Fibrodysplasia ossificans progressiva (FOP)

Fibrodysplasia ossificans progressiva (FOP) is a rare genetic musculoskeletal condition that causes bone to form outside the skeleton (ossification). This extra bone locks the joints, progressively limiting movement and creating a second skeleton that traps the body in bone. 

Doctors who diagnose and treat FOP include orthopaedists, rheumatologists, endocrinologists, and neurologists. Penn Medicine researchers were the first to identify the gene mutation responsible for FOP. We continue to focus on developing our understanding of this condition to help uncover effective therapies.

Symptoms of FOP typically appear in early childhood. Almost all people with FOP are born with deformities in both big toes, which can be mistaken for bunions. Symptoms typically start in the neck and shoulders before spreading to other areas of the body. Unpredictable episodes, or flare-ups, of soft-tissue swelling, pain, stiffness, and reduced movement can occur.

Other symptoms include:

• Abnormal bone formation in muscles, ligaments, and connective tissues
• Limited mobility due to stiff or locked joints
• Difficulty eating or speaking caused by restricted mouth movement from irregular bone growth
• Hearing loss if FOP affects the small bones in the middle ear (ossicles)
• Breathing difficulties as extra bone growth around the rib cage limits lung expansion
• Painful, red or purple, tumor-like swellings that feel warm to the touch
• Spine deformities like scoliosis or kyphosis
• Swelling in the neck, shoulders, and back
• Permanent loss of movement

Most cases of FOP result from a mutation in the ACVR1/ALK2 gene, which regulates a protein responsible for bone growth. In people with FOP, this mutation disrupts the bone morphogenetic protein (BMP) signal, keeping it active when it should be off. This abnormal signaling can trigger bone formation in response to injuries or inflammation. Even routine procedures, such as intramuscular injections, vaccinations, or blood draws, may lead to abnormal bone growth. 

In most cases, the gene mutation occurs in people with no family history of the disorder. Inherited cases, where the mutation is passed from an affected parent, are rare. 

Penn Medicine researchers discovered the gene mutation that causes FOP, unlocking a deeper understanding of how the condition affects tissues and paving the way for potential treatments. Our team at the Center for Research in FOP and Related Disorders continues to lead the world in fibrodysplasia ossificans progressiva research to transform care and improve lives.