Fibrodysplasia Ossificans Progressive (FOP) is a rare disorder in which the connective tissues of the body, including tendons, muscles, and ligaments, are gradually replaced by bone in a process called ossification.
The condition is present right from birth, but symptoms may not become evident until early childhood. Ossification may happen randomly or after an injury.
Keep reading to understand more about FOP and why early diagnosis is crucial. We’ll also share the name of the organizations supporting this disease.
Fibrodysplasia Ossificans Progressive Or FOP Symptoms:
FOP, also known as Stone Man Syndrome, becomes noticeable early in childhood. Babies are mostly born with short, malformed big toes. Joint and bone problems make it hard for infants to learn to crawl. Nearly 50 percent of people with FOP also have abnormal thumbs (1).
Overgrowth of the bone tends to start in the neck and shoulders, causing alternating bouts of painful inflammation. The misery is sometimes accompanied by a low-grade fever.
The syndrome progresses at a different rate for each person. Eventually, it may affect the back, trunk, hips, and limbs. The following symptoms may appear:
The growth of a bone in the chest can restrict breathing, increasing the risk of respiratory infection. Any viral illness can trigger a flare-up.
- Movement of the body parts can become severely restricted as the bone grows into joints.
- The spine can become fused or deformed.
- The limited movement may cause balance and coordination issues that can result in injury due to falling.
- Even minor damage can cause severe inflammation and bone growth.
- Limited mobility of the jaw can make it hard to eat. This can result in malnutrition and weight loss. Talking can also be severe.
- Approximately half of the people with FOP experience hearing impairment (2).
- Reduced blood flow can result in pooling of the blood in the arms or legs, causing visible swelling.
FOP doesn’t cause extra bone growth to the:
- Cardiac muscle.
- Smooth muscle.
- Extraocular muscles.
An individual with FOP can eventually become immobilized.
The first case of FOP was reported in the seventeenth century. It was initially known as myositis ossificans progressive.
The disease was thought to be caused by muscular inflammation (myositis) that results in bone formation (3).
Later, FOP was renamed by Victor A. McKusick in 1970, following the discovery that the soft tissue other than muscles were also impacted by the disorder.
The best-known case is that of Harry Eastlack (1933–1973).
Most of the people who are born with FOP have the condition due to a random genetic mutation.
As the disease continues to progress, the patient is unable to perform simple tasks of daily life like cooking or bathing.
A person only requires one affected gene to have FOP. Most cases occur because of a random mutation.
People rarely develop the condition because they inherited an abnormal gene from one of their parents. In genetics, this is called an autosomal dominant disorder (4).
A person with FOP has a 50 percent chance of passing it on to his or her kid (5).
Medical experts at the University of Pennsylvania identified the gene mutation responsible for the disease. They found a receptor on chromosome 2 called Activin Receptor Type IA (ACVR1) (6).
ACVR1 is located in the gene that encodes bone morphogenic proteins (BMP), which assist form and repair the skeleton, beginning when an embryo is still forming (7).
Professionals believe the mutation in the gene prevents these receptors from being turned off. This allows the uncontrolled bone to form in parts of the body where it usually would not seem throughout a person’s life.
Fibrodysplasia Ossificans Progressiva is a sporadic condition. The diagnosis of fibrodysplasia ossificans progressiva can be challenging.
It’s not unusual for the disease to initially be misdiagnosed as a form of cancer or a condition called Aggressive Juvenile Fibromatosis (8).
Early in the case of FOP, if tissue is biopsied and examined under a microscope, it may share some connections with aggressive juvenile fibromatosis.
However, in the latter condition, the wounds don’t progress to fully formed bone as they do in FOP. This can help researchers to make a distinction between the two.
One important diagnostic clue that would lead a doctor to suspect FOP is the presence of short and malformed big toes.
If a tissue biopsy is uncertain, a clinical exam of a child can help a medic rule out aggressive juvenile fibromatosis.
Kids with the condition don’t have the congenital malformation of toes or fingers, but a child with FOP nearly always does.
Another disorder, Progressive Osseous Heteroplasia, can also be confused with fibrodysplasia ossificans progressiva (9).
