Advertisement

The phenotype of fibrodysplasia ossificans progressiva

  • Frederick S. KaplanEmail author
  • David L. Glaser
  • Eileen M. Shore
  • Gregory K. Deirmengian
  • Rishi Gupta
  • Patricia Delai
  • Rolf Morhart
  • Roger Smith
  • Martine Le Merrer
  • John G. Rogers
  • J. Michael Connor
  • Joseph A. Kitterman
Fibrodysplasia Ossificans Progressiva

Abstract

The phenotype of fibrodysplasia ossificans progressiva (FOP) includes two defining features: congenital malformation of the great toes and progressive heterotopic ossification in characteristic anatomic patterns. Additional common features include proximal medial tibial osteochondromas, orthotopic fusions of the posterior elements of the cervical spine, broad short femoral necks, and conductive hearing loss. The FOP phenotype supports that the primary molecular pathology involves the bone morphogenetic protein (BMP)-signaling pathway directly or a BMP-interacting pathway.

Key words

Fibrodysplasia ossificans progressiva (FOP) bone morphogenetic protein (BMP)-signaling pathway heterotopic ossification malformed great toes 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Connor JM, Evans DA. 1982 Fibrodysplasia ossificans progressiva. The clinical features and natural history of 34 patients. J Bone Joint Surg Br 64:76–83.PubMedGoogle Scholar
  2. 2.
    Kaplan FS, Shore EM, Connor JM. 2002 Fibrodysplasia ossificans progressiva (FOP). In: Royce PM, Steinmann B, Connective Tissue and Its Heritable Disorders: Molecular, Genetic, and Medical Aspects 2nd Ed., Wiley-Liss, John Wiley & Sons, Inc., New York, pp. 827–840.Google Scholar
  3. 3.
    McKusick VA. 1972 Heritable Disorders of Connective Tissue. C. V. Mosby Company, St. Louis, MO.Google Scholar
  4. 4.
    Kitterman JA, Kantanie S, Rocke DM, Kaplan FS. 2005 Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva. Pediatrics, in press.Google Scholar
  5. 5.
    Smith R. 1998 Fibrodysplasia ossificans (myositis) progressiva (FOP). Clin Orthop 346:7–14.PubMedGoogle Scholar
  6. 6.
    Cohen RB, Hahn GV, Tabas J, et al. 1993 The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. J Bone Joint Surg 75-A:215–219.Google Scholar
  7. 7.
    Rocke DM, Zasloff M, Peeper J, Cohen RB, Kaplan FS. 1994 Age and joint-specific risk of initial heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. Clin Orthop 301:243–248.PubMedGoogle Scholar
  8. 8.
    Kaplan FS, Tabas J, Gannon FH, Finkel G, Hahn GV, Zasloff MA. 1993 The histopathology of fibrodysplasia ossificans progressiva: an endochondral process. J Bone Joint Surg 75-A:220–230.Google Scholar
  9. 9.
    Glaser DL, Rocke DM, Kaplan FS. 1998 Catastrophic falls in patients who have fibrodysplasia ossificans progressiva. Clin Orthop 346:110–116.PubMedGoogle Scholar
  10. 10.
    Luchetti W, Cohen RB, Hahn GV, Rocke DM, Helpin M, Zasloff M, Kaplan FS. 1996 Severe restriction in jaw movement after route injection of local anesthetic in patients who have fibrodysplasia ossificans progressiva. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 81:21–25.PubMedCrossRefGoogle Scholar
  11. 11.
    Lachoney TF, Cohen RB, Rocke DM, Zasloff MA, Kaplan FS. 1995 Permanent heterotopic ossification at the injection site after diphtheria-tetanus-pertussis immunizations in children who have fibrodysplasia ossificans progressiva. J Pediatrics 126:762–764.CrossRefGoogle Scholar
  12. 12.
    Scarlett RF, Rocke DM, Kantanie S, Patel JB, Shore EM, Kaplan FS. 2004 Influenza-like viral illnesses and flare-ups of fibrodysplasia ossificans progressiva (FOP). Clin Orthop 423:275–279.PubMedCrossRefGoogle Scholar
  13. 13.
    Moriatis JM, Gannon FH, Shore EM, Bilker W, Zasloff MA, Kaplan FS. 1997 Limb swelling in patients who have fibrodysplasia ossificans progressiva. Clin Orthop 336:247–253.PubMedCrossRefGoogle Scholar
  14. 14.
    Shah PB, Zasloff MA, Drummond D, Kaplan FS. 1994 Spinal deformity in patients who have fibrodysplasia ossificans progressiva. J Bone Joint Surg 76-A:1442–1450.Google Scholar
  15. 15.
    Kaplan FS, McCluskey W, Hahn G, Tabas J, Muenke M, Zasloff MA. 1993 Genetic transmission of fibrodysplasia ossificans progressiva. J Bone Joint Surg 75-A:1214–1220.Google Scholar
  16. 16.
    Janoff HB, Tabas JA, Shore EM, et al. 1995 Mild expression of fibrodysplasia ossificans progressiva. J Rheumatol 22:976–978.PubMedGoogle Scholar
  17. 17.
