Fibrodysplasia Ossificans Progressiva

 Fibrodysplasia Ossificans Progressiva

DISEASE OVERVIEW

Fibrodysplasia ossificans progressiva (FOP) is a very rare genetic connective tissue disorder characterized by the abnormal development of bone in areas of the body where bone is not normally present (heterotopic ossification), such as the ligaments, tendons, and skeletal muscles. Specifically, this disorder causes the body’s skeletal muscles and soft connective tissues to undergo a metamorphosis, essentially a transformation into bone, progressively locking joints in place and making movement difficult or impossible. Patients with FOP have malformed big toes that are present at birth (congenital). Other skeletal malformations may occur. The abnormal episodic development of bone at multiple soft tissue sites frequently leads to stiffness in affected areas, limited movement, and eventual ankylosis (fusion) of affected joints (neck, back, shoulders, elbows, hips knees, wrists, ankles, jaw – often in that order).

Episodic flare-ups (inflammatory soft tissue swellings) of FOP usually begin during early childhood and progress throughout life. Most cases of FOP occur as the result of a sporadic new mutation and the genetic mutation that results in this disorder has been identified. FOP is caused by the mutation of a gene (ACVR1) in the bone morphogenetic protein (BMP) pathway, which is important during the formation of the skeleton in the embryo and the repair of the skeleton following birth.

Symptoms 

The main symptom of fibrodysplasia ossificans progressiva (FOP) is the gradual replacement of muscles, tendons and ligaments into bone (heterotopic ossification). This process begins at the neck and shoulders in early childhood and progresses throughout the body over time. The development of bone can be rapid in some cases, or very slow in others. Each case is unique.

Symptoms arise during flare-ups, which are your body’s reaction to trauma that could be from an injury, surgery or viral illness like the flu. Swelling, or an increase in size or shape of a part of the body, can be painful. When flare-ups occur, the bone morphogenic protein type 1 receptors fail to stop producing proteins, which causes new bone to form on muscles, tendons and ligaments. After new bone forms, swelling decreases, which could take anywhere from a few days to a month.

A symptom of the condition that leads to an FOP diagnosis is a malformed and short big toe that sometimes grows inward and over the second toe. Growth differences of the big toes are visible at birth, even before other symptoms appear. Nearly 50% of cases of FOP also have malformations of the thumbs similar to the big toe.

Symptoms of fibrodysplasia ossificans progressiva include:

Bone forming on muscles, ligaments and connective tissue.

Decreased mobility (scooting instead of crawling, joint stiffness, locked joints).

Difficulty eating or speaking.

Hearing impairment.

Malformed big toe.

Permanent immobility.

Red to purple, painful and hot to the touch areas of the body that look like tumors.

Scoliosis or kyphosis.

Swelling of soft tissue on the neck, shoulders and back.

As the condition progresses, people diagnosed with FOP may permanently lose the ability to move. They may experience pain and stiffness caused by bone growths that pinch nerves. At this point in a person’s diagnosis, they may be more susceptible to respiratory infection or heart failure.

In severe cases of FOP, people might experience challenges with their cognitive function and ability to learn.

Causes

A mutation of the ACVR1 gene causes fibrodysplasia ossificans progressiva. The ACVR1 gene gives your body instructions to make type 1 receptors for a protein called bone morphogenic protein (BMP) that reside in your muscles and cartilage. BMP controls how bones and muscles grow and develop. The mutation of ACVR1 causes symptoms of fibrodysplasia ossificans progressiva because the receptor, like a light switch, is always on when it should turn off.

Fibrodysplasia ossificans progressiva is an autosomal dominant condition, which means only one biological parent needs to pass the altered gene to the child for them to inherit it. If a parent has the gene that causes fibrodysplasia ossificans progressiva, there’s a 50% chance that the child will inherit the condition.

Most cases of fibrodysplasia ossificans progressiva occur because of a new mutation of the ACVR1 gene (de novo). This happens randomly, and there’s no link to the gene being present in a person’s family history.

Diagnosis

Diagnosis of fibrodysplasia ossificans progressiva begins with a physical examination that identifies the symptoms of the condition, along with reviewing your medical history and performing a genetic test, which is a blood test to identify the gene mutation that causes symptoms. Imaging tests like an X-ray help your healthcare provider examine new bone growth over muscle and connective tissue.

Diagnosis of fibrodysplasia ossificans progressiva can be challenging for healthcare providers. It’s possible to misdiagnose symptoms of FOP as cancer, juvenile fibromatosis (tumors or skin lesions form on soft tissue) or fibrous dysplasia. This occurs because FOP is extremely rare and very few healthcare providers encounter it during their careers. A biopsy of an FOP tumor — when your healthcare provider removes a small portion of the tumor to examine the cells under a microscope — often looks similar to a cancerous tumor.

If your healthcare provider suspects an FOP diagnosis, they won’t perform a diagnostic biopsy because the procedure can cause severe bone growth flare-ups. The most important symptoms that lead to an FOP diagnosis are malformed big toes and soft tissue swelling that forms throughout the body.

Management and Treatment

Treatment for fibrodysplasia ossificans progressiva aims to reduce symptoms, especially flare-ups that ignite the bone-growing process. There’s no cure for FOP but research and clinical trials are progressing to help people diagnosed with the condition. Treatment is unique for each person to address their specific symptoms.

Treatment for FOP could include:

Getting genetic counseling for social, emotional and health-related support.

Participating in occupational therapy to improve physical needs.

Preventative antibiotic therapy to avoid respiratory infections.

Taking medication to reduce swelling and pain associated with flare-ups (corticosteroids, nonsteroidal anti-inflammatory medication, muscle relaxants).

Using mobility equipment like a wheelchair.

Wearing a brace.

Prevention

Preventing symptoms of fibrodysplasia ossificans progressiva involves avoiding trauma to your muscles and tissues. Symptoms flare up when you experience an event that causes stress to your body, like surgery, an injury or an illness. You can reduce your risk of having flare-ups of fibrodysplasia ossificans progressiva symptoms by:

Avoiding situations where you might get an injury, fall or experience physical trauma like a broken bone.

Getting subcutaneous injections (needle enters the fatty tissue of skin) for vaccines instead of intramuscular injections (needle enters the muscle).

Receiving alternative diagnostic tests rather than a biopsy procedure or procedures where tissue needs removing.

Receiving dental procedures that don’t stretch the jaw or use localized anesthetic injections.

Taking preventative steps to avoid viral illnesses like the flu.

You can’t prevent fibrodysplasia ossificans progressiva from occurring because it’s the result of a genetic mutation. To understand the risks of having a child with a genetic condition, talk with your healthcare provider about genetic testing.

Outlook

ibrodysplasia ossificans progressiva is a lifelong condition with no cure. The prognosis (outlook) is poor due to severe symptoms of the condition, including respiratory infections and restricted mobility that becomes worse over time. Life expectancy for someone diagnosed with fibrodysplasia ossificans progressiva is reduced into early adulthood. Most people are completely immobile by age 30. The most common cause of death among people with an FOP diagnosis is a respiratory infection. Research and clinical trials for new treatment options are in progress to help reduce symptoms and prolong the life of people diagnosed with the condition

TYPE OF DOCTOR AND DEPARTMENT: pediatric and adult orthopedics, SPECIALIST CAN DIAGNOSE THISE DISEASE.