation detection rate in multiple epiphyseal dysplasia. Eur J Hum Genet. 2007;15(2):150–4.CrossRefGoogle Scholar
  12. 12.
    Jones KL. Smith's Recognizable Patterns of Human Malformation. 6th ed. Philadelphia: Elsevier Saunders; 2005.Google Scholar
  13. 13.
    Hunter AG, Bankier A, Rogers JG, Sillence D, Scott CI Jr. Medical complications of achondroplasia: a multicentre patient review. J Med Genet. 1998;35(9):705–12.CrossRefGoogle Scholar
  14. 14.
    Hoover-Fong J, McGready J, Schulze K, Alade AY, Scott CI. A height-for-age growth reference for children with achondroplasia: Expanded applications and comparison with original reference data. Am J Med Genet A. 2017;173(5):1226–30.CrossRefGoogle Scholar
  15. 15.
    Horton WA, Hall JG, Hecht JT. Achondroplasia. Lancet. 2007;370(9582):162–72.CrossRefGoogle Scholar
  16. 16.
    Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M, et al. Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia. Cell. 1994;78(2):335–42.CrossRefGoogle Scholar
  17. 17.
    Zhou ZQ, Ota S, Deng C, Akiyama H, Hurlin PJ. Mutant activated FGFR3 impairs endochondral bone growth by preventing SOX9 downregulation in differentiating chondrocytes. Hum Mol Genet. 2015;24(6):1764–73.CrossRefGoogle Scholar
  18. 18.
    Martinez-Frias ML, de Frutos CA, Bermejo E, Nieto MA. Review of the recently defined molecular mechanisms underlying thanatophoric dysplasia and their potential therapeutic implications for achondroplasia. Am J Med Genet A. 2010;152A(1):245–55.CrossRefGoogle Scholar
  19. 19.
    Laederich MB, Horton WA. Achondroplasia: pathogenesis and implications for future treatment. Curr Opin Pediatr. 2010;22(4):516–23.CrossRefGoogle Scholar
  20. 20.
    Trotter TL, Hall JG. Health supervision for children with achondroplasia. Pediatrics. 2005;116(3):771–83.CrossRefGoogle Scholar
  21. 21.
    Wilkin DJ, Szabo JK, Cameron R, Henderson S, Bellus GA, Mack ML, et al. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. Am J Hum Genet. 1998;63(3):711–6.CrossRefGoogle Scholar
  22. 22.
    Tanaka H, Kubo T, Yamate T, Ono T, Kanzaki S, Seino Y. Effect of growth hormone therapy in children with achondroplasia: growth pattern, hypothalamic-pituitary function, and genotype. Eur J Endocrinol. 1998;138(3):275–80.CrossRefGoogle Scholar
  23. 23.
    Ramaswami U, Rumsby G, Spoudeas HA, Hindmarsh PC, Brook CG. Treatment of achondroplasia with growth hormone: six years of experience. Pediatr Res. 1999;46(4):435–9.CrossRefGoogle Scholar
  24. 24.
    Hertel NT, Eklof O, Ivarsson S, Aronson S, Westphal O, Sipila I, et al. Growth hormone treatment in 35 prepubertal children with achondroplasia: a five-year dose-response trial. Acta Paediatr. 2005;94(10):1402–10.CrossRefGoogle Scholar
  25. 25.
    Miccoli M, Bertelloni S, Massart F. Height outcome of recombinant human growth hormone treatment in achondroplasia children: a metaanalysis. Horm Res Paediatr. 2016;86(1):27–34.CrossRefGoogle Scholar
  26. 26.
    Ozasa A, Komatsu Y, Yasoda A, Miura M, Sakuma Y, Nakatsuru Y, et al. Complementary antagonistic actions between C-type natriuretic peptide and the MAPK pathway through FGFR-3 in ATDC5 cells. Bone. 2005;36(6):1056–64.CrossRefGoogle Scholar
  27. 27.
    Yasoda A, Komatsu Y, Chusho H, Miyazawa T, Ozasa A, Miura M, et al. Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway. Nat Med. 2004;10(1):80–6.CrossRefGoogle Scholar
  28. 28.
