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Fibrodysplasia ossificans progressiva
Classification and external resources
ICD-10 M61.1
ICD-9 728.11
OMIM 135100
eMedicine derm/609
MeSH D009221

Fibrodysplasia ossificans progressiva (FOP) is an extremely rare disease of the connective tissue. A mutation of the body's repair mechanism causes fibrous tissue (including muscle, tendon, and ligament) to be ossified when damaged. In many cases, injuries can cause joints to become permanently frozen in place. Surgical removal of the extra bone growths has been shown to cause the body to "repair" the affected area with more bone.[1]



Children born with FOP characteristically have deformed great toes, possibly missing a joint or simply presenting with a notable lump at the minor joint. The first "flare-up" that leads to the formation of FOP bones usually occurs before the age of 10. FOP is a genetic disease. The bone growth progresses from the top downward, just as bones grow in fetuses. A child with FOP will typically develop bones starting at the neck, then on the shoulders, arms, chest area and finally on the feet. However it does not necessarily occur in this order due to injury-caused flare-ups. Often, the tumor-like lumps that characterize the disease appear suddenly. The gene that causes ossification is normally deactivated after a fetus' bones are formed in the womb, but in patients with FOP, the gene keeps working. Aberrant bone formation in patients with FOP occurs when injured connective tissue or muscle cells at the sites of injury or growth incorrectly express an enzyme for bone repair during apoptosis (self-regulated cell death), resulting in lymphocytes containing excess bone morphogenetic protein 4 (BMP4) provided during the immune system response. Since the incorrect enzyme remains unresolved within the immune response, the body continues providing the incorrect BMP4-containing lymphocytes. BMP4 is a product that contributes to the development of the skeleton in the normal embryo.[2]

Because the disease is so rare, the symptoms are often misdiagnosed as cancer. This leads doctors to order biopsies, which can actually exacerbate the growth of these lumps.


Since the 1800s there have been references in medicine describing people who apparently "turned to stone"; some of these cases may be attributable to FOP.

The best known FOP case is that of Harry Eastlack (1933–1973). His condition began to develop at the age of ten and, by the time of his death from pneumonia in November 1973, six days before his 40th birthday, his body had completely ossified, leaving him able to move only his lips.

Shortly before Eastlack's death he made it known that he wanted to donate his body to science, in the hope that in death he would be able to help find a cure for this little-understood and particularly cruel disease. Pursuant to his wishes, his preserved skeleton is now kept at the Mütter Museum in Philadelphia, and has proven to be an invaluable source of information in the study of FOP.


There is no known cure or treatment for fibrodysplasia ossificans progressiva.

Activities that increase the risk of falling should be avoided, as injuries from falling can provoke the growth of bone.[3]

In 1999 scientists discovered that squalamine in sharks[4] might be useful in treating those suffering from FOP. Squalamine is antiangiogenic and can prevent the growth of blood vessels in cartilaginous tissue, thus preventing creation of bone in sharks.[5]. A trial of squalamine started in 2002[6]. Note that squalene is a different compound, also found in sharks, that has no such properties.


FOP is caused by an autosomal dominant allele on chromosome 2q23-24. The allele has variable expressivity, but complete penetrance. Most cases are caused by spontaneous mutation in the gametes; most people with FOP cannot have children. A study has determined that it affects approximately 1 in every 2 million people ("1.8 (SE ± 1.04) × 10-6 mutations per gene per generation").[7] A similar but less catastrophic disease is fibrous dysplasia, which is caused by a post-zygotic mutation.

Researchers from the University of Pennsylvania announced in April 2006 that a mutation in the gene ACVR1 is responsible for the disease.[8] ACVR1 encodes activin receptor type-1, a BMP type-1 receptor. The mutation causes the ACVR1 protein to have the amino acid histidine substituted for the amino acid arginine at position 206.[9]



  1. ^ "ABC News: When Body Turns to Bone". Retrieved 2007-06-02. 
  2. ^ Kierszenbaum, Abraham (2002). Histology and cell biology. New York: Mosby. ISBN 9780323016391. 
  3. ^ The New York Times, "Finally, With Genetic Discovery, Hope for Escape From a Prison of Bone", May 9, 2006
  4. ^ [1]
  5. ^ BBC News, "Shark therapy for bizarre bone disease," March 24, 1999
  6. ^ [2]
  7. ^ Connor JM, Evans DA (1982). "Genetic aspects of fibrodysplasia ossificans progressiva" (abstract). J. Med. Genet. 19 (1): 35–9. doi:10.1136/jmg.19.1.35. PMID 7069743. 
  8. ^ Shore EM, Xu M, Feldman GJ, et al. (2006). "A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva" (abstract). Nat. Genet. 38 (5): 525–7. doi:10.1038/ng1783. PMID 16642017. 
  9. ^ News Release of FOP's Cause

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