Genetic mutation: People with fibrodysplasia ossificans progressiva (FOP) are born with mutations in the activin A receptor, type I (ACVR1) gene. Normally, this gene provides the body with instructions on how to produce the activin receptor type I protein, which is a member of a protein family called bone morphogenetic protein (BMP) type I receptors. The ACVR1 protein is present in many body tissues, including the skeletal muscles and cartilage. The protein helps regulate the growth and development of muscles and bones. It also helps control the gradual replacement of cartilage by bone that occurs when a person grows into an adult.
When there is a mutation in the ACVR1 gene, researchers believe that it causes too much bone to grow, resulting in the signs and symptoms of FOP.
Random occurrence: Nearly all cases of FOP occur randomly and are not inherited. Instead, the genetic mutation randomly occurs during the development of the egg, sperm, or embryo.
Inheritance: When FOP is inherited, it is passed down as an autosomal dominant trait. This means that one copy of the mutated gene (from just one parent) is enough for a child to develop the disorder. However, FOP is rarely inherited because most people with the disorder are unable to have children.
In most cases, an accurate diagnosis of fibrodysplasia ossificans progressiva (FOP) can be made based on the patient's characteristic signs and symptoms of the disorder. Young children typically have malformed big toes and painful, tumor-like swellings on the head, neck, and/or back.
However, researchers believe that FOP is often misdiagnosed because it is a rare disease, affecting about one out of two million people worldwide. Cancer, aggressive juvenile fibromatosis, and progressive osseous heteroplasia are three of the most common misdiagnoses. Experts estimate that the rate of misdiagnosis of FOP may be 80% or higher.
signs and symptoms
General: Since FOP is a progressive disease, it typically becomes more severe and affects more areas of the body as time goes on. However, disease progression and the rate at which new bone forms vary among patients.
Malformed big toes: People with fibrodysplasia ossificans progressiva (FOP) are typically born with malformed toes. The big toe is typically shorter than normal and abnormally turned outward in a position called a valgus deviation.
Excessive bone growth: During early childhood, most people with FOP develop painful tumor-like swellings (called fibrous nodules) that are visible on the neck, shoulders, and back. These nodules eventually transform into bone in a process called heterotopic ossification. Over time, bone starts to replace the body's muscles and connective tissues along the trunk and limbs of the body.
When the body starts to generate new bone, the patient typically experiences a painful flare-up, or sudden worsening of symptoms, that causes tissue swelling and joint stiffness. During this process, calcium phosphate builds up in the intramuscular tissue. Bone forms once this material transforms into hydroxyapatite crystals. Some people may also experience low-grade fevers. This is because fevers are part of an inflammatory reaction. Flare-ups may last as long as 6-8 weeks.
Flare-ups typically develop after a person experiences trauma to the body, such as a fall. Illnesses, such as the flu, may also trigger flare-ups. However, flare-ups may develop without any known trigger.
Most FOP patients are bedridden by the time they reach their 30s, and they usually die before age 40.
General: There are many complications associated with fibrodysplasia ossificans progressiva (FOP) because the condition leads to progressive loss of mobility as more and more parts of the body become affected. Frequent illnesses or trauma to the body may speed up the disease progression. Complications vary among patients with FOP, depending on which part of the body is affected.
Breathing problems: If extra bone replaces the tissues over the rib cage, people may not be able to expand their lungs normally. As a result, breathing may be difficult.
Difficulty speaking or eating: If extra bone develops in the jaw joints, a person may have difficulty speaking or eating. In some cases, difficulty eating may lead to malnutrition.
Limited mobility: As bone replaces muscles and connective tissues, people typically experience limited mobility in the affected parts of their bodies. As a result, everyday activities, such as walking and getting dressed, may be challenging. Most FOP patients are bedridden by the time they reach 30 years of age.
Skin sores: People with FOP, especially adults, often develop pressure sores on their skin. Sore and broken skin may develop if extra bone puts pressure on the skin. Therefore, people with FOP should wear protective padding over bony bumps on their bodies and they are encouraged to change sitting positions frequently. People who sit for many hours during the day are encouraged to use well-padded seat cushions.
Skin sores may also develop if the skin becomes moist or sweaty in difficult-to-reach areas. Because people with FOP often have limited mobility of their joints, they may be unable to properly clean the skin. As a result, bacterial or fungal infections may develop on the skin.
Nearly all cases of fibrodysplasia ossificans progressiva (FOP) occur randomly with no family history of the disorder. Although, it is possible for people who have the disorder to pass the condition to their children, it is rarely inherited because most people with FOP are unable to have children.