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Genetics Home Reference: your guide to understanding genetic conditions
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Fibrodysplasia ossificans progressiva

Reviewed August 2007

What is fibrodysplasia ossificans progressiva?

Fibrodysplasia ossificans progressiva (FOP) is a disorder in which muscle tissue and connective tissue such as tendons and ligaments are gradually replaced by bone (ossified), forming bone outside the skeleton (extra-skeletal or heterotopic bone) that constrains movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and proceeding down the body and into the limbs.

Extra-skeletal bone formation causes progressive loss of mobility as the joints become affected. Inability to fully open the mouth may cause difficulty in speaking and eating. Over time, people with this disorder may experience malnutrition due to their eating problems. They may also have breathing difficulties as a result of extra bone formation around the rib cage that restricts expansion of the lungs.

Any trauma to the muscles of an individual with fibrodysplasia ossificans progressiva, such as a fall or invasive medical procedures, may trigger episodes of muscle swelling and inflammation (myositis) followed by more rapid ossification in the injured area. Flare-ups may also be caused by viral illnesses such as influenza.

People with fibrodysplasia ossificans progressiva are generally born with malformed big toes. This abnormality of the big toes is a characteristic feature that helps to distinguish this disorder from other bone and muscle problems. Affected individuals may also have short thumbs and other skeletal abnormalities.

How common is fibrodysplasia ossificans progressiva?

Fibrodysplasia ossificans progressiva is a very rare disorder, believed to occur in approximately 1 in 2 million people worldwide. Several hundred cases have been reported.

What genes are related to fibrodysplasia ossificans progressiva?

Mutations in the ACVR1 gene cause fibrodysplasia ossificans progressiva.

The ACVR1 gene provides instructions for producing a member of a protein family called bone morphogenetic protein (BMP) type I receptors. The ACVR1 protein is found in many tissues of the body including skeletal muscle and cartilage. It helps to control the growth and development of the bones and muscles, including the gradual replacement of cartilage by bone (ossification) that occurs in normal skeletal maturation from birth to young adulthood.

Researchers believe that a mutation in the ACVR1 gene may change the shape of the receptor under certain conditions and disrupt mechanisms that control the receptor's activity. As a result, the receptor may be constantly turned on (constitutive activation). Constitutive activation of the receptor causes overgrowth of bone and cartilage and fusion of joints, resulting in the signs and symptoms of fibrodysplasia ossificans progressiva.

Related Gene(s)

Changes in this gene are associated with fibrodysplasia ossificans progressiva.

  • ACVR1

How do people inherit fibrodysplasia ossificans progressiva?

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Most cases of fibrodysplasia ossificans progressiva result from new mutations in the gene. These cases occur in people with no history of the disorder in their family. In a small number of cases, an affected person has inherited the mutation from one affected parent.

Where can I find information about diagnosis or management of fibrodysplasia ossificans progressiva?

These resources address the diagnosis or management of fibrodysplasia ossificans progressiva and may include treatment providers.

  • Genetic Testing Registry: Progressive myositis ossificans (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0016037)

You might also find information on the diagnosis or management of fibrodysplasia ossificans progressiva in Educational resources (http://www.ghr.nlm.nih.gov/condition/fibrodysplasia-ossificans-progressiva/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/fibrodysplasia-ossificans-progressiva/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about fibrodysplasia ossificans progressiva?

You may find the following resources about fibrodysplasia ossificans progressiva helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for fibrodysplasia ossificans progressiva?

  • Myositis Ossificans
  • Myositis ossificans progressiva
  • Progressive myositis ossificans
  • progressive ossifying myositis

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about fibrodysplasia ossificans progressiva?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding fibrodysplasia ossificans progressiva?

ankylosis ; autosomal ; autosomal dominant ; bone formation ; cartilage ; cell ; connective tissue ; constitutive ; gene ; inflammation ; inherited ; mutation ; ossification ; protein ; receptor ; skeletal muscle ; tissue ; trauma

