What are the other Names for this Condition? (Also known as/Synonyms)

• Diffuse Progressive Ossifying Polymyositis
• Progressive Ossifying Myositis
• Stone Man Syndrome

What is Fibrodysplasia Ossificans Progressiva? (Definition/Background Information)

• Fibrodysplasia Ossificans Progressiva (FOP) is the formation of abnormal bone in the muscle, tendon, ligament, and other connective tissue, where bone is typically not present. The formation of bone in the extraskeletal tissue results in limitation of one’s normal movements
• Any trauma to the muscles or viral illnesses can cause a flare-up of the condition in an affected individual. Fibrodysplasia Ossificans Progressiva is inherited in an autosomal dominant pattern, and hence, only one copy of the defective gene is sufficient to cause this disorder. FOP is caused by mutations in the ACVR1 gene
• Children with FOP are generally born with a malformed big toe. The disorder is so rare that most of the cases are misdiagnosed as cancer
• The diagnosis of Fibrodysplasia Ossificans Progressiva requires a complete evaluation of medical history along with a thorough physical exam. Blood tests during flare-ups are performed to check the elevated levels of alkaline phosphatase and bone specific alkaline phosphatase
• Complications associated with the condition include eating and chewing difficulties due to involvement of the jaw muscles and joints and breathing difficulties due to chest muscles and diaphragm involvement
• Fibrodysplasia Ossificans Progressiva cannot be effectively treated or prevented. Individuals with FOP are typically wheel-chair bound by their twenties and affected by fatal complications of thoracic insufficiency syndrome complications; when the thorax cannot support lung growth or normal respiration

Who gets Fibrodysplasia Ossificans Progressiva? (Age and Sex Distribution)

• Fibrodysplasia Ossificans Progressiva is a very rare disorder. Only 1 in 2 million people are diagnosed with FOP and there are presently around 3,500 affected individuals around the world
• The FOP process starts during early childhood in genetically predisposed individuals
• There are no known ethnic, racial, or gender patterns associated with FOP; the condition is observed worldwide

What are the Risk Factors for Fibrodysplasia Ossificans Progressiva? (Predisposing Factors)

• The most important risk factor for Fibrodysplasia Ossificans Progressiva is a family history of this disorder
• Having a parent with FOP gives their children a 50% chance of inheriting the condition, since it is an autosomal dominant condition

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Fibrodysplasia Ossificans Progressiva? (Etiology)

• Fibrodysplasia Ossificans Progressiva is an autosomal dominant genetic disorder that is the result of mutations in the ACVR1 gene
• ACVR1 protein is found in many tissues of the body including the skeletal muscle and cartilage. The normal function of this gene is to control the growth and development of muscles and bones
• Mutations of this gene results in an overgrowth of bone and cartilage and fusion of joints, resulting in the typical signs and symptoms of FOP

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly functioning gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

What are the Signs and Symptoms of Fibrodysplasia Ossificans Progressiva?

The signs and symptoms associated with Fibrodysplasia Ossificans Progressiva include:

• Children with FOP have deformed big toes
• Flare-ups occur spontaneously or following body trauma such as childhood immunizations, falls while playing, and viral illnesses. The flare up and resulting new bone formation can be painful
• The disorder starts with the involvement of neck and shoulder bones; it then proceeds down to involve the body and limbs
• Formation of tumor-like lumps in the affected regions
• Involvement of chest muscles and diaphragm can cause breathing difficulties
• Decreased mobility and limitation of movements of the affected joints
• Jaw involvement can cause eating and chewing difficulties

How is Fibrodysplasia Ossificans Progressiva Diagnosed?

Fibrodysplasia Ossificans Progressiva is a highly infrequent disorder that may be misdiagnosed for cancer. The diagnostic procedures used for FOP may include:

• Complete evaluation of medical history along with a thorough physical exam
• Blood tests: It may show elevated levels of alkaline phosphatase and bone specific alkaline phosphatase
• Imaging studies such as x-rays and MRI scans

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Fibrodysplasia Ossificans Progressiva?

The complications associated with Fibrodysplasia Ossificans Progressiva include:

• Difficulty speaking or chewing if the mouth is affected by FOP, which may lead to malnutrition
• Breathing can also become difficult if extra bones around the ribs and diaphragm are formed due to FOP

How is Fibrodysplasia Ossificans Progressiva Treated?

Currently, there is no effective treatment available for Fibrodysplasia Ossificans Progressiva.

• Symptomatic treatment is generally offered to the patients
• Surgical procedures makes the condition worse and may result in more robust bone growth
• During flare-ups and new bone formation, pain medication can help decrease pain
• Also, due to flare-ups and restricted movement, school-going children may often need special accommodation

How can Fibrodysplasia Ossificans Progressiva be Prevented?

• Currently, there are no specific methods or guidelines to prevent Fibrodysplasia Ossificans Progressiva, since it is a genetic condition
• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Even though Fibrodysplasia Ossificans Progressiva may not be prevented, the following factors may be considered, which can avoid FOP from worsening. These include:

• Avoid trauma to the muscles or prevent viral illnesses, which can prevent flare-ups
• Avoid intramuscular injections if possible, since this can result in deep trauma. When possible use intravenous method to administer medication
• During surgeries, care must be taken, since even mild injuries to the jaw and neck muscles can result in partial or complete locking (of the jaw)
• Since trauma can cause new bone formation, children should avoid falls, even minor falls

What is the Prognosis of Fibrodysplasia Ossificans Progressiva? (Outcomes/Resolutions)

• Fibrodysplasia Ossificans Progressiva is a debilitating condition. Individuals with FOP are generally wheel-chair bound as they enter into adulthood (early 20s)
• Complications, such as those affecting the respiratory system (thoracic insufficiency syndrome - when normal lung growth or respiration is affected) can be fatal

Additional and Relevant Useful Information for Fibrodysplasia Ossificans Progressiva:

• Surgery to remove excess bone is not an effective treatment, because surgery tends to result in the formation of more bone
• Most of the FOP cases are misdiagnosed because of the rarity of the condition
• Fibrodysplasia Ossificans Progressiva has a long recorded history dating back to the late 17^th century. John Freke, a British physician, has described the condition in detail in 1736