    Virdi AS, Shore EM, Oreffo ROC, et al. 1999 Phenotypic and molecular heterogeneity in fibrodysplasia ossificans progressiva. Calcif Tissue Int 65:250–255.PubMedCrossRefGoogle Scholar
  18. 18.
    Schaffer AA, Kaplan FS, Tracy MR, et al. 2005 Developmental anomalies of the cervical spine in patients with fibrodysplasia ossificans progressiva are distinctly different from those in patients with Klippel-Feil syndrome: clues from the BMP signaling pathway. Spine 30: 1379–1385.PubMedCrossRefGoogle Scholar
  19. 19.
    Renton P, Parkin SR, Stamp TCB. 1982 Abnormal temporomandibular joints in fibrodysplasia ossificans progressiva. Br J Oral Surg 20:31–38.PubMedCrossRefGoogle Scholar
  20. 20.
    Nussbaum BL, O'Hara I, Kaplan FS. 1996 Fibrodysplasia ossificans progressiva: report of a case with guidelines for pediatric dental and anesthetic management. J Dentistry Children 63:448–450.Google Scholar
  21. 21.
    Janoff HB, Zasloff MA, Kaplan FS. 1996 Submandibular swelling in patients with fibrodysplasia ossificans progressiva. Otolaryngol Head Neck Surg 114:599–604.PubMedCrossRefGoogle Scholar
  22. 22.
    Kaplan FS, Strear CM, Zasloff MA. 1994 Radiographic and scintigraphic features of modeling and remodeling in the heterotopic skeleton of patients who have fibrodysplasia ossificans progressiva. Clin Orthop 304:238–247.PubMedGoogle Scholar
  23. 23.
    Mahboubi S, Glaser DL, Shore EM, Kaplan FS. 2001 Fibrodysplasia ossificans progressiva. Pediatr Radiol 31:307–314.PubMedCrossRefGoogle Scholar
  24. 24.
    Levy CE, Lash AT, Janoff HB, Kaplan FS. 1999 Conductive hearing loss in individuals with fibrodysplasia ossificans progressive. Am J Audiol 8:29–33.PubMedCrossRefGoogle Scholar
  25. 25.
    Einhorn TA, Kaplan FS. Traumatic fractures of heterotopic bone in patients who have fibrodysplasia ossificans progressiva. 1994 Clin Orthop 308:173–177.PubMedGoogle Scholar
  26. 26.
    Kaplan KS, Glaser DL, Shore EM. 2003 Fibrodysplasia (myositis) ossificans progressiva. In: Favus MJ, ed.: Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism—5th Ed. The American Society for Bone and Mineral Research, Washington, DC, pp. 513–516.Google Scholar
  27. 27.
    Kaplan FS, Shore EM, Glaser DL, Emerson S. and the International Clinical Consortium on Fibrodysplasia Ossificans Progressiva. 2005. The medical management of fibrodysplasia ossificans progressiva: current treatment considerations. Clin Proc Intl Clin Consort FOP 1:1–72.Google Scholar
  28. 28.
    Lutwak L. 1964 Myositis ossificans progressiva: mineral, metabolic and radioactive calcium studies of the effects of hormones. Am J Med 37:269–293.PubMedCrossRefGoogle Scholar
  29. 29.
    Kaplan FS, Sawyer J, Connors S, et al. 1998 Urinary basic fibroblast growth factor: a biochemical marker for preosseous fibroproliferative lesions in patients with FOP. Clin Orthop Rel Res 346:59–65.Google Scholar
  30. 30.
    Kaplan FS, Smith RM. 1997 Fibrodysplasia ossificans progressiva (clinical vignette). J Bone Mineral Res 12:855.CrossRefGoogle Scholar
  31. 31.
    Kaplan FS, Tabas JA, Zasloff MA. 1990 Fibrodysplasia ossificans progressiva: A clue from the fly? Calcif Tiss Int 47:117–125.CrossRefGoogle Scholar
  32. 32.
    Shafritz AB, Shore EM, Gammon FH, et al. 1996 Overexpression of an osteogenic morphogen in fibrodysplasia ossificans progressiva. N Engl J Med 335:555–561.PubMedCrossRefGoogle Scholar
  33. 33.
    Kaplan FS, Ahn J, Serrano de la Peña L, Glaser DL, Shore EM. 2003 Fibrodysplasia ossificans progressiva (FOP): deciphering the molecular pathways of ectopic skeletogenesis. In: Rosier RN, Evans CH, eds. Molecular Biology in Orthopaedics. American Academy of Orthopaedic Surgeons, Rosemont, IL, pp. 95–105.Google Scholar
  34. 34.
    Kaplan FS, Glaser DL, Hebela N, Shore EM. 2004 Heterotopic ossification. J Am Acad Orthop Surg 12:116–125.PubMedGoogle Scholar
  35. 35.
    Serrano de la Peña L, Billings PC, Fiori JL, Ahn J, Kaplan FS, Shore EM. 2005 Fibrodysplasia ossificans progressiva (FOP), a disorder of ectopic osteogenesis misregulates cell surface expression and trafficking of BMPR1. J Bone Miner Res 20:1168–1176.CrossRefGoogle Scholar
  36. 36.
    Kussmaul, WG, Esmail AN, Sagar Y, Ross J, Gregory S, Kaplan FS. 1998 Pulmonary and cardiac function in advanced fibrodysplasia ossificans progressiva. Clin Orthop 346:104–109.PubMedGoogle Scholar

Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • Frederick S. Kaplan
    • 11
    • 1
    • 3
    Email author
  • David L. Glaser
    • 11
    • 3
  • Eileen M. Shore
    • 11
    • 1
    • 2
  • Gregory K. Deirmengian
    • 11
    • 3
  • Rishi Gupta
    • 11
    • 3
  • Patricia Delai
    • 4
  • Rolf Morhart
    • 5
  • Roger Smith
    • 6
  • Martine Le Merrer
    • 7
  • John G. Rogers
    • 8
  • J. Michael Connor
    • 9
  • Joseph A. Kitterman
    • 10
  1. 1.Department of MedicineThe University of Pennsylvania School of MedicinePhiladelphia
  2. 2.Department of GeneticsThe University of Pennsylvania School of MedicinePhiladelphia
  3. 3.The Center for Research in FOP and Related DisordersThe University of Pennsylvania School of MedicinePhiladelphia
  4. 4.The University of Santa Casa de Misericordia of São Paolo School of MedicineSão PaoloBrazil
  5. 5.KinderKlinik, Klinikum Garmisch-PanenKinchenGermany
  6. 6.Nuffield Orthopaedic CentreHeadingtonUK
  7. 7.Hôpital NeckerParisFrance
  8. 8.Royal Children's Hospital Genetics ClinicRoyal Children's HospitalMelbourneAustralia
  9. 9.Duncan Guthrie Institute of Medical GeneticsUniversity of Glasgow Medical SchoolGlasgowScotland
  10. 10.Department of Pediatrics and Cardiovascular Research InstituteUniversity of CaliforniaSan Francisco
  11. 11.Department of Orthopaedic SurgeryUniversity of Pennsylvania School of MedicinePhiladelphia

Personalised recommendations