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.
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 usually occurs before the age of 10. FOP is considered a genetic disease because 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. 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.
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 most well-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. Per his wishes, his preserved body now resides in the Mütter Museum and has proven to be an invaluable source of information in the study of FOP.
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. Activities that increase the risk of falling should be avoided, as injuries from falling can provoke the growth of bone.
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"). 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. ACVR1 encodes activin receptor type-1, a BMP type-1 receptor.