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Blomstrand’s Chondrodysplasia

  • Francesca Giusti
  • Luisella Cianferotti
  • Laura Masi
  • Maria Luisa BrandiEmail author
Chapter

Abstract

Blomstrand’s chondrodysplasia (BOCD) (OMIM 215045) is an autosomal recessive disorder caused by inactivating mutations in the PTH/PTHrP receptor (PTH1R), leading to severe developmental abnormalities. This polymalformative syndrome, due to advanced skeletal maturation, is characterized by very short limbs and dwarfism; a narrow thorax; facial anomalies such as macroglossia, micrognathia, and depressed nasal bridge; as well as polyhydramnios, hydrops fetalis, hypoplastic lungs, protruding eyes showing cataracts, and internal malformation such as preductal aortic coarctation, possibly associated with functional hypoparathyroidism (hypocalcemia and hyperphosphatemia) with inappropriately high PTH levels, indicating a syndrome of PTH resistance. The disease can lead to fetal death or can present at birth. Diagnosis can be made as early as 12–13 gestational weeks by transvaginal ultrasound. The disorder is lethal and there is no treatment to date.

Keywords

PTH1R PTH/PTHrP receptor Dwarfism Hypoparathyroidism 

References

  1. 1.
    Loshkajian A, Roume J, Stanescu V, Delezoide A, Stampf F, Maroteaux P (1997) Familial Blomstrand chondrodysplasia with advanced skeletal maturation: further delineation. Am J Med Genet 71:283–288CrossRefPubMedGoogle Scholar
  2. 2.
    Jobert A-S, Zhang P, Couvineau A, Bonaventure J, Roume J, Le Merrer M, Silve C (1998) Absence of functional receptors for parathyroid hormone and parathyroid hormone-related peptide in Blomstrand chondrodysplasia. J Clin Invest 102:34–40CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Jupper H, Schipani E (1997) The parathyroid hormone/parathyroid hormone-related peptide receptor in Jansen’s metaphyseal chondrodysplasia. Curr Opin Endocrinol Diabetes 4:433–442CrossRefGoogle Scholar
  4. 4.
    Charrow J, Poznanski AK (1984) The Jansen type of metaphyseal chondrodysplasia: confirmation of dominant inheritance and review of radiographic manifestations in the newborn and adult. Am J Med Genet 18:321–327CrossRefPubMedGoogle Scholar
  5. 5.
    Couvineau A, Wouters V, Bertrand G, Rouyer C, Gerard B, Boon LM, Grandchamp B, Vikkula M, Silve C (2008) PTH1R mutations associated with Ollier disease result in receptor loss of function. Hum Mol Genet 17:2766–2775CrossRefPubMedCentralPubMedGoogle Scholar
  6. 6.
    Duchatelet S, Ostergaard E, Cortes D, Lemainque A, Julier C (2005) Recessive mutations in PTH1R cause contrasting skeletal dysplasias in Eiken and Blomstrand syndromes. Hum Mol Genet 14:1–5CrossRefPubMedGoogle Scholar
  7. 7.
    Decker E, Stellzig-Eisenhauer A, Fiebig BS, Rau C, Kress W, Saar K, Ruschendorf F, Hubner N, Grimm T, Weber BHF (2008) PTH1R loss-of-function mutations in familial, nonsyndromic primary failure of tooth eruption. Am J Hum Genet 83:781–786CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Wysolmerski JJ, Cormier S, Philbrick WM, Dann P, Zhang J-P, Roume J, Delezoide A-L, Silve C (2001) Absence of functional type 1 parathyroid hormone (PTH)/PTH-related protein receptors in humans is associated with abnormal breast development and tooth impaction. J Clin Endocrinol Metab 86:1788–1794PubMedGoogle Scholar
  9. 9.
    Blomstrand S, Claesson I, Save-Soderbergh J (1985) A case of lethal congenital dwarfism with accelerated skeletal maturation. Pediatr Radiol 15:141–143CrossRefPubMedGoogle Scholar
  10. 10.