    Yasoda A, Kitamura H, Fujii T, Kondo E, Murao N, Miura M, et al. Systemic administration of C-type natriuretic peptide as a novel therapeutic strategy for skeletal dysplasias. Endocrinology. 2009;150(7):3138–44.CrossRefGoogle Scholar
  29. 29.
    Wendt DJ, Dvorak-Ewell M, Bullens S, Lorget F, Bell SM, Peng J, et al. Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism. J Pharmacol Exp Ther. 2015;353(1):132–49.CrossRefGoogle Scholar
  30. 30.
    Matsushita M, Hasegawa S, Kitoh H, Mori K, Ohkawara B, Yasoda A, et al. Meclozine promotes longitudinal skeletal growth in transgenic mice with achondroplasia carrying a gain-of-function mutation in the FGFR3 gene. Endocrinology. 2015;156(2):548–54.CrossRefGoogle Scholar
  31. 31.
    Yamashita A, Morioka M, Kishi H, Kimura T, Yahara Y, Okada M, et al. Statin treatment rescues FGFR3 skeletal dysplasia phenotypes. Nature. 2014;513(7519):507–11.CrossRefGoogle Scholar
  32. 32.
    Komla-Ebri D, Dambroise E, Kramer I, Benoist-Lasselin C, Kaci N, Le Gall C, et al. Tyrosine kinase inhibitor NVP-BGJ398 functionally improves FGFR3-related dwarfism in mouse model. J Clin Invest. 2016;126(5):1871–84.CrossRefGoogle Scholar
  33. 33.
    Garcia S, Dirat B, Tognacci T, Rochet N, Mouska X, Bonnafous S, et al. Postnatal soluble FGFR3 therapy rescues achondroplasia symptoms and restores bone growth in mice. Sci Transl Med. 2013;5(203):203ra124.CrossRefGoogle Scholar
  34. 34.
    Bellus GA, McIntosh I, Smith EA, Aylsworth AS, Kaitila I, Horton WA, et al. A recurrent mutation in the tyrosine kinase domain of fibroblast growth factor receptor 3 causes hypochondroplasia. Nat Genet. 1995;10(3):357–9.CrossRefGoogle Scholar
  35. 35.
    Fredriks AM, van Buuren S, van Heel WJ, Dijkman-Neerincx RH, Verloove-Vanhorick SP, Wit JM. Nationwide age references for sitting height, leg length, and sitting height/height ratio, and their diagnostic value for disproportionate growth disorders. Arch Dis Child. 2005;90(8):807–12.CrossRefGoogle Scholar
  36. 36.
    Newman DE, Dunbar JC. Hypochondroplasia. J Can Assoc Radiol. 1975;26(2):95–103.PubMedGoogle Scholar
  37. 37.
    Xue Y, Sun A, Mekikian PB, Martin J, Rimoin DL, Lachman RS, et al. FGFR3 mutation frequency in 324 cases from the International Skeletal Dysplasia Registry. Mol Genet Genomic Med. 2014;2(6):497–503.CrossRefGoogle Scholar
  38. 38.
    Pinto G, Cormier-Daire V, Le Merrer M, Samara-Boustani D, Baujat G, Fresneau L, et al. Efficacy and safety of growth hormone treatment in children with hypochondroplasia: comparison with an historical cohort. Horm Res Paediatr. 2014;82(6):355–63.CrossRefGoogle Scholar
  39. 39.
    Tanaka N, Katsumata N, Horikawa R, Tanaka T. The comparison of the effects of short-term growth hormone treatment in patients with achondroplasia and with hypochondroplasia. Endocr J. 2003;50(1):69–75.CrossRefGoogle Scholar
  40. 40.
    Kanazawa H, Tanaka H, Inoue M, Yamanaka Y, Namba N, Seino Y. Efficacy of growth hormone therapy for patients with skeletal dysplasia. J Bone Miner Metab. 2003;21(5):307–10.CrossRefGoogle Scholar
  41. 41.
    Key LL Jr, Gross AJ. Response to growth hormone in children with chondrodysplasia. J Pediatr. 1996;128(5 Pt 2):S14–7.CrossRefGoogle Scholar
  42. 42.
