Fibrodysplasia Ossificans Progressiva (FOP)
What is FOP?
Fibrodysplasia Ossificans Progressiva (FOP) is an ultra‑rare and disabling genetic disorder affecting approximately 1 in 1 million individuals. It is the only condition known to medicine in which soft tissues—such as muscles, tendons, and ligaments—gradually transform into bone, creating a “second skeleton” that increasingly restricts movement.
Key Symptoms & Early Signs
- Congenital toe anomalies: Nearly all affected infants are born with malformed big toes—shortened, turned under, or missing joints—and about half have thumb anomalies.
- Flare-ups: Painful, warm swellings appear unpredictably or after minor injury/illness, progressing to ossification over weeks to months .
- Restricted movement: Ossification often begins in the neck and shoulders, then spreads downward and outward, leading to loss of joint mobility, jaw function, respiratory complications, and severely limited movement
- Misdiagnosis risk: Flare-ups are frequently mistaken for tumors or fibromatosis—biopsies or surgery not only provide no benefit but may trigger further HO .
Source:https://www.fopfriends.com/diagnosing-fop
Genetics & Diagnosis
- Caused by a point mutation in the ACVR1 (ALK2) gene, leading to abnormal activation of bone growth signalling.
- Though inherited as an autosomal dominant trait, most cases are spontaneous (de novo) .
- Diagnosis relies on congenital toe anomalies and genetic testing—biopsies should be avoided to prevent flare-ups .
Treatment & Management
- No cure exists yet; management focuses on