eMedicine Specialties > Dermatology > Pediatric Diseases

Fibrodysplasia Ossificans

Author: Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Coauthor(s): Slawomir Majewski, MD, Professor and Director, Department of Dermatology and Venereology, Warsaw School of Medicine, Poland; Sebastian S Majewski, MD, Consulting Staff, Department of Dermatology, Military Institute of Health Services, Warsaw, Poland; Stefania Jablonska, MD, Chairman, Professor Emeritus, Department of Dermatology, Warsaw School of Medicine, Poland
Contributor Information and Disclosures

Updated: May 12, 2008

Introduction

Background

Fibrodysplasia ossificans progressiva (FOP) is a rare, severely disabling, autosomal dominant disease characterized by recurrent painful episodes of soft tissue swelling and the development of tumors in subcutis and muscle tissue. These lesions lead to heterotopic ossification, that is, true bone tissue formation in the axial musculature, the ligaments, the fascia, the aponeurosis, the tendons, and the joint capsules. A variety of congenital skeletal malformations of the hands and the feet, especially a hallus valgus deformity with microdactyly, also are characteristic.

The eMedicine articles Myositis Ossificans and Heterotopic Ossification may be helpful.

Pathophysiology

The pathophysiology of FOP is unknown. It is an inherited autosomal dominant disorder with complete penetration but variable gene expressivity. Recent findings suggest that FOP maps to band 4q27-31, a region that contains at least 1 gene involved in the bone morphogenic protein (BMP) signaling pathway. BMPs are members of the transforming growth factor-beta superfamily and play a role in the development of bone and other tissues. The condition is multifocal, starting to develop usually after traumatization.

A number of mutations have been documented. A mutation of the noggin (NOG) gene in an FOP family has been described.1 The FOP gene in the 17q21-22 region had been observed with several mutations described in the NOG gene (located in 17q22) in 4 FOP patients, including the G91C mutation, which was transmitted dominantly in a Spanish FOP family. This mutation is a guanine to adenine change at nucleotide 283 (283G–>A) of the NOG gene and was transmitted by the affected mother to her 2 affected children. A novel mutation in the activin A type 1 receptor gene was described in one patient. Analysis showed that the patient was heterozygous for a mutation, G356D.2 A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic FOP.3 In this study, FOP was mapped to 2q23-24 by linkage analysis.

Frequency

International

The prevalence has been estimated at 1 case per 1.64 million persons in the United Kingdom. Fewer than 200 cases have been described worldwide.

Mortality/Morbidity

FOP usually starts in early infancy, although skeletal deformations are present at birth. The prognosis is poor because of the involvement of thoracic muscles, leading to restrictive lung disease.

Race

The disease mainly occurs in whites, but it is also reported in blacks.

Sex

FOP is more common in females than in males. The observed male-to-male transmission of the disorder excludes X-linked inheritance. Because few individuals who are affected choose to have children, most patients are considered to have new mutations.

Age

FOP usually starts in early infancy; however, reports exist of in utero involvement and skeletal deformations are present at birth.

Clinical

History

  • In most cases, FOP starts in early infancy with episodes of soft tissue swelling; however, reports exist of in utero involvement.
  • Ectopic bone formation is usually first evident in early childhood in children aged 2-6 years.
    • The main target is the axial musculature, but eventually ectopic bone formation occurs in the ligaments, the fascia, the aponeuroses, the tendons, and the joint capsules.
    • Involvement often demonstrates a proximal-to-distal predilection.
  • Most patients become bedridden by time they are in their 30s.

Physical

  • Lesions are characterized by painful, tender, rubbery, soft tissue indurations, usually precipitated by a trauma.
  • Lesions mainly develop in the paraspinal muscles of the back and in the limb girdles.
  • Some of the tumors undergo ossification, which can also affect the tendons, the ligaments, and the fascia.
  • Characteristics of diagnostic value are a hallus valgus deformity (present at birth), torticollis (due to involvement of the sternocleidomastoid muscle), joint immobilization (due to periarticular ossificans), and a thorax deformity (both lateral and anteroposterior).
  • Proximal tibial osteochondromas are a common phenotypic feature.4
  • Mobility is restricted because of ankylosis of the spine and the rib cage.
  • FOP is sometimes associated with alopecia and deafness.

