Fibrodysplasia ossificans progressiva

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Overview
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.

Symptoms
Children born with FOP characteristically have short big toes. 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 overnight. 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. 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 periodic references in medical literature describing people who apparently "turned to stone", and it is possible that some of these cases may have been attributable to FOP.

Perhaps the most well-known FOP case is that of Harry Eastlack. His condition began to develop around the age of ten, and by the time of his death from pneumonia in November 1973 (six days before his fortieth birthday), his body had completely ossified, leaving him able to move only his lips.

What makes Eastlack’s case particularly 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 skeleton now resides in The Mütter Museum (see a QuickTime animation) in the College of Physicians of Philadelphia, and has proven to be an invaluable source of information in the study of FOP.

Treatment
There is no known cure for FOP. Those diagnosed with FOP should try to avoid falling or getting bruises, and avoid intramuscular injections since these can cause bone to grow. Likewise, people with FOP should never stretch their joints outside of their normal range of motion. However since flare-ups can occur spontaneously, even perfect preventive care cannot guarantee the absence of bone growths.

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. About 2,500 cases have been reported to date, but a study has determined that it affects approximately 1 in 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 I receptor.

Fibrodysplasia ossificans progressiva in popular culture
The subject of Fibrodysplasia ossificans is discussed in a Dinosaur Comic.

A patient on Grey's Anatomy (Season 3, episode 19: "Grey's Anatomy episodes (Season 3) My Favorite Mistake") had this disease. She was reduced to the use of only her hands and face. They were unable to perform heart surgery when it was needed because of the disease.