    Appan S, Laurent S, Chapman M, Hindmarsh PC, Brook CG. Growth and growth hormone therapy in hypochondroplasia. Acta Paediatr Scand. 1990;79(8–9):796–803.CrossRefGoogle Scholar
  43. 43.
    Massart F, Miccoli M, Baggiani A, Bertelloni S. Height outcome of short children with hypochondroplasia after recombinant human growth hormone treatment: a meta-analysis. Pharmacogenomics. 2015;16(17):1965–73.CrossRefGoogle Scholar
  44. 44.
    Yasui N, Kawabata H, Kojimoto H, Ohno H, Matsuda S, Araki N, et al. Lengthening of the lower limbs in patients with achondroplasia and hypochondroplasia. Clin Orthop Relat Res. 1997;344:298–306.CrossRefGoogle Scholar
  45. 45.
    Kitoh H, Kitakoji T, Tsuchiya H, Katoh M, Ishiguro N. Distraction osteogenesis of the lower extremity in patients with achondroplasia/hypochondroplasia treated with transplantation of culture-expanded bone marrow cells and platelet-rich plasma. J Pediatr Orthop. 2007;27(6):629–34.CrossRefGoogle Scholar
  46. 46.
    Unger S, Bonafe L, Superti-Furga A. Multiple epiphyseal dysplasia: clinical and radiographic features, differential diagnosis and molecular basis. Best Pract Res Clin Rheumatol. 2008;22(1):19–32.CrossRefGoogle Scholar
  47. 47.
    Ross JL, Scott C Jr, Marttila P, Kowal K, Nass A, Papenhausen P, et al. Phenotypes associated with SHOX deficiency. J Clin Endocrinol Metab. 2001;86(12):5674–80.CrossRefGoogle Scholar
  48. 48.
    Ross JL, Kowal K, Quigley CA, Blum WF, Cutler GB Jr, Crowe B, et al. The phenotype of short stature homeobox gene (SHOX) deficiency in childhood: contrasting children with Leri-Weill dyschondrosteosis and Turner syndrome. J Pediatr. 2005;147(4):499–507.CrossRefGoogle Scholar
  49. 49.
    Cook PA, Yu JS, Wiand W, Lubbers L, Coleman CR, Cook AJ, et al. Madelung deformity in skeletally immature patients: morphologic assessment using radiography, CT, and MRI. J Comput Assist Tomogr. 1996;20(4):505–11.CrossRefGoogle Scholar
  50. 50.
    Blanco ME, Perez-Cabrera A, Kofman-Alfaro S, Zenteno JC. Clinical and cytogenetic findings in 14 patients with Madelung anomaly. Orthopedics. 2005;28(3):315–9.PubMedGoogle Scholar
  51. 51.
    Rao E, Weiss B, Fukami M, Rump A, Niesler B, Mertz A, et al. Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome [see comments]. Nat Genet. 1997;16(1):54–63.CrossRefGoogle Scholar
  52. 52.
    Ellison JW, Wardak Z, Young MF, Gehron RP, Laig-Webster M, Chiong W. PHOG, a candidate gene for involvement in the short stature of Turner syndrome. Hum Mol Genet. 1997;6(8):1341–7.CrossRefGoogle Scholar
  53. 53.
    Chen J, Wildhardt G, Zhong Z, Roth R, Weiss B, Steinberger D, et al. Enhancer deletions of the SHOX gene as a frequent cause of short stature: the essential role of a 250 kb downstream regulatory domain. J Med Genet. 2009;46(12):834–9.CrossRefGoogle Scholar
  54. 54.
    Munns CJ, Haase HR, Crowther LM, Hayes MT, Blaschke R, Rappold G, et al. Expression of SHOX in human fetal and childhood growth plate. J Clin Endocrinol Metab. 2004;89(8):4130–5.CrossRefGoogle Scholar
  55. 55.
    Spranger S, Schiller S, Jauch A, Wolff K, Rauterberg-Ruland I, Hager D, et al. Leri-Weill syndrome as part of a contiguous gene syndrome at Xp22.3. Am J Med Genet. 1999;83(5):367–71.CrossRefGoogle Scholar
  56. 56.
