What is Fibrodysplasia Ossificans Progressiva (Stone Man Disease)?
Fibrodysplasia ossificans progressiva is a very unusual genetic disorder that involves the hardening of soft tissues like ligaments, tendons, and muscles. It’s a type of disorder that’s passed down through families. This condition causes the body to produce tissue which is not just hardened calcium phosphate, but indeed new bone that looks like it’s been formed by bone-building cells through a process called endochondral ossification.
Most people born with Fibrodysplasia ossificans progressiva can move their joints normally, but in their thirties, they start facing joint problems as the hardened tissues slowly join up with normal bones. When these hard tissues merge with normal bones, it’s like a bridge is formed between them. It’s also important to avoid causing any injury to the soft tissues because it can trigger the formation of these hard, bone-like structures. This also means invasive procedures, such as injections, surgery, and biopsy, should be avoided to prevent this from happening.
For a long time, diagnosing Fibrodysplasia ossificans progressiva was tough because there were no reliable markers in the urine or blood that could indicate its presence. It’s discovered that the condition is caused by a mutation in the ACVR1/ALK2 gene located on chromosome 2, which involves proteins that contribute to the formation of the abnormal hard tissue in the soft tissues. The shoulders, neck, and spine are often the most affected areas, and the average lifespan for people with this condition is around 40 years. The main cause of death is usually due to difficulties in the chest area and related complications. The primary way to diagnose this condition is through a method called PCR, which checks for any genetic mutations related to Fibrodysplasia ossificans progressiva.
What Causes Fibrodysplasia Ossificans Progressiva (Stone Man Disease)?
Fibrodysplasia ossificans progressiva is a rare disorder caused by a specific mutation, or change, in a gene named ACVR1/ALK2 located on chromosome 2. This gene is part of a process that helps to form bone, and it is seen in both inherited and random cases of the disease that aren’t traced back to family history.
The ACVR1/ALK2 gene helps to create a protein known as ALK2, which sticks on the outer surface of cells and binds with other molecules involved in bone formation.
These molecules, known as bone morphogenetic proteins, can trigger the growth of bone in the muscles—something that typically happens in cases of fibrodysplasia ossificans progressiva.
The majority of people with this disease have a specific change in the ACVR1/ALK2 gene that leads to an altered ALK2 protein. This specific alteration is caused by a single unit change (from guanine to adenine) at a certain point in the gene.
In addition to this, other changes or mutations have been found on different points of the ACVR1/ALK2 gene. These mutations affect the production and functions of two important parts of the ALK2 protein. They change how the protein works within cells, which is crucial for understanding how the disease progresses.
Risk Factors and Frequency for Fibrodysplasia Ossificans Progressiva (Stone Man Disease)
Fibrodysplasia ossificans progressiva is a condition that affects about one in every 2 million people around the world. It’s important to note that anyone can develop this condition, regardless of their race, gender or where they live.
Signs and Symptoms of Fibrodysplasia Ossificans Progressiva (Stone Man Disease)
Fibrodysplasia ossificans progressiva (FOP) is a rare condition where soft tissues progressively turn into bone. Around 90% of people with FOP have notable issues with their big toes at birth, but they generally appear normal otherwise, with normal joint movement. However, as they grow older, changes begin to occur.
- In the first ten years of life, the process of soft tissues becoming bone – known as heterotopic ossification – starts. In most cases, this leads to occasional flares of painful swelling in soft tissues.
- By the time these individuals reach their third decade of life, the abnormal bone growth fuses with their normal bones. This results in joint immobility, most commonly affecting the neck, spine, and shoulders (over 80% of cases in those under 15).
- As time passes, more joints become affected, including the wrists, ankles, elbows, knees, hips, and jaw. This happens gradually until they are around 40 years old. The disability progresses from the top of the body to the bottom, from near to far, and from back to front – starting from neck, spine, shoulders, then to elbow, knee, hip, jaw and finally to wrists and ankles.
Ultimately, these individuals become reliant on wheelchairs and require lifelong assistance with daily activities. On average, people with FOP live until they’re about 40 years old.
Testing for Fibrodysplasia Ossificans Progressiva (Stone Man Disease)
Diagnosing a condition known as Fibrodysplasia Ossificans Progressiva mainly involves the analysis of genetic mutations. This means that doctors look for changes in a specific gene using a process called Sanger sequencing. This analysis is typically performed on products resulting from a technique called PCR, which is a way of creating many copies of a certain piece of DNA for easier studying.
