Fibrodysplasia ossificans progressiva

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Fibrodysplasia ossificans progressiva is a disorder in which muscle tissue and connective tissue such as tendons and ligaments are gradually replaced by bone (ossified), forming bone outside the skeleton (extra-skeletal or heterotopic bone) that limits movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and proceeding down the body and into the limbs.

Extra-skeletal bone formation causes progressive loss of mobility as the joints become affected. Inability to fully open the mouth may cause difficulty in speaking and eating. Over time, people with this disorder may experience malnutrition due to their eating problems. They may also have breathing difficulties as a result of extra bone formation around the rib cage that restricts expansion of the lungs.

Any trauma to the muscles of an individual with fibrodysplasia ossificans progressiva, such as a fall or invasive medical procedures, may trigger episodes of muscle swelling and inflammation (myositis) followed by more rapid ossification in the injured area. Flare-ups may also be caused by viral illnesses such as influenza.

People with fibrodysplasia ossificans progressiva are generally born with malformed big toes. This abnormality of the big toes is a characteristic feature that helps to distinguish this disorder from other bone and muscle problems. Affected individuals may also have short thumbs and other skeletal abnormalities.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Variants (also known as mutations) in the ACVR1 gene cause fibrodysplasia ossificans progressiva. This gene provides instructions for making a member of a protein family called bone morphogenetic protein (BMP) type I receptors. The ACVR1 protein is found in many tissues of the body including skeletal muscle and cartilage. It helps to control the growth and development of the bones and muscles, including the gradual replacement of cartilage by bone (ossification) that occurs in normal skeletal maturation from birth to young adulthood.

Studies show that variants in the ACVR1 gene disrupt mechanisms that control the receptor's activity. As a result, the receptor is turned on when it normally should not be. Too much receptor activity causes overgrowth of bone and cartilage, resulting in the signs and symptoms of fibrodysplasia ossificans progressiva.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Most cases of fibrodysplasia ossificans progressiva result from new variants in the gene. These cases occur in people with no history of the disorder in their family. In a small number of cases, an affected person has inherited the variant from one affected parent.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

Fibrodysplasia ossificans progressiva is a very rare disorder, believed to occur in approximately 1 in 1 million people worldwide. Several hundred cases have been reported.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal hallux morphology · Very frequent (99-80%)

This term applies for all abnormalities of the big toe, also called hallux.

Abnormal vertebral morphology · Very frequent (99-80%)

An abnormality of one or more of the vertebrae.

Abnormality of the first metatarsal bone · Very frequent (99-80%)

An anomaly of the first metatarsal bone.

Ectopic ossification · Obligate (100%)

Formation of abnormal, extraskeletal bony tissue, i.e., the presence of bone in soft tissue where bone normally does not exist.

Ectopic ossification in ligament tissue · Very frequent (99-80%)

Formation of abnormal bony tissue within ligament tissue.

Ectopic ossification in muscle tissue · Very frequent (99-80%)

Formation of abnormal bony tissue within muscle tissue.

Fused cervical vertebrae · Very frequent (99-80%)

A congenital anomaly characterized by a joining (fusion) of two or more cervical vertebral bodies with one another.

Limitation of joint mobility · Very frequent (99-80%)

A reduction in the freedom of movement of one or more joints.

Osteochondroma · Very frequent (99-80%)

A cartilage capped bony outgrowth of a long bone. Osteochondroma arises on the external surface of bone containing a marrow cavity that is continuous with that of the underlying bone.

Short hallux · Very frequent (99-80%)

Underdevelopment (hypoplasia) of the big toe.

Spinal rigidity · Very frequent (99-80%)

Reduced ability to move the vertebral column with a resulting limitation of neck and trunk flexion.

Subcutaneous nodule · Very frequent (99-80%)

Slightly elevated lesions on or in the skin with a diameter of over 5 mm.

Abnormal femoral neck morphology · Frequent (79-30%)

An abnormality of the femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).

Abnormal thumb morphology · Frequent (79-30%)

An abnormal structure of the first digit of the hand.

Other findings in the same source

From: Orphanet

Additional reported features include Alopecia (Frequent (79-30%)); Clinodactyly (Frequent (79-30%)); Hearing impairment (Frequent (79-30%)); Hip dysplasia (Frequent (79-30%)); Hip pain (Frequent (79-30%)); Increased susceptibility to fractures (Frequent (79-30%)); Scoliosis (Frequent (79-30%)); Aplasia/Hypoplasia of the phalanges of the hallux (Frequent (79-30%)); Respiratory insufficiency (Frequent (79-30%)); Deep venous thrombosis (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Fibrodysplasia ossificans progressiva is Orthopaedics, with a orthopaedic specialist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• What explains the change in pain, movement or function?
• Which activities need adjustment while the diagnosis is being clarified?
• What are the roles of rehabilitation, observation and surgery in this situation?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Fibrodysplasia ossificans progressiva. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.