Recent advances in Fibrodysplasia Ossificans Progressiva (FOP)

Number 146
Date 7 November 2006

A workshop on fibrodysplasia ossificans progressiva (FOP) was held for the third time, after an interval of seven years, to discuss the recent exciting advances in FOP research and clinical treatment. Participants included thirteen clinicians and scientists from six countries. FOP is a rare genetic disorder of skeletal malformations and progressive heterotopic ossification that replaces many skeletal muscles with a second skeleton.  FOP is a most distressing genetic disorder that inevitably leads to complete immobility in later life.  Although FOP is a rare condition, genetic, cellular and molecular insights into FOP will lead to increased knowledge of more common disorders that affect muscle and bone formation, such as heterotopic ossification following spinal cord injury, head injury, athletic injuries, and hip replacement surgery.

The meeting opened with each participant identifying their expertise and the resources available to the groups. The major clinical features of FOP were defined and cases of atypical phenotypes described. Recent insights into the cell signalling pathways involved in bone formation as well as the identification of five critical multigenerational FOP families have led to the identification of the mutation causing FOP. Genetic mutations were identified and correlated with severity of clinical phenotype. The causative gene is an overactive cell surface receptor – essentially a cellular switch that triggers the replacement of muscle by bone. Important new research directions were formulated and include investigating the mechanisms by which the switch is activated and the subsequent downstream signalling events, together with the development of relevant animal models to study the biology. A significant focus of future studies will be on therapeutic treatment possibilities for this catastrophically disabling disorder. These aspects, together with recommended current treatment options for FOP patients and counselling for patients and families, were extensively discussed by the workshop participants. The group aims to keep in close contact and reconvene at an appropriate time within the next couple of years when further extensive progress on knowledge of the condition is highly likely.

Workshop Convenors: James T Triffitt and Frederick S. Kaplan

Workshop Participants: D. Antisevic, S. Brown, J.M. Connor, D. Graf, M. le Merrer, C. Netelenbos, K. Petrie, R.J. Pignolo, H.I. Roach, E.M. Shore, R. Smith