Stoneman Syndrome: Causes, Symptoms, Complications, And Treatment

Stoneman Syndrome or Fibrodysplasia ossificans progressiva (FOP) can be described as a rare genetic disease where tissues like tendons and ligaments form bones outside the skeleton system. The muscle tissue and connective tissue ossified ( also known as extra-skeletal or heterotopic bone) which restricts the general movement of the bones and hampers an individual's life.

Since the syndrome is genetic, the development of extra bones can be seen in early childhood itself starting from the neck and proceeding downwards in the body into the limbs. Patients who are born with FOP generally have big malformed toes.

This is a very distinct symptom as none of the other skeleton and muscle-associated diseases does not showcase big malformed toes along with shorter thumbs and other skeletal abnormalities and growths.

First, heterotopic bone in any region of the body can constrain the mobility of an individual which makes it harder to perform daily routine activities. For instance, extra-skeletal in the neck region may cause difficulty in neck and mouth movement. It makes it difficult for the patient to speak, eat or rotate their neck freely.

Second, the growth of heterotopic bone does not stop on its own leading to more severe problems in the later section of life, the bone that once only affects the neck and mouth region will generally make its way downwards in the body from shoulders to backbone and further to limbs. This may put pressure on other bodily organs like the lungs and rib cage making it difficult for the patient to breathe.

Third, abnormal growth may make an individual's overall body fragile and vulnerable to external damage. Any physical trauma to the muscles like a fall or invasive medical procedures can cause myositis ( episodes of muscle swelling and inflammation) and increase the process of ossification in the affected area.

In females, the heterotopic bone in limbs or lower back can make it difficult to conceive, and continue with the pregnancy and childbirth, however, it is not impossible to conceive. But it is advised by medical professionals to avoid any pressure on your body to avoid any flare-ups.

ACVR1gene is found in many tissues of the body including cartilage and skeletal muscle is responsible for the mapping of bone morphogenetic protein (BMP) type I receptors. BMP is a member of the protein family which looks after the infrastructure of the whole body by maintaining the right balance of morphogenesis, cellular lineage commitment, proliferation, differentiation, and apoptosis of various types of cells throughout the body.

ACVR1 gene also looks after the development of the muscles and bones including ossification. Usually, the process of ossification aids gradual replacement of cartilage by bone which is normal in the skeletal maturation of a healthy individual.

Mutations in the ACVR1 gene can cause disruption in mechanisms that control the activities of the receptors. The abnormal activation of receptors leads to more than the required ossification of bone morphogenetic protein leading to fibrodysplasia ossificans progressiva.

The good news is the cases of fibrodysplasia ossificans are very low, the probability of the case is 1 in 2 million people worldwide. This is because the illness of Stoneman Syndrome runs in autosomal dominant patterns, which means that one copy of the altered gene in each cell is enough to create the malfunction.

The nature of the genetic disorder makes it both easy and difficult to identify. Since FOP is quite rare and less known by the general public, one might confuse it with less severe other muscular disorders. On the other hand, its distinct symptoms make it easy to diagnose.If a person or blood is related to a person who has this rare genetic disorder, it is quite susceptible that it will transfer to your off-springs.

One can see it by close examination of the toes and thumbs of their newborn child. Infants with this syndrome are born with malformed big toes and in some cases malformed thumbs.

Other than that here are some of the symptoms which can be shown by the child as they grow with Stoneman Syndrome:

• Restricted movements of the joints, especially neck and shoulders at the initial stages.
• Deformed spine.
• Frequent imbalance while moving followed by low-grade fever, inflammation, and joint pain.
• Surface reflection of abnormal bone growth throughout the body ( except the tongue, diaphragm, extraocular muscles, cardiac muscle, and smooth muscle).
• Difficulty in breathing, eating, and speaking.
• Hearing impairment ( rare).
• Visible swelling in the affected area.

These symptoms will get more severe as the child grows, as the tissues not only ossify in the upper region of the body, but also makes their way downwards to the trunk, back, hips, and limbs until a person completely gets immobilized.