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Ahn J, Serrano de la Pena L, Shore EM, Kaplan FS. Paresis of a bone morphogenetic protein-antagonist response in a genetic disorder of heterotopic skeletogenesis. J Bone Joint Surg Am. 2003 Apr;85-A(4):667-74. (http://www.ncbi.nlm.nih.gov/pubmed/12672843?dopt=Abstract)
  • Blaszczyk M, Majewski S, Brzezinska-Wcislo L, Jablonska S. Fibrodysplasia ossificans progressiva. Eur J Dermatol. 2003 May-Jun;13(3):234-7. (http://www.ncbi.nlm.nih.gov/pubmed/12804980?dopt=Abstract)
  • OMIM: FIBRODYSPLASIA OSSIFICANS PROGRESSIVA (http://omim.org/entry/135100)
  • Fiori JL, Billings PC, de la Peña LS, Kaplan FS, Shore EM. Dysregulation of the BMP-p38 MAPK signaling pathway in cells from patients with fibrodysplasia ossificans progressiva (FOP). J Bone Miner Res. 2006 Jun;21(6):902-9. (http://www.ncbi.nlm.nih.gov/pubmed/16753021?dopt=Abstract)
  • Gannon FH, Glaser D, Caron R, Thompson LD, Shore EM, Kaplan FS. Mast cell involvement in fibrodysplasia ossificans progressiva. Hum Pathol. 2001 Aug;32(8):842-8. (http://www.ncbi.nlm.nih.gov/pubmed/11521229?dopt=Abstract)
  • Groppe JC, Shore EM, Kaplan FS. Functional modeling of the ACVR1 (R206H) mutation in FOP. Clin Orthop Relat Res. 2007 Sep;462:87-92. (http://www.ncbi.nlm.nih.gov/pubmed/17572636?dopt=Abstract)
  • Kaplan FS, Glaser DL, Pignolo RJ, Shore EM. A new era for fibrodysplasia ossificans progressiva: a druggable target for the second skeleton. Expert Opin Biol Ther. 2007 May;7(5):705-12. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17477807?dopt=Abstract)
  • Nakajima M, Haga N, Takikawa K, Manabe N, Nishimura G, Ikegawa S. The ACVR1 617G>A mutation is also recurrent in three Japanese patients with fibrodysplasia ossificans progressiva. J Hum Genet. 2007;52(5):473-5. Epub 2007 Mar 10. (http://www.ncbi.nlm.nih.gov/pubmed/17351709?dopt=Abstract)
  • O'Connell MP, Billings PC, Fiori JL, Deirmengian G, Roach HI, Shore EM, Kaplan FS. HSPG modulation of BMP signaling in fibrodysplasia ossificans progressiva cells. J Cell Biochem. 2007 Dec 15;102(6):1493-503. (http://www.ncbi.nlm.nih.gov/pubmed/17516498?dopt=Abstract)
  • Olmsted EA, Kaplan FS, Shore EM. Bone morphogenetic protein-4 regulation in fibrodysplasia ossificans progressiva. Clin Orthop Relat Res. 2003 Mar;(408):331-43. (http://www.ncbi.nlm.nih.gov/pubmed/12616078?dopt=Abstract)
  • Scarlett RF, Rocke DM, Kantanie S, Patel JB, Shore EM, Kaplan FS. Influenza-like viral illnesses and flare-ups of fibrodysplasia ossificans progressiva. Clin Orthop Relat Res. 2004 Jun;(423):275-9. (http://www.ncbi.nlm.nih.gov/pubmed/15232462?dopt=Abstract)
  • Shore EM, Xu M, Feldman GJ, Fenstermacher DA, Cho TJ, Choi IH, Connor JM, Delai P, Glaser DL, LeMerrer M, Morhart R, Rogers JG, Smith R, Triffitt JT, Urtizberea JA, Zasloff M, Brown MA, Kaplan FS. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. 2006 May;38(5):525-7. Epub 2006 Apr 23. Erratum in: Nat Genet. 2007 Feb;39(2):276. FOP International Research Consortium [removed]; Cho, Tae-Joon [added]; Choi, In Ho [added]; Connor, J Michael [added]; Delai, Patricia [added]; Glaser, David L [added]; LeMerrer, Martine [added]; Morhart, Rolf [added]; Rogers, John G [added]; Smith, Roger [added]; Triffitt, James T [added]; Urtizberea, J Andoni [added]; Zasloff, Michael [added]. (http://www.ncbi.nlm.nih.gov/pubmed/16642017?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: August 2007
Published: August 25, 2014