Fibrodysplasia ossificans progressiva (Fibrodysplasia ossificans progressive) - Gen ACVR1.
Fibrodysplasia ossificans progressiva (FOP) is a condition in which muscle tissue and connective tissue and tendons and ligaments gradually ossify, forming extra-skeletal or heterotopic bone limiting movement. In general, this process becomes noticeable in early childhood, starting with the neck and shoulders and down through the rest of the body and limbs.
The formation of extra-skeletal bone causes progressive loss of mobility as joints are affected. The inability to fully open the mouth can cause difficulty talking and eating. Eventually, people affected can become malnourished because their feeding problems and difficulties resulting from respiratory formation additional bone around the rib cage which restricts the expansion of the lungs. Any trauma to the muscles of an individual with fibrodysplasia ossificans progressiva, as a fall or invasive medical procedures, can trigger episodes of swelling and myositis, followed by a faster ossification in the injured area. People with the disease usually born with malformed thumbs. This anomaly of the fingers is a feature that helps distinguish this condition from other bone and muscle problems. Affected individuals may also have other short thumbs and skeletal abnormalities.
This process is due to mutations in the gene ACVR1, located on the long arm of chromosome 2 (2q23-q24). This gene encodes a member of a family of proteins called bone morphogenetic protein receptors (BMP) Type I protein is found in many body tissues, including skeletal muscle and cartilage. This protein helps control the growth and development of the bones and muscles, including the ossification occurs in normal skeletal development from birth to adulthood.
All individuals with a definite diagnosis of fibrodysplasia ossificans progressiva have a mutation in which the amino acid histidine is replaced by the amino acid arginine at position 206 of the protein (or Arg206His R206H). It is believed that, under certain conditions, this mutation may change the shape of the receiver under certain conditions and the mechanisms controlling alter receptor activity. As a result, the receptor may be constitutively active. Constitutive activation of the receptor causes the excessive growth of bone and cartilage and joint fusion, leading to the signs and symptoms of fibrodysplasia ossificans progressiva.
This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the alteration. Most fibrodysplasia ossificans progressiva cases are caused by new mutations in the gene and occur in people with no history of disease in your family. In a small number of cases, an affected person inherits the mutation from an affected parent.
Tests in IVAMI: in IVAMI perform detection of mutations associated with fibrodysplasia ossificans progressiva, by complete PCR amplification of exons ACVR1 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).