Diagnosis of a rare genetic disease can be a challenging task. At initial stages, cases of FOP can be confused with other aggressive muscular illnesses like juvenile fibromatosis, cancer, and fibrous dysplasia. The only symptom that makes it different from other conditions is malformed big toes.

Like every other medical diagnosis, your healthcare professional will examine your medical and your family medical history to look for any genetic pattern, followed by a series of physical examinations and laboratory tests. Your laboratory test may include imaging tests such as X-ray and MRI and a genetic testing registry (GTR).

Imaging tests will help the doctor to see the overall growth of the heterotopic bone whereas GTR will direct the doctor to choose appropriate genetic tests for this condition. GTR is conducted by a group of medical professionals that majorly deals with research and analysis of such rare conditions and it includes a series of questions for both patient and the medical team.

Genetic disorders like fibrodysplasia ossificans progressiva do not have an effective cure till now, and since the removal of the bone will only lead to the growth of new and more painful heterotopic bone, medical professionals have come up with a couple of medications that slow down the growth and intensity of ossification:

• High dosage of corticosteroids like Prednisone to reduce pain and swelling flare-up. seen in the early stages. It is recommended to be within 24hrs of the first flare-up, before Nonsteroidal anti-inflammatory drugs (NSAIDs) which need to be given between flare-ups.
• Muscle relaxants.
• Mast cell inhibitors.
• Aminobisphosphonates.
• Assistive devices such as braces or special shoes to help with walking.
• Occupational therapy.

One of the things that needed to be monitored in the treatment duration is things that can increase the ossification and physical discomfort.

Treatments and medical diagnoses associated with bone such as biopsy, Intramuscular injections (immunizations) or injections, and jaw stretching during dental procedures must be avoided, as it can damage the skeletal system which can flare up the process of ossification in the affected area.

Avoid getting hurt, it's not easy when your mobility is manipulated but blunt trauma or injury can cause a flare-up in the heterotopic bone, any physical activity that has a risk of fall and other physical injuries must be restricted.

FOP can be dangerous for pregnant women, it is advised to avoid childbirth if you have this genetic disorder for majorly two reasons, firstly your malfunction genetics can be transferred into your offspring making their survival difficult for the rest of their lives. Secondly, The increasing fetus in your womb can increase the risk of flare-ups which can be life-threatening for both mother and baby.

FOP patients often experience unpredictable episodes of soft tissue pain, swelling, reduced movement, and stiffness, which are known as ‘flare‐ups’. Even though flare-ups can be relieved without any specific course of treatment, it needs a certain amount of management to relieve discomfort and slow down the formation of heterotopic ossification.

One can easily identify FOP flare-ups by looking at symptoms like a sudden pain, redness, bumpy/lumpy swelling, stiffness, and warmth in the affected area. Flare-ups can be triggered with daily routine incidents and activities like physical injury or exhaustion, muscular stretching; any medical procedures like intramuscular injections, dental procedures, or Biopsy, or any viral or bacterial infection.

You can manage your flare-up and its discomfort by avoiding trigger points and following medical prescriptions given by your doctor. Keep track of your episodes and your daily routine to have a better understanding of your illness. Also, share your concerns and track records with your doctors to get the best-recommended treatment.

Apart from pain, inflammation, and swelling, the extra bone may expand its way to the chest suffocation organs like lungs, heart, esophagus, etc. This also hampers your ability to speak, eat or even walk in the later section of life, and in severe cases, it can cause respiratory infections and heart failure.

In a few cases, heterotopic bone can also cause curves in the spine. Depending upon the growth side, it can be side to side or top to bottom. This can make it difficult for an individual to walk and perform daily routine jobs.

Summary: Stoneman Syndrome or Fibrodysplasia ossificans progressiva (FOP) can be described as a rare genetic disease where tissues like tendons and ligaments form bones outside the skeleton system. Caused by mutations in the ACVR1 gene, FOP can be detected from the child’s birth having a deformed spine and difficulty in locomotion.