Disease Directory Fibrodysplasia Ossificans Progressiva
Connective Tissue

Fibrodysplasia Ossificans Progressiva

Also known as: FOP, myositis ossificans progressiva, stone man syndrome

Prevalence

1 in 1,600,000–2,000,000

Onset

Congenital (malformed great toes); progressive heterotopic ossification from early childhood

Type

Genetic — autosomal dominant (almost always de novo)

Gene

ACVR1

About Fibrodysplasia Ossificans Progressiva

Fibrodysplasia ossificans progressiva is an ultra-rare and severely disabling disorder caused by a gain-of-function mutation in ACVR1 (encoding ALK2), a BMP type I receptor, leading to progressive and irreversible heterotopic ossification of skeletal muscle, fascia, tendons, and ligaments. The condition is characterised by episodic inflammatory flares that trigger the formation of ectopic bone, ultimately encasing the skeleton and causing profound loss of mobility. A malformed first toe (hallux valgus or monophalangism) present at birth is a pathognomonic clinical sign that permits early diagnosis before ossification begins.

Common Clinical Features

Bilateral malformed great toes (short, monophasic hallux) present at birth Episodic painful soft-tissue swellings (flares) triggered by trauma, infection, or injection Progressive heterotopic bone formation in muscle and connective tissue Severe restriction of joint mobility — neck, shoulders, hips, spine Ankylosis of the jaw limiting mouth opening Thoracic insufficiency syndrome from chest wall ossification Conductive hearing loss in some patients

Clinical Trial Eligibility Tips

What to know before applying to Fibrodysplasia Ossificans Progressiva trials.

Avoid biopsies, intramuscular injections, or surgical procedures unless absolutely life-threatening — these can trigger catastrophic flare and new bone formation; disclose this history to trial staff immediately.

Baseline whole-body 18F-NaF PET-CT or nuclear bone scan documenting extent of heterotopic ossification is standard for clinical trial enrolment; ensure imaging is current.

Active flare at time of enrolment may be an exclusion criterion — document current flare status, recent flare history, and any corticosteroid use prescribed for flare management.

Patient Resources

Patient Organization

International FOP Association

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Natural History Registry

FOP Registry (IFOPA)

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Orphanet

European reference resource for rare diseases (ORPHA:337)

View on Orphanet ↗

NORD

National Organization for Rare Disorders

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Find recruiting Fibrodysplasia Ossificans Progressiva trials

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