Fibrodysplasia ossificans progressiva (FOP) is a condition that is characterised by the formation of bones in connective tissues such as ligaments, tendons, and muscles.^1,2 This process of abnormal bone formation is called heterotopic ossification (HO).³ It can occur in any part of the body, and most commonly affects the neck, trunk, and upper limbs.

FOP is a genetic condition and is caused by genetic changes in the ACVR1 gene that controls bone growth. The genetic changes lead to development of bone in areas where bone is not normally present.² As new bones gradually replace connective tissues, it can cause stiffness, pain, limits movement, and affects the function of organs.^1-3

The two classical clinical features of FOP are the malformation of the great toes (first toe on each foot) and heterotopic ossification that worsens over time (progressive HO).^3,4 Most individuals with FOP have these classical features and it has been associated with having a specific genetic variant in the ACVR1 gene. Individuals with other ACVR1 genetic variants often present with slightly different symptoms, which is known as atypical FOP.⁴

Synonyms: FOP, myositis ossificans progressiva.⁵

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:337 Fibrodysplasia ossificans progressiva

ICD-11: FB31.1 Fibrodysplasia ossificans progressiva

There are usually no signs of FOP visible at birth, other than malformations of the great toes (the first toe on each foot), where the toe is short, bent, and curved inwards towards other toes.¹ Those with atypical FOP may not have these toe malformations or may have more toes impacted.⁴

During childhood, most individuals develop episodes of painful, inflammatory soft tissue swellings, known as “flare-ups”.¹ Flare-ups can happen spontaneously or triggered by trauma/injury (such as falls, bruises, intramuscular injections, dental work, muscle fatigue, surgery, viral illness).¹ Flare-ups can lead to heterotopic ossification (HO) and formation of new bones.

HO tends to spread through the body as a person ages. It usually starts in the upper back, spine, head and neck, shoulders and hips; and spreads to the front of the body, limbs, hands and feet.¹ HO can make it hard to move and walk, and most individuals become wheelchair dependent over time. For those with atypical FOP, this can vary from mild or late onset to aggressively progressing.⁴

The symptoms and severity of FOP can vary between individuals, depending on the area of the body that is affected and their genetic variant. Other common symptoms of FOP include:^1-3

• bones and joints abnormalities
• chronic pain
• swelling in various parts of the body
• stiffness
• headaches
• problems with swallowing and speaking
• restriction of airways, and breathing difficulties
• hearing impairment or loss

FOP can lead to complications such as pneumonia, thoracic insufficiency syndrome, and heart failure.^1,3

Please speak to your medical team to learn more about the symptoms and complications of FOP.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

FOP is a genetic condition, caused by disease-causing genetic changes (variants) in the ACVR1 gene on chromosome 6.^1,3 ACVR1 gene produces a bone morphogenic protein (activin receptor type IA), important in bone development and repair.^2,3 The genetic variants in ACVR1 gene leads to over-activation of bone formation, causing bones to grow abnormally. The most common genetic variant is the c.617G>A (p.Arg206His) genetic variant, which has been associated with classic FOP. The other genetic variants are known as FOP variants and are often associated with atypical FOP.

In most people, genetic variants in ACVR1 gene occur randomly before birth (de novo) and is not passed down/inherited from their parents.¹ In rare cases, the genetic variant is inherited from an affected parent in an autosomal dominant manner. More information on autosomal dominant inheritance pattern can be found at Centre for Genetics Education: Autosomal dominant inheritance factsheet.

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis of FOP is made based on:¹

• physical examination to look for soft tissue swelling and appearances of abnormal bone formation, and the characteristic malformation of the great toes
• imaging scans to look for bone and joint abnormalities
• genetic testing for disease-causing genetic variants in ACVR1 gene

The Medical Management of Fibrodysplasia Ossificans Progressiva: Current Treatment Considerations includes clinical diagnostic criteria for FOP developed by members of the International Clinical Council on FOP (ICC) and seven consultants from 15 countries. This resource also highlights that precaution during diagnosis procedures (i.e. invasive investigations) are important to prevent injury, which can lead to further abnormal bone formation.

Please speak to your medical team to learn more about the available diagnostic pathways for FOP.

There is currently no curative treatment for FOP. Treatment is targeted at preventing flare-ups and managing symptoms. This may include:^1-3,6

• avoiding potential triggers for flare-ups such as fall prevention, avoid soft tissue injuries, contact sports, and exercise caution during dental and medical care
• an oral medication to prevent formation of HO and enable normal muscle tissue repair. Palovarotene (a specific type of has been approved by the Therapeutic Goods Administration (TGA) for treatment of FOP in Australia. It is available through the Pharmaceutical Benefits Scheme (PBS) through a prescription from a physician with expertise in the management of FOP. information can be found at Services Australia: Fibrodysplasia ossificans progressiva.
• corticosteroid and non-steroidal anti-inflammatory agents (NSAIDs) to reduce inflammation and manage flare-up
• pain management
• use of hearing aids
• management of bone abnormalities such as scoliosis
• occupational therapy assistance with adaptive tools and considerations for physiotherapy. Physiotherapy should be exercised with advice from clinicians with experience working with people living with FOP.