    Quigley CA, Crowe BJ, Anglin DG, Chipman JJ. Growth hormone and low dose estrogen in Turner syndrome: results of a United States multi-center trial to near-final height. J Clin Endocrinol Metab. 2002;87(5):2033–41.CrossRefGoogle Scholar
  57. 57.
    Blum WF, Cao D, Hesse V, Fricke-Otto S, Ross JL, Jones C, et al. Height gains in response to growth hormone treatment to final height are similar in patients with SHOX deficiency and Turner syndrome. Horm Res. 2009;71(3):167–72.CrossRefGoogle Scholar
  58. 58.
    Richmond E, Rogol AD. Current indications for growth hormone therapy for children and adolescents. Endocr Dev. 2010;18:92–108.CrossRefGoogle Scholar
  59. 59.
    Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979;16(2):101–16.CrossRefGoogle Scholar
  60. 60.
    Steiner RD, Pepin MG, Byers PH. Osteogenesis imperfecta. In: Pagon RA, Bird TB, Dolan CR, Stephens K, editors. GeneReviews (Internet). Seattle: University of Washington; 2011.Google Scholar
  61. 61.
    Rohrbach M, Giunta C. Recessive osteogenesis imperfecta: clinical, radiological, and molecular findings. Am J Med Genet C Semin Med Genet. 2012;160C(3):175–89.CrossRefGoogle Scholar
  62. 62.
    Van Dijk FS, Sillence DO. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A. 2014;164A(6):1470–81.CrossRefGoogle Scholar
  63. 63.
    Patel RM, Nagamani SC, Cuthbertson D, Campeau PM, Krischer JP, Shapiro JR, et al. A cross-sectional multicenter study of osteogenesis imperfecta in North America - results from the linked clinical research centers. Clin Genet. 2015;87(2):133–40.CrossRefGoogle Scholar
  64. 64.
    Bardai G, Moffatt P, Glorieux FH, Rauch F. DNA sequence analysis in 598 individuals with a clinical diagnosis of osteogenesis imperfecta: diagnostic yield and mutation spectrum. Osteoporos Int. 27(12):3607–13.CrossRefGoogle Scholar
  65. 65.
    Trejo P, Rauch F. Osteogenesis imperfecta in children and adolescents-new developments in diagnosis and treatment. Osteoporos Int. 2016;27(12):3427–37.CrossRefGoogle Scholar
  66. 66.
    Thomas IH, DiMeglio LA. Advances in the classification and treatment of osteogenesis imperfecta. Curr Osteoporos Rep. 2016;14(1):1–9.CrossRefGoogle Scholar
  67. 67.
    Montpetit K, Palomo T, Glorieux FH, Fassier F, Rauch F. Multidisciplinary treatment of severe osteogenesis imperfecta: functional outcomes at skeletal maturity. Arch Phys Med Rehabil. 2015;96(10):1834–9.CrossRefGoogle Scholar
  68. 68.
    Bregou BA, Aubry-Rozier B, Bonafe L, Laurent-Applegate L, Pioletti DP, Zambelli PY. Osteogenesis imperfecta: from diagnosis and multidisciplinary treatment to future perspectives. Swiss Med Wkly. 2016;146:w14322.Google Scholar
  69. 69.
    Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med. 1998;339(14):947–52.CrossRefGoogle Scholar
  70. 70.
    Zeitlin L, Rauch F, Plotkin H, Glorieux FH. Height and weight development during four years of therapy with cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta types I, III, and IV. Pediatrics. 2003;111(5 Pt 1):1030–6.CrossRefGoogle Scholar
  71. 71.
    Falk MJ, Heeger S, Lynch KA, DeCaro KR, Bohach D, Gibson KS, et al. Intravenous bisphosphonate therapy in children with osteogenesis imperfecta. Pediatrics. 2003;111(3):573–8.CrossRefGoogle Scholar
  72. 72.
