Fibrodysplasia ossificans progressiva (FOP) is a rare connective tissue disorder. FOP causes the soft tissue to transform permanently into bone in the muscles, tendons, ligaments, and other connective tissues. This heterotopic ossification (ossification in the wrong place) leads to greatly limited movement in the affected areas and sometimes the movement may be impossible. Heterotopic ossification becomes noticeable in early childhood, when the neck and shoulders are first affected. The process of heterotopic ossification continues to cover other parts of the body including, but not limited to, the neck, spine, chest elbows, hips, knee, and jaw. Therefore, the patient suffers from recurrent painful episodes of soft tissue swelling and the development of tumors in subcutis and muscle tissue. An injury to tissues must be avoided as it induces heterotopic ossification and further progression of the disease. People with FOP are generally born with malformed big toes, which is a distinguished feature of FOP and it is not found in other muscle and bone abnormalities. Affected individuals may also have short thumbs.
Fibrodysplasia ossificans progressiva (FOP) is an inherited autosomal dominant disorder, although many sporadic cases are caused by a high level of spontaneous mutations. The pattern of male-to-male transmission excludes X-linked inheritance. Mutations in the activin A receptor, type I (ACVR1) gene cause FOP. ACVR1 gene encodes for a protein family known as bone morphogenetic protein (BMP) type I receptors. BMP receptors play an important role in controlling bone and muscle growth. Alterations in ACVR1 gene will change the shape of BMP receptors and prevent their binding to other molecules. Therefore, the receptor's activity will be uncontrolled and may remain constantly active resulting in overgrowth of bone and cartilage and fusion of joint. In most cases, FOP results from new mutations. In addition, a new mutation of the noggin (NOG) gene has been identified in an FOP family.
