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1st Source
Fibrodysplasia ossificans progressiva (FOP), sometimes referred to as Stone Man Syndrome, 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.
Symptoms
Children born with FOP 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. Specifically, FOP involvement is typically seen first in the dorsal, axial, cranial and proximal regions of the body. Later the disease progresses in the in the ventral, appendicular, caudal and distal regions of the body. However it does not necessarily occur in this order due to injurycaused 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. The bone that results occurs independently of the normal skeleton, forming its own discrete skeletal elements. These elements, however, can fuse with normal skeletal bone. Interestingly, the diaphragm, tongue, and extra-ocular muscles are spared in this process, as well as cardiac and smooth muscle. 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 or fibrosis. 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"; some of these cases may be attributable to FOP.
The best known FOP case is that of Harry Eastlack (19331973). 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 Mtter Museum in Philadelphia, and has proven to be an invaluable source of information in the study of FOP. Currently, there are approximately 450 confirmed cases of FOP in the world.
Treatment
There is no known cure for FOP. Attempts to surgically remove the bone result in more robust bone growth. While under anesthesia, patients with FOP may face problems, which include difficulties with intubation, restrictive pulmonary disease and changes in the electrical conduction system of the heart. Activities that increase the risk of falling should be avoided, as injuries from falling can provoke the growth of bone. In 1999 scientists discovered that squalamine in sharks 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. A trial of squalamine started in 2002 but terminated about 2007. (Note that squalene is a different compound, also found in sharks, that has no such properties.) As of November 2010 there are no registered clinical trials for FOP.
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) 10-6 mutations per gene per generation"). A similar but less catastrophic disease is fibrous dysplasia, which is caused by a post-zygotic mutation. A mutation in the gene ACVR1 (= ALK2) is responsible for the disease. 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. This causes endothelial cells to transform to mesenchymal stem cells and then to bone.
2nd Source
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.
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.
Myositis Ossificans Myositis ossificans progressiva Progressive myositis ossificans progressive ossifying myositis
3rd Source
Fibrodysplasia ossificans progressiva (FOP) is a rare genetic disorder that causes soft tissues to transform permanently into bone. These bones grow abnormally in the muscles, tendons, ligaments and other connective tissues, forming bridges of extra bone across the joints. As a result, movement in the areas affected by FOP is greatly restricted and sometimes impossible. The condition affects many areas of the body including, but not limited to, the neck, spine, chest, shoulders, elbows, wrists, hips, knees, ankles and jaw. FOP is an autosomal dominant condition, which means that a person needs only to get the gene for FOP from one parent to inherit the disease. In most cases, however, FOP is a new mutation or an accident of nature. In fact, the parents of FOP patients typically don't have the disease. A person with FOP, however, has a 50 percent chance of passing it on to his or her child.
experiences some sort of trauma to the body, such as a bump or fall. Episodes also can occur without any warning or may not occur at all. In most cases, the nodules transform into bone during a process known as heterotopic ossification. When the body starts to generate new bone, the patient usually experiences a painful flare-up. Tissue swelling, joint stiffness and serious discomfort can occur. Some may have a low-grade fever. Flare-ups can last as long as six to eight weeks. The disease then progresses along the trunk and limbs of the body. These lesions slowly replace the body's muscles with normallooking bone.
Diagnose
In most cases, an accurate diagnosis of fibrodysplasia ossificans progressiva (FOP) can be made based on a patient's characteristic malformation of the big toe, in addition to rapidly changing swellings on the head, neck or back. Due to a lack of knowledge of FOP among doctors, the rate of misdiagnosis of the disease is estimated at 80 percent or higher. These errors in diagnosing FOP have caused pain and suffering for FOP patients and their families worldwide. For instance, misdiagnosis has led to unnecessary invasive procedures, such as biopsies, as well as permanent complications from medical interventions, including loss of mobility. Three of the most common misdiagnoses for FOP are cancer, aggressive juvenile fibromatosis, also called desmoid tumors, and progressive osseous heteroplasia, another rare disease characterized by the abnormal growth of bone.
Treatment
Unfortunately, there is no effective treatment for fibrodysplasia ossificans progressiva (FOP). Surgery is not an option for removing the excess bones because surgery often results in more bone formation. And these new bones don't disappear on their own. The good news is that researchers are investigating FOP and new treatments. For example, a drug is being developed that may help to control bone growth. Medications also are available to help relieve symptoms of FOP, such as pain and inflammation. Since FOP is a progressive disease, it typically gets worse over time as the patient ages, but the rate of new bone formation differs for each person and the disease's progression is generally unpredictable. Although a person is born with FOP, extra bone may not appear at birth and he or she may go months or years without experiencing a flare-up, which signals the development of new bone.