    Alharbi M, Pinto G, Finidori G, Souberbielle JC, Guillou F, Gaubicher S, et al. Pamidronate treatment of children with moderate-to-severe osteogenesis imperfecta: a note of caution. Horm Res. 2009;71(1):38–44.PubMedGoogle Scholar
  73. 73.
    Rijks EB, Bongers BC, Vlemmix MJ, Boot AM, van Dijk AT, Sakkers RJ, et al. Efficacy and safety of bisphosphonate therapy in children with osteogenesis imperfecta: a systematic review. Horm Res Paediatr. 2015;84(1):26–42.CrossRefGoogle Scholar
  74. 74.
    Dwan K, Phillipi CA, Steiner RD, Basel D. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2014;7:CD005088.Google Scholar
  75. 75.
    Rauch F. Bisphosphonate treatment and related agents in children. In: Shapiro JR, Byers PH, Glorieux FH, Sponsellor PD, editors. Osteogenesis imperfecta: a translational approach to Brittle Bone Disease. New York: Academic Press; 2014. p. 501–7.CrossRefGoogle Scholar
  76. 76.
    Ngan KK, Bowe J, Goodger N. The risk of bisphosphonate-related osteonecrosis of the jaw in children. A case report and literature review. Dent Update. 2013;40(9):733–8.CrossRefGoogle Scholar
  77. 77.
    Hennedige AA, Jayasinghe J, Khajeh J, Macfarlane TV. Systematic review on the incidence of bisphosphonate related osteonecrosis of the jaw in children diagnosed with osteogenesis imperfecta. J Oral Maxillofac Res. 2013;4(4):e1.PubMedGoogle Scholar
  78. 78.
    Barros ER, Saraiva GL, de Oliveira TP, Lazaretti-Castro M. Safety and efficacy of a 1-year treatment with zoledronic acid compared with pamidronate in children with osteogenesis imperfecta. J Pediatr Endocrinol Metab. 2012;25(5–6):485–91.PubMedGoogle Scholar
  79. 79.
    Vuorimies I, Toiviainen-Salo S, Hero M, Makitie O. Zoledronic acid treatment in children with osteogenesis imperfecta. Horm Res Paediatr. 2011;75(5):346–53.CrossRefGoogle Scholar
  80. 80.
    Rauch F, Cornibert S, Cheung M, Glorieux FH. Long-bone changes after pamidronate discontinuation in children and adolescents with osteogenesis imperfecta. Bone. 2007;40(4):821–7.CrossRefGoogle Scholar
  81. 81.
    Marini JC, Bordenick S, Heavner G, Rose S, Hintz R, Rosenfeld R, et al. The growth hormone and somatomedin axis in short children with osteogenesis imperfecta. J Clin Endocrinol Metab. 1993;76(1):251–6.PubMedGoogle Scholar
  82. 82.
    Antoniazzi F, Monti E, Venturi G, Franceschi R, Doro F, Gatti D, et al. GH in combination with bisphosphonate treatment in osteogenesis imperfecta. Eur J Endocrinol. 2010;163(3):479–87.CrossRefGoogle Scholar
  83. 83.
    Marini JC, Hopkins E, Glorieux FH, Chrousos GP, Reynolds JC, Gundberg CM, et al. Positive linear growth and bone responses to growth hormone treatment in children with types III and IV osteogenesis imperfecta: high predictive value of the carboxyterminal propeptide of type I procollagen. J Bone Miner Res. 2003;18(2):237–43.CrossRefGoogle Scholar
  84. 84.
    Kruse K, Schutz C. Calcium metabolism in the Jansen type of metaphyseal dysplasia. Eur J Pediatr. 1993;152(11):912–5.CrossRefGoogle Scholar
  85. 85.
    Schipani E, Kruse K, Juppner H. A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science. 1995;268:98–100.CrossRefGoogle Scholar
  86. 86.
    Blomstrand S, Claesson I, Save-Soderbergh J. A case of lethal congenital dwarfism with accelerated skeletal maturation. Pediatr Radiol. 1985;15(2):141–3.CrossRefGoogle Scholar
  87. 87.
    Oostra RJ, van der Harten JJ, Rijnders WP, Scott RJ, Young MP, Trump D. Blomstrand osteochondrodysplasia: three novel cases and histological evidence for heterogeneity. Virchows Arch. 2000;436(1):28–35.CrossRefGoogle Scholar
  88. 88.