    Spranger J, Maroteaux P (1990) The lethal osteochondrodysplasias. In: Harris H, Hirschhorn K (eds) Advances in human genetics. Plenum Press (pub.), New York, pp 1–103CrossRefGoogle Scholar
  11. 11.
    Young ID, Zuccollo JM, Broderick NJ (1993) A lethal skeletal dysplasia with generalised sclerosis and advanced skeletal maturation: Blomstrand chondrodysplasia? J Med Genet 30:155–157CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Leroy JG, Keersmaeckers G, Coppens M, Dumon JE, Roels H (1996) Blomstrand lethal osteochondrodysplasia. Am J Med Genet 63:84–89CrossRefPubMedGoogle Scholar
  13. 13.
    Den Hollander NS, van der Harten HJ, Vermeij-Keers C, Niermeijer MF, Wladimiroff JW (1997) First-trimester diagnosis of Blomstrand lethal osteochondrodysplasia. Am J Med Genet 73:345–350CrossRefGoogle Scholar
  14. 14.
    Oostra RJ, van der Harten HJ, Rijnders WPHA, Scott RJ, Young MPA, Trump D (2000) Blomstrand osteochondrodysplasia: three novel cases and histological evidence for heterogeneity. Virchows Arch 436:28–35CrossRefPubMedGoogle Scholar
  15. 15.
    Mannstadt M, Jüppner H, Gardella TJ (1999) Receptors for PTH and PTHrP: their biological importance and functional properties. Am J Physiol 277(5 Pt 2):F665–F675PubMedGoogle Scholar
  16. 16.
    Offermanns S, Iida-Klein A, Segre GV, Simon MI (1996) G alpha q family members couple parathyroid hormone (PTH)/PTH-related peptide and calcitonin receptors to phospholipase C in COS-7 cells. Mol Endocrinol 10(5):566–574PubMedGoogle Scholar
  17. 17.
    Karaplis AC, Luz A, Glowacki J, Bronson RT, Tybulewicz VLJ, Kronenberg HM, Mulligan RC (1994) Lethal skeletal dysplasia from targeted disruption of the parathyroid hormone-related peptide gene. Genes Dev 8:277–289CrossRefPubMedGoogle Scholar
  18. 18.
    Weir EC, Philbrick WM, Amling M, Neff LA, Baron R, Broadus AE (1996) Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation. Proc Natl Acad Sci U S A 93:10240–10245CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Lanske B, Karaplis AC, Lee K, Luz A, Vortkamp A, Pirro A, Karperien M, Defize LH, Ho C, Mulligan RC, Abou-Samra AB, Juppner H, Segre GV, Kronenberg HM (1996) PTH/PTHrP receptor in early development and Indian hedgehog-regulated bone growth. Science 273:663–666CrossRefPubMedGoogle Scholar
  20. 20.
    Karaplis AC, He B, Nguyen MT, Young ID, Semeraro D, Ozawa H, Amizuka N (1998) Inactivating mutation in the human parathyroid hormone receptor type 1 gene in Blomstrand chondrodysplasia. Endocrinology 139:5255–5258CrossRefPubMedGoogle Scholar
  21. 21.
    Karperien M, van der Harten HJ, van Schooten R, Farih-Sips H, Den Hollander NS, Kneppers SL, Nijweide P, Papapoulos SE, Lowik CW (1999) A frame-shift mutation in the type I parathyroid hormone (PTH)/PTH-related peptide receptor causing Blomstrand lethal osteochondrodysplasia. J Clin Endocrinol Metab 84:3713–3720CrossRefPubMedGoogle Scholar
  22. 22.
    Hoogendam J, Farih-Sips H, Wynaendts LC, Lowik CWGM, Wit JM, Karperien M (2007) Novel mutations in the parathyroid hormone (PTH)/PTH-related peptide receptor type 1 causing Blomstrand osteochondrodysplasia types I and II. J Clin Endocrinol Metab 92:1088–1095CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Italia 2015

Authors and Affiliations

  • Francesca Giusti
    • 1
  • Luisella Cianferotti
    • 2
  • Laura Masi
    • 2
  • Maria Luisa Brandi
    • 1
    Email author
  1. 1.Bone Metabolic Diseases Unit, Department of Surgery and Translational MedicineUniversity of FlorenceFlorenceItaly
  2. 2.Department of Surgery and Translational MedicineUniversity of FlorenceFlorenceItaly

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