The keynote, when making the diagnosis, is that bone growth in progressive osseous heteroplasia usually starts on the skin, not under it.
These osseous plaques on the skin surface distinguish the condition from the tender nodules that happen in FOP.
Other tests a specialist may use if they suspect FOP include:
- Radiologic tests such as computed tomography(CT) or bone scintigraphy (bone scan) to look for skeletal changes (10,11).
- A detailed medical history and physical exam.
- Lab tests to measure the alkaline phosphatase levels.
- Genetic testing to look for mutations.
If the diagnosis of the FOP is suspected, experts will generally try to avoid any invasive tests, procedures, or biopsies because of trauma results typically in new bone formation in someone with the condition.
While the disorder doesn’t typically run in families, parents who have a kid diagnosed with FOP may find genetic counseling useful.
What Are The Treatment Options?
There’s no cure for FOP chronic, progressive disorder. However, treatment for particular symptoms can improve the quality of life. Some of these are:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) (12).
- Corticosteroids to decrease pain and swelling during flare-ups.
- Occupational therapy.
- Assistive devices like braces or special shoes to help with walking.
There’s nothing that allows the new bones to go away. Surgery would lead to more bone growth.
An essential part of the treatment plan has to do with what to avoid in such a case. A biopsy can cause rapid bone growth in the area.
Intramuscular injections, like most immunizations, can also cause problems. Dental work must be done with great caution, avoid injections, and stretching of the jaw.
Blunt trauma or injury because of falling can cause a flare-up. Any physical activities that grow these risks should be avoided.
Excess formation of bone may be seen on imaging tests like X-ray and MRI, but are not required for diagnosis. It can be confirmed with genetic testing.
The rate of misdiagnosis could be as high as 80 percent. The most common misdiagnoses are aggressive juvenile fibromatosis, cancer, and fibrous dysplasia (13).
Earlier, the symptom that can distinguish FOP from these other disorders is a deformed big toe.
FOP can be hazardous during pregnancy. This can increase the chances of flare-ups and complications for both mothers and infants.
FOP Patient Life Expectancy:
As mentioned earlier, there’s no cure for FOP. Treatment is mostly helpful, and the progression of the condition is usually reasonably unpredictable.
Because it’s such a rare condition, most of the people have never heard of FOP.
The progression rate varies from person to person, and it is difficult to predict. Some individuals go months or even years without an outbreak.
Ossification often occurs randomly and can’t be prevented entirely. It can occur in response to inflammation, injury, and illness.
Hence, recommendations about lifestyle, activity, preventative care and interventions must be made beginning in childhood.
Invasive procedures or surgeries to remove areas of abnormal bone growth are not permissible, as the trauma of surgery invariably results in the development of further ossification.
If surgery is vital, then the most minimally-invasive method possible should be used. Patients with FOP disorder also may need special anesthesia considerations.
FOP can be severely disabling. Most of the people with FOP will require a wheelchair by the time they reach their 20s. The median life expectancy for people with FOP is 40 years (14).
The Bottom Line:
FOP is a rare condition and difficult to diagnose. There are about 800 cases worldwide, with 285 of them in the United States (15).
Gender, ethnicity, and race play no role in FOP. Unless you have a parent with this disorder, there’s no way to assess your risk of developing the illness.
FOP is not contagious, but still, it is crucial to educate people about the profound effects of this rare condition.
Organizations that can raise awareness for FOP. They can share the details of programs and services. Here are a few:
- Canadian FOP Network (16).
- International Fibrodysplasia Ossificans Progressiva Association (IFOPA) (17).
- FOP Friends(U.K.) (18).
Some of the foundations that raise the awareness for rare diseases in general are:
- National Organization for Rare Disorders (NORD) (19).
- Rare Disease Foundation (20).
- Rare Action Network (RAN) (21).
It’s also essential to get the correct diagnosis as soon as possible. That’s because specific tests and treatments for other disorders can cause flare-ups and encourage bone growth.
There have been several clinical trials recently to develop better treatment options for people with FOP (22).