A rare genetic connective tissue disorder characterized by a short toe, fibrous dysplasia and bone formation in muscles, ligaments, tendons and soft connective tissue.
Fibrodysplasia ossificans progressiva
Genetics of Fibrodysplasia Ossificans Progressiva: FOP is an autosomal dominant condition, but most cases are sporadic. FOP patients have a genetic fault, which means that their bodies cannot switch off the mechanism that grows the skeleton in the womb. Any small injury to connective tissue (muscles, ligaments, and tendons) can result in the formation of hard bone around the damaged site. Children are born with a characteristic malformation of the great toes and begin to develop heterotopic (extra) bone formation during early childhood. Eventually, a second skeleton begins to form that severely restricts mobility.
Because of the very small numbers of patients, identifying the mutation(s) causing FOP is difficult. There are several genes that have been implicated in the disease process. For example, when the Noggin gene (NOG) is deleted in mice, the mice are unable to stop the deposition of bone, causing an FOP-like disease. Another gene of interest is the Bone Morphogenic Protein gene (BMP), which Noggin regulates. Proteins encoded by BMP induce bone formation, and one of their roles is to stimulate the formation of the fetal skeleton. In FOP, lymphocytes deliver BMP4 to areas of damaged muscle, and so initiate bone growth rather than aid tissue repair. (Source: Genes and Disease by the National Center for Biotechnology )