The Curious Case Files: Fibrodysplasia Ossificans Progressiva (FOP)

Med Connection

Dear Prospective Medical Students, it's time to scrub in.

Let us dissect the incredibly rare and intriguing case that is Fibrodysplasia Ossificans Progressiva.

Overview & Cause

FOP is an extremely rare, autosomal dominant, genetic disorder estimated to affect only 1 out of 2 million people worldwide. Tendons, muscles, and connective tissue eventually metamorphose into bone, forming a second skeleton (NORD). The disorder restricts movement due to the bone taking the place of soft tissue and will progressively worsen, possibly even leading to total immobility.

The disease is caused by a mutation in the ACVR1 gene. This gene, when healthy, ‘provides instructions for making the activin receptor type-1 (ACVR1) protein, which is a member of a protein family called bone morphogenetic protein (BMP) type I receptors’ (Medline). The BMP pathway regulates osteoblast (bone-forming) activity. When the BMPs bind to ACVR1 receptors, it trigger new bone formation and regulate the metamorphosis of existing cartilage into bone. In normal cells, the ACVR1 is activated in the development of children, where bone must grow or when there is physical trauma that requires bone repair. In FOP, this receptor is overactive, and cells receive constant signals for stem cells to form osteoblasts, therefore forming new bone. Minor injuries can trigger bone formation, causing the disorder to progress, eventually leading to complete immobility where the body’s tissues and ligaments have been overtaken by bones.

Symptoms

Diagnosis

Management & Treatment