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. The growths cannot be removed with surgery because such removal causes the body to "repair" the area of surgery with more bone.^[1]

Symptoms

Children born with FOP characteristically have deformed big 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 is usually before the age of 10. It is considered a genetic disease because the bone growth starts from the top down just as bones grow on fetuses. For example, a child with FOP will develop bones starting on the neck, then shoulders, arms, chest area and finally on the feet. Often, the tumor-like lumps that characterize the disease appear suddenly. The gene causing the ossification is normally deactivated when the child's bones are made in the womb, but in patients with FOP, this 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.

Cases

Since the 1800s there have been references in medicine describing people who apparently "turned to stone" and it is possible that some of these cases may have been attributable to FOP.

The most well-known FOP case is 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.

What makes Eastlack's case notable is that shortly before his 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. As per his wishes, his preserved body now resides in the Mutter Museum and has proven to be an invaluable source of information in the study of FOP.

Treatment

There is no known cure for FOP. However, scientists have discovered a gene in sharks that may hold the cure for those suffering from FOP.^[3] Activities that increase the risk of falling should be avoided, as injuries from falling can provoke the growth of bone. ^[4]

Causes

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) x 10(-6) mutations per gene per generation").^[5] 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.^[6] ACVR1 encodes activin receptor type-1, a BMP type-1 receptor.

Sources

• The International FOP Association

References

1. ↑
2. ↑
3. ↑ BBC News, "Shark therapy for bizarre bone disease," March 24, 1999
4. ↑ The New York Times, "Finally, With Genetic Discovery, Hope for Escape From a Prison of Bone", May 9, 2006
5. ↑
6. ↑

External links

• The Girl Whose Muscles are Turning to Bone

de:Fibrodysplasia ossificans progressiva es:Fibrodisplasia osificante progresiva eo:Progresa osti?a fibrodisplazio fr:Fibrodysplasie ossifiante progressive nl:Progressieve myositis ossificans ja:???????????? pl:Post?puj?ce kostniej?ce zapalenie mi??ni pt:Fibrodisplasia ossificante progressiva