Introduction

Fibrodysplasia ossificans progressiva (FOP), also known as myositis ossificans or “stone man syndrome” is an extremely rare genetic disorder that affects 1 of 2 million people, and it is not determined by race, gender, or geographical distribution.¹ It promotes abnormal development of bones in the skeletal muscles, tendons, and ligaments and causes a restriction in movement, leading to significant disability and discomfort.²

Currently, there’s no cure for FOP, so treatment revolves around managing its impact. Understanding the management of this condition is important for improving the well-being of those affected. 

This article delves into the causes, symptoms, treatment and management strategies to effectively cope with FOP.

Understanding fibrodysplasia ossificans progressiva

Causes of fibrodysplasia ossificans progressiva

FOP is caused by a mutation in the ACVR1/ALK2 (Activin A receptor type 1/ Activin-like kinase 2) gene located on chromosome 2, which plays a crucial role in the growth and development of bones and muscles.² It is a type 1 receptor for a protein known as bone morphogenic protein (BMP). The BMPs cause the body’s connective tissues to transform into new bones affecting mostly the shoulders, neck, and spine. The process of this new bone formation is called “heterotopic ossification”.⁶

Symptoms of fibrodysplasia ossificans progressiva

One of the first visible signs of FOP is a malformation of the big toes, which can be noted at the birth of a child. As the child grows, painful flare-ups occur, especially in the first few decades of life. These flare-ups lead to the formation of extra bones in the skeletal muscles, tendons, and ligaments and can be triggered by trauma, intramuscular injections, and even surgical procedures.^1,7

Depending on the part of the body ossified the symptoms of FOP include:

• Painful and highly inflammatory soft tissue swelling³
• Limited mobility (difficulty walking and sitting, stiffness)
• Anaemia
• Alopecia (Hair loss)
• Difficulty eating, breathing, and speaking
• Hearing impairment
• Joint fusion
• Malformed and short big toes

In some cases, FOP leads to permanent immobility. Affected individuals are likely to be confined in a wheelchair at age 30.

Diagnosis of fibrodysplasia ossificans progressiva

The clinical diagnosis of fibrodysplasia ossificans progressiva can be challenging due to the rarity and initial representation of the symptoms. There's a possibility of this syndrome being mistaken for other health conditions like aggressive juvenile fibromatosis, lymphoedema, or soft tissue sarcoma.⁴ 

About 90% of FOP patients worldwide have been misdiagnosed and 67% have been mistreated causing pains and irreparable damage for those experiencing the syndrome.¹ If your healthcare provider suspects FOP, there’s no need to go through the diagnostic biopsies process as it worsens the situation.

Genetic testing

It is now easy to access definitive genetic testing that identifies the mutations of the ACVR1 gene. Before the manifestation of heterotopic ossification (HO), clinicians can diagnose FOP early through genetic testing.

Genetic testing is highly accurate and clinicians can confirm the diagnosis faster. However, they need to understand the early signs of FOP, like malformed large toes and swelling of the soft tissues, before heterotopic ossification creeps in. 

Imaging analysis

Imaging analysis (CT and MRI) is another method for diagnosing FOP in addition to genetic testing.¹ Imaging techniques assess the extent of bone formation and monitor disease progression. They also help to differentiate between soft tissues and newly formed bones. 

Early and accurate diagnosis not only prevents harmful treatment but also sets the stage for better management and is crucial for extending the lives of those affected by this condition. Therefore parents, caregivers, and paediatricians should watch out for deformities of great toes and swelling of soft tissues that appear on the head, neck, and upper back in children.

Management & treatment strategies for fibrodysplasia ossificans progressiva (FOP)

There’s no permanent cure for fibrodysplasia ossificans progressiva (FOP) yet. However, further research is ongoing and many management strategies are based on expert opinion rather than conclusive evidence.^5,8

Some of these management strategies focus on reducing flare-ups, minimising symptoms, and maintaining the best quality of life. You can manage this condition by:

Using mobility equipment

As the condition progresses, affected individuals may need supportive devices such as wheelchairs, walkers, and braces to maintain independence and mobility.

Avoiding surgery

Surgery is generally avoided in FOP patients as it often leads to further heterotopic ossifications. 

However, if essential, such as in life-threatening conditions and complications, they should be performed in specialised FOP centres with extreme caution. Every stage of the procedure requires experienced and specialised team members with the needed skills to make the surgery successful.

Engaging in safe physical activities

Children diagnosed with FOP should be observed closely so they don’t engage in hard play that can lead to falls and injuries. Parents and caregivers must ensure the environment is safe for play. They can also use protective headgear to minimise any injury that may occur.

Consult a healthcare personnel before vaccine administration

Fibrodysplasia ossificans progressivia is a rare condition that needs the expertise of knowledgeable healthcare practitioners. It is advised that intramuscular injections and muscle biopsies should be avoided as they can cause flare-ups.⁵

Therefore, the recommended guidelines of the International Clinical Council on FOP (ICC-FOP) should be followed before administering vaccines to FOP patients.

Pharmaceutical treatments

Corticosteroids are prescribed during the early stages of flare-ups, especially when soft tissue swelling is detected. It is administered at the onset of a flare-up for a short period of 4-5 days and it helps reduce inflammation. However, due to the potential side effects of corticosteroids' long-term use, it’s advised to be used sparingly.⁵

NSAIDs (Non-steroidal anti-inflammatory drugs) are also used to manage pain and reduce inflammation associated with FOP flare-ups.

Additionally, in August 2023, the FDA (Food and Drug Administration) approved “sohonus (palovarotene)” capsules for treating FOP in children aged 8 years and older females, and 10 years and older males.

Psychosocial support

Dealing with a chronic and progressive condition like FOP can be quite challenging as it can lead to emotional stress and mental health issues. 

Counselling, support groups, and mental health services should provide needed support for patients and their families. This will help improve mental well-being and provide emotional relief to affected individuals.

FAQs

What gene is responsible for FOP?

FOP is caused by a mutation in the bone morphogenic protein (BMP) gene known as ACVR1.

What muscles are affected by FOP?

The specific muscles affected and the rate of progression varies among individuals. The ossification often begins from the neck to the spine and shoulder. It then progresses to other parts.

Is there a cure for FOP?

Currently, there is no cure for fibrodysplasia ossifications progressiva (FOP) because it's a complex genetic disorder. However, the condition can be treated and managed.

What age does FOP start?

Fibrodysplasia ossificans progressiva (FOP) begins to show symptoms in early childhood with a median age of 5 years.

How long do people with FOP live?

The estimated life expectancy for people living with fibrodysplasia ossificans progressiva (FOP) is 56 years of age. However, some affected individuals still live longer than that.⁴

What is the most common cause of death of FOP patients?

The death of individuals affected with fibrodysplasia ossificans progressiva is mostly a result of cardiorespiratory failure from thoracic insufficiency syndrome and pneumonia.

Summary

Fibrodysplasia ossificans progressiva (FOP) is a rare and challenging condition characterised by congenital malformations of large toes and swelling of soft tissues. However, there’s no permanent treatment for this condition yet because it’s a condition that requires special care. The treatment of FOP is currently limited to managing the symptoms and preventing flare-ups. 

Researchers are still doing their best to ensure the availability of effective medication to prevent heterotopic ossifications in fibrodysplasia ossificans progressiva. If you notice any symptoms of FOP in your child at birth, do reach out to your health provider for diagnosis.