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Fibrodysplasia ossificans progressiva (FOP) is an extremely rare autosomal dominant form of connective tissue disorder characterized by congenital malformation of the great toes and progressive, disabling heterotopic osteogenesis in predictable anatomical patterns. Heterotopic bone formations lead to a debilitating, progressive ankylosis of the trunk, limbs and jaw. The mechanism by which bone forms out of muscles, tendons and ligaments is still poorly understood, but bone morphogenetic proteins (BMP), and particularly BMP4, are likely to play a direct or indirect role. The unraveling of the genetic defect is still hampered by the paucity of multigenerational families. Linkage studies suggest the FOP locus maps to chrosomome 4. A putative genetic heterogeneity, once hypothesized, has not been confirmed. Genetic counseling for FOP is difficult because of the absence of specific biological markers or reliable linkage studies. The risk of having a second affected child is nevertheless limited in a given family with a sporadic case. Therapeutic measures are essentially preventive and aimed at reducing the impact of trauma and falls and iatrogenic complications. |