    Loshkajian A, Roume J, Stanescu V, Delezoide AL, Stampf F, Maroteaux P. Familial Blomstrand chondrodysplasia with advanced skeletal maturation: further delineation. Am J Med Genet. 1997;71(3):283–8.CrossRefGoogle Scholar
  89. 89.
    Jobert AS, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M, et al. Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. J Clin Invest. 1998;102(1):34–40.CrossRefGoogle Scholar
  90. 90.
    Kronenberg HM. PTHrP and skeletal development. Ann N Y Acad Sci. 2006;1068:1–13.CrossRefGoogle Scholar
  91. 91.
    Alvarez J, Sohn P, Zeng X, Doetschman T, Robbins DJ, Serra R. TGFbeta2 mediates the effects of hedgehog on hypertrophic differentiation and PTHrP expression. Development. 2002;129(8):1913–24.PubMedGoogle Scholar
  92. 92.
    Minina E, Wenzel HM, Kreschel C, Karp S, Gaffield W, McMahon AP, et al. BMP and Ihh/PTHrP signaling interact to coordinate chondrocyte proliferation and differentiation. Development. 2001;128(22):4523–34.PubMedGoogle Scholar
  93. 93.
    Maroteaux P, Martinelli B, Campailla E. Acromesomelic dwarfism. Presse Med. 1971;79(42):1839–42.PubMedGoogle Scholar
  94. 94.
    Langer LO Jr, Beals RK, Solomon IL, Bard PA, Bard LA, Rissman EM, et al. Acromesomelic dwarfism: manifestations in childhood. Am J Med Genet. 1977;1(1):87–100.CrossRefGoogle Scholar
  95. 95.
    Bartels CF, Bukulmez H, Padayatti P, Rhee DK, Ravenswaaij-Arts C, Pauli RM, et al. Mutations in the Transmembrane Natriuretic Peptide Receptor NPR-B Impair Skeletal Growth and Cause Acromesomelic Dysplasia. Type Maroteaux Am J Hum Genet. 2004;75(1):27–34.CrossRefGoogle Scholar
  96. 96.
    Olney RC, Bukulmez H, Bartels CF, Prickett TC, Espiner EA, Potter LR, et al. Heterozygous mutations in natriuretic peptide receptor-B (NPR2) are associated with short stature. J Clin Endocrinol Metab. 2006;91(2):1229–32.CrossRefGoogle Scholar
  97. 97.
    Olney RC. C-type natriuretic peptide in growth: a new paradigm. Growth Hormon IGF Res. 2006;16(Suppl A):S6–14.CrossRefGoogle Scholar
  98. 98.
    Borrelli P, Fasanelli S, Marini R. Acromesomelic dwarfism in a child with an interesting family history. Pediatr Radiol. 1983;13(3):165–8.CrossRefGoogle Scholar
  99. 99.
    Hisado-Oliva A, Garre-Vazquez AI, Santaolalla-Caballero F, Belinchon A, Barreda-Bonis AC, Vasques GA, et al. Heterozygous NPR2 Mutations Cause Disproportionate Short Stature, Similar to Leri-Weill Dyschondrosteosis. J Clin Endocrinol Metab. 2015;100(8):E1133–42.CrossRefGoogle Scholar
  100. 100.
    Wang SR, Jacobsen CM, Carmichael H, Edmund AB, Robinson JW, Olney RC, et al. Heterozygous mutations in natriuretic peptide receptor-B (NPR2) gene as a cause of short stature. Hum Mutat. 2015;36(4):474–81.CrossRefGoogle Scholar
  101. 101.
    Harvey W, Willis R. Sydenham Society. The works of William Harvey. Printed for the Sydenham Society; 1847.Google Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Endocrinology, Diabetes and MetabolismNemours Children’s Specialty CareJacksonvilleUSA
  2. 2.Skeletal Dysplasia Program, Medical GeneticsNemours/A.I. du Pont Hospital for ChildrenWilmingtonUSA

Personalised recommendations