The Medical Management of Fibrodysplasia Ossificans Progressiva: Current Treatment Considerations (also known as The FOP Treatment Guidelines; published in 2024 by the International Clinical Council on FOP) covers recommendations for the management of people living with FOP, special medical considerations, treatment considerations, and emergency guidelines.⁷

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Healthcare professionals involved in the care of people with FOP may include general practitioners (GP), paediatricians, endocrinologist, rheumatologists, occupational therapists, orthodontics (specialised dentists), physiotherapists, genetic counsellors, geneticists, pulmonologists, dermatologists, psychologists.¹ The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

FOP Australia: Health Professionals has information about clinicians with managing FOP in Australia.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

For many rare diseases, palliative care services may be relevant and useful. Palliative care services are available for people (adults, children and their families) living with a life-limiting illness and is not only for end-of-life care. It can also help at any stage of illness from diagnosis onwards, and will look different for different people. Palliative care services provide assistance, support, resources and tools to help people manage their illness and the symptoms, ease pain, and improve comfort and quality of life. If this is relevant to you and you wish to find out more information about palliative care and how it can help you, please visit:

• Australian Institute of Health and Welfare: Palliative care Overview
• Australian Government Department of Health, Disability and Ageing: Palliative care
• Palliative Care Australia

The Medical Management of Fibrodysplasia Ossificans Progressiva: Current Treatment Considerations developed by the International Clinical Council on FOP, published in 2024. It includes recommendations for the management of people living with FOP, special medical considerations, treatment considerations, and emergency guidelines.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

In addition, individuals, their parents, families and carers often develop extensive expertise on their specific rare disease. It is important to recognise that they can contribute valuable knowledge about their rare condition. Rare diseases often impact individuals differently, so it’s important to consider a person’s lived experience.

Below are some considerations for the emergency management of individuals living with FOP, including when presenting to emergency departments:⁷

• Trauma such as bumps, bruises, falls, influenza-like viral illness, as well as those caused by intramuscular immunizations, mandibular blocks for dental work or muscle fatigue can trigger painful flare-ups of FOP, hence caution is recommended
• submandibular swelling in patients who have FOP can be a medical emergency

The Medical Management of Fibrodysplasia Ossificans Progressiva: Current Treatment Considerations covers emergency guidelines for first responders, physicians and dentists, including guidelines regarding intramuscular injections, peripheral/central venous access, and intubation.⁷

FOP Australia: Research has information on research on FOP in Australia and internationally.

International Clinical Council on Fibrodysplasia Ossificans Progressiva (ICCFOP) is an autonomous and independent group of 21 internationally recognized clinical experts in FOP from 14 nations and 5 continents. It was established to consolidate a global voice for the best practices for clinical care and clinical research for people who suffer from FOP.

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries. For more information, please visit the RARE Portal’s Considerations for Participating in Health and Medical Research page.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

It is best to discuss your interest in research, including clinical trials,  with your medical team to determine suitability and eligibility.

Australian Organisation:
FOP Australia
Website: https://fopaustralia.org/
FOP Australia is a volunteer-run registered charity supporting people with FOP in Australia and New Zealand. This work includes supporting the global research effort, improving local clinician access to international expertise, and working with IFOPA.

International Organisation:
International Fibrodysplasia Ossificans Progressiva Association (IFOPA)
Website: https://www.ifopa.org/

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

FOP varies between individuals, and each person’s experience is unique.

FOP Australia: My life with FOP has personal stories of people living with FOP.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

FOP Australia: Support Grant Program has information on financial support to help people living with FOP.

FOP Australia also coordinate the Oliver Collins Education Grant to provide financial support for people with FOP to further their education or learning.

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

People living with a rare disease often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on FOP can be found at:

• FOP Australia: Living with FOP
• International Fibrodysplasia Ossificans Progressiva Association (IFOPA): Patients & Families
• National Organization for Rare Disorders (NORD): Fibrodysplasia Ossificans Progressiva

FOP Australia: Healthcare Professionals

GeneReviews®: Fibrodysplasia Ossificans Progressiva

Online Mendelian Inheritance in Man, OMIM^®:#135100 Fibrodysplasia Ossificans Progressiva; FOP

Orphanet: Fibrodysplasia ossificans progressiva

This page has been co-developed by Rare Voices Australia (RVA)’s RARE Portal team in consultation with FOP Australia.

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.