Fibrodysplasia Ossificans Progressiva

Excerpt

Fibrodysplasia ossificans progressiva is described as a rare genetic disorder characterized by the organization of heterotopic hard tissues within the soft tissues, such as ligaments, tendons, and skeletal muscle. It comes under the category of an autosomal dominant disorder. The tissue formed in such patients is not just the mineralized calcium phosphate, but it resembles the new bone formation by osteoblast cells via endochondral ossification. Most of the patients who are suffering from Fibrodysplasia ossificans progressiva can move their joints normally at the time of birth, but disability arises in various joints when they reach their 30’s because gradually hetero­topic bones fuse and result in bridge formation with normal bones. Injury to soft tissues can lead to acute heterotopic bone formation in such patients hence invasive procedures, such as injection, surgical operation, and biopsy, are contraindicated.

Making a diagnosis of fibrodysplasia ossificans progressiva was difficult for a long time as there were no reliable biomarkers for such cases that could be evaluated in urine or peripheral blood. The pathogenesis found in such patients is the gain of function mutation in the ACVR1/ALK2 gene located over chromosome 2 and the involvement of the bone morphogenetic proteins (BMP) signaling pathway. The BMPs lead to the formation of heterotopic bone in the soft tissues. The most common sites affected are the shoulders, neck, and spine. The median age of survival is roughly around 40 years. Death occurs in such cases primarily due to thoracic insufficiency syndrome and related complications. PCR is the main diagnostic modality for the analysis of genetic mutation in FOP.