Causes

FOP is an idiopathic condition precipitated by trauma.

More on Fibrodysplasia Ossificans

Overview: Fibrodysplasia Ossificans
Differential Diagnoses & Workup: Fibrodysplasia Ossificans
Treatment & Medication: Fibrodysplasia Ossificans
Follow-up: Fibrodysplasia Ossificans
Multimedia: Fibrodysplasia Ossificans
References
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References

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  2. Furuya H, Ikezoe K, Wang L, Ohyagi Y, Motomura K, Fujii N, et al. A unique case of fibrodysplasia ossificans progressiva with an ACVR1 mutation, G356D, other than the common mutation (R206H). Am J Med Genet A. Feb 15 2008;146(4):459-63. [Medline].

  3. Shore EM, Glaser DL, Gannon FH. Osteogenic induction in hereditary disorders of heterotopic ossification. Clin Orthop Relat Res. May 2000;(374):303-16. [Medline].

  4. Deirmengian GK, Hebela NM, O'Connell M, Glaser DL, Shore EM, Kaplan FS. Proximal tibial osteochondromas in patients with fibrodysplasia ossificans progressiva. J Bone Joint Surg Am. Feb 2008;90(2):366-74. [Medline].

  5. Dzukou T, Barbier C, Spyckerelle C, Labarrière F, Vittu G, Kremp O. [Fibrodysplasia ossificans progressiva in children. The interest of early diagnosis and treatment]. Presse Med. Mar 12 2005;34(5):373-7. [Medline].

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  15. Feldman G, Li M, Martin S, Urbanek M, Urtizberea JA, Fardeau M, et al. Fibrodysplasia ossificans progressiva, a heritable disorder of severe heterotopic ossification, maps to human chromosome 4q27-31. Am J Hum Genet. Jan 2000;66(1):128-35. [Medline].

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  28. Smith R. 61st ENMC-sponsored international workshop: Fibrodysplasia (myositis) ossificans progressiva (FOP), 10-12th July 1998, Naarden, The Netherlands. Neuromuscul Disord. Oct 1999;9(6-7):434-5. [Medline].

  29. Sy MH, Diouf A, Diallo BK, Dansokho AV, Ndiaye A, Tall A, et al. [Fibrodysplasia ossificans progressiva or Munchmeyer disease apropos of 2 cases]. Dakar Med. 1999;44(1):126-30. [Medline].

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Further Reading

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Keywords

fibrodysplasia ossificans progressive, FOP, myositis ossificans progressiva, myositis ossificans

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Contributor Information and Disclosures

Author

Robert A Schwartz, MD, MPH, Professor and Head of Dermatology, Professor of Medicine, Professor of Pediatrics, Professor of Pathology, Professor of Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Slawomir Majewski, MD, Professor and Director, Department of Dermatology and Venereology, Warsaw School of Medicine, Poland
Disclosure: Nothing to disclose.

Sebastian S Majewski, MD, Consulting Staff, Department of Dermatology, Military Institute of Health Services, Warsaw, Poland
Disclosure: Nothing to disclose.

Stefania Jablonska, MD, Chairman, Professor Emeritus, Department of Dermatology, Warsaw School of Medicine, Poland
Disclosure: Nothing to disclose.

Medical Editor

Jean Paul Ortonne, MD, Chair, Department of Dermatology, Professor, Hospital L'Archet, Nice University, France
Jean Paul Ortonne, MD is a member of the following medical societies: American Academy of Dermatology and American Dermatological Association
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Director, Division of Dermatology, Scott and White Clinic; Director Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: 3M Pharmaceutical Grant/research funds Other; Graceway Pharmaceuticals Grant/research funds Other

Managing Editor

Jeffrey J Miller, MD, Associate Professor, Department of Dermatology, Penn State University, Milton S Hershey Medical Center
Disclosure: Nothing to disclose.

CME Editor

Catherine Quirk, MD, Clinical Assistant Professor, Department of Dermatology, Brown University
Catherine Quirk, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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