Ectopic pseudojoints in fibrodysplasia ossificans progressiva

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.