Al Mukaddam, Mona

Abstract Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic condition characterized by congenital malformations of the great toes and progressive heterotopic ossification (HO) in specific anatomic patterns. Present management summarized here is focused on early diagnosis, assiduous avoidance of injury and iatrogenic harm, symptomatic amelioration of painful flare-ups, and optimization of residual function. Twenty-one members of the International Clinical Council on FOP (ICC) and seven consultants from 15 countries, chosen for their clinical expertise in FOP, developed this summary statement. Further advances in therapeutics will be based on rigorous clinical trials to assess novel and emerging treatment and prevention strategies. A detailed and updated exploration of the topics outlined in this brief perspective can be found in “The Medical Management of Fibrodysplasia Ossificans Progressiva: Current Treatment Considerations” which can be found on the International Clinical Council on FOP (ICC) website (www.iccfop.org).

Abstract Pseudoarthroses (false joints) occur as a complication of fracture healing in the normotopic skeleton but have not been reported at ectopic sites. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by progressive heterotopic ossification (HO) and congenital skeletal abnormalities including developmental arthropathy in the normotopic skeleton. Here, we report ectopic pseudojoint formation in 6 patients with FOP, all occurring after painful flare-ups and HO in soft connective tissues of the knee, hip, and forearm. To our knowledge, FOP is the only human condition in which ectopic pseudojoint formation occurs. These findings support that dysregulated BMP pathway signaling from mutant ACVR1 mediates not only HO, but also ectopic pseudojoint formation, and that ectopic pseudojoints can arise from de novo musculoskeletal elements.