However, the bones that grow in abnormal places (termed heterotopic bone) due to this disease look very similar to normal bones in routine lab tests, so the disease is primarily identified by the abnormal location of this bone growth.
During periods of worsened symptoms, often referred to as flare-ups, there may be increased activity of a substance in the blood called serum alkaline phosphatase, as well as elevated levels of growth factors in the urine. These growth factors, specifically known as basic fibroblast growth factors, play a pivotal role in the formation and growth of new blood vessels, a process that precedes new bone formation during the early stages of the disease.
Imaging, such as X-rays, CT scans, and MRIs can also be very useful for diagnosis. Regular X-rays can show the abnormal bone formation after it has occurred. CT scans provide more detailed images and can show the characteristic abnormalities of these misplaced bones. MRIs are beneficial in showing the early changes that happen before the bone forms, such as swelling of the tissues and distortions in the shape of the skeleton. However, it’s important to note that Fibrodysplasia Ossificans Progressiva cannot be diagnosed before birth.
Treatment Options for Fibrodysplasia Ossificans Progressiva (Stone Man Disease)
Fibrodysplasia ossificans progressiva is a condition that doesn’t have one single effective treatment. However, there are a few options that can help to manage the symptoms during flare-ups. Steroids such as prednisone can be used for a short while, but it’s not a good idea to use them a lot. Other medications like mast cell inhibitors, NSAIDS, amino bisphosphonates, and COX-2 inhibitors can help with flare-ups that come up later.
Patients might also find some relief from muscle spasms by using muscle relaxants in small amounts. Other potential ways to treat the condition might include stopping a specific gene pathway (ACVR1ALK2) which could prevent abnormal bone formation, or slowing down the activity of certain cells which could disrupt the conditions needed for the bone growth associated with this condition.
As we understand more about fibrodysplasia ossificans progressiva, researchers are finding new potential targets for drugs which could help to manage the condition. Several drugs are currently in clinical trials, including imatinib, a human anti-activin A-neutralizing antibody, dorsomorphin, palovarotene, and rapamyÂcin. These trials might result in effective new treatments in the near future.
While surgery is sometimes used to treat medical conditions, it’s generally not recommended for patients with fibrodysplasia ossificans progressiva.
What else can Fibrodysplasia Ossificans Progressiva (Stone Man Disease) be?
The fibrodysplasia ossificans progressiva which is a rare disease can sometimes be mistaken for other conditions. Here are some such conditions that might be considered:
- Isolated congenital malformations
- Juvenile bunions
- Sarcoma
- Desmoid tumor
- Aggressive juvenile fibromatosis
- Lymphedema
It’s important that doctors carefully analyze the symptoms to avoid misdiagnosis.
What to expect with Fibrodysplasia Ossificans Progressiva (Stone Man Disease)
Fibrodysplasia ossificans progressiva is a medical condition that often has a serious outlook because it can lead to complicated health issues such as pneumonia and right-sided heart failure. Pneumonia is a lung infection, and right-sided heart failure refers to the heart’s inability to properly pump blood. Most fatalities in these cases are primarily due to a condition known as thoracic insufficiency syndrome and problems related to this syndrome. Thoracic insufficiency syndrome is a decline in the chest wall’s ability to support normal breathing.
Possible Complications When Diagnosed with Fibrodysplasia Ossificans Progressiva (Stone Man Disease)
Common problems related to this sickness might include:
- Respiratory infections, or problems with the breathing system
- Joint issues, or problems moving the body well
- Heart and lung complications, like thoracic insufficiency syndrome and right-side congestive heart failure
- Swelling under the jaw
- Temporomandibular joint ankylosis, or a stiff jaw
- Conductive hearing loss, or difficulty hearing
Preventing Fibrodysplasia Ossificans Progressiva (Stone Man Disease)
Patients who show noticeable deformities in their toes linked to a condition called fibrodysplasia ossificans progressiva, need to be quickly identified and checked for this disease. Fibrodysplasia ossificans progressiva is a serious disorder that can greatly affect a person’s quality of life and may lead to early death. Identifying the disease early on can help increase the patients survival rate. Once the disease has been diagnosed, patients should avoid procedures that go beneath the skin, such as injections or surgery, because these could cause new bone to form. Additionally, proper therapy for deformities and stiffness in the joints can help patients to maintain the best level of function possible.
