Fibrodysplasia Ossificans Progressiva (FOP)

Fibrodysplasia ossificans progressive is a disease where your body exhibits abnormal bone growth and development in ligaments, tendons, and muscles. FOP is the most severe form of heterotopic ossification, which is when there is abnormal, and sometimes nonmalignant, bone growth outside of the skeleton. FOP is caused by a mutation in the AVCR1 gene. This gene controls the production of BMP receptors in the body. The AVCR1 protein basically helps ossification, (growing of bone), take place in the body as one matures from child to adult. Scientists believe that with FOP, the BMP receptors in the body change shape. With that change of shape, the receptors never cease to allow ossification. With the receptors always working, one’s joints, muscles, tendons, ligaments, soft tissue, and so on, turn into bone over time. In FOP, calcium phosphate builds up in intramuscular tissue. Gradually, it turns into hydroxyapatite crystals, thus forming bone.

Inheritance: FOP is an autosomal dominant. However, most cases of the disease are caused by mutations. Mutations occur in people with no family history. A small amount of cases are inherited by one affected parent, or a parent who is a carrier.

  • Malformed big toes
  • Children affected scoot on butt rather than crawl
  • Usually begins in neck, shoulder, back, hips
  • Fever sometimes present during flare ups (new bone formation)

Daily Life:
A person with fibrodysplasia ossificans progressiva usually spends their day avoiding situations of impact where they might be at risk of hitting things, or being hit by things. Families of those with FOP have been known to enroll their child in schools with FOP-friendly environments. Those with FOP usually deal with the pain of their disorder by taking pain relievers to assist with the pain of flare ups. The most difficult parts of living with this disease, in my opinion, are having to deal with the loss of mobility and ability to do the things that they love.

Diagnosis:Fibrodysplasia ossificans progressiva is diagnosed usually in early childhood by a malformation of the big toes. FOP should be diagnosed during neonatal period. Early diagnosis of disease can allow families to avoid aggravation of FOP and even slow progression, providing an improved quality of life. However it is not uncommon for FOP to be misdiagnosed as cancer.

There is no treatment for fibrodysplasia ossificans progressiva. Bisphosphonates and corticosteroids were proven to be somewhat effective during flare ups. Rituximab has also been used. Scientists believe that gene therapy holds a promising future. The best thing for those affected with is to avoid high impact activities, surgery, and intramuscular shots. Some partake in physical therapy, but it does not help in particular.

Scientists are looking into squabimine that is found in sharks to help treat FOP. Squabimine is an antiangiogenic that can prevent growth of blood vessels in cartilaginous tissue. Scientists are also observing fibrodysplasia ossificans progressiva in zebrafish. Another thing that scientists found in those affected with FOP by mutation, as well as those affected by FOP by it being passed down, was that their affected genes were the same. Unfortunately there is still no cure for FOP.

Additional Facts:
Some additional facts not yet covered are that the average age of death is 40, although, ages have ranged from 3 to 75. People’s first flare ups usually take place before they turn 10. Those with FOP cannot have children. Only 1 in every 2 million births is affected with FOP. Anyone can get FOP. Men and women of any race/ethnicity can get FOP. Also, there are/have been approximately 700 known cases of FOP.

Punnett Square:
A Punnett Square does not apply, seeing that most cases of this disease are caused by a mutation.

Pedigree Chart:

WebMD’s “Fibrodyplasia Ossificans Progressiva (FOP)”
International Fibrodysplasia Ossificans Progressiva Association’s “FOP Fact Sheet”
U.S. National Library of Medicine Genetic Home Reference’s “Fibrodysplasia Ossificans Progressiva”; “ACVR1”
National Institutes of Health Office of Rare Diseases Research’s “Fibrodysplasia Ossificans Progressiva”
Medscape Reference’s “Fibrodysplasia Ossificans Treatment”; “Fibrodysplasia Ossificans Management”; “Fibrodysplasia Ossificans Medication”
Wikipedia’s “Fibrodysplasia Ossificans Progressiva”
The Journal of Clinical Investigation’s “The Fibrodysplasia Ossificans Progrgessiva R206H ACVR1 Mutation activates BMP-Independent Chondrogenesis and Zebrafish Embryo Ventralization”’s “Fibrodysplasia Ossificans Progressiva (FOP)”
Everyday Health’s “Fibrodysplasia Ossificans Progressiva (FOP) Causes, Symptoms and Treatment and Related Disorders”
Disabled World’s “Fibrodysplasia Ossificans Progressiva (FOP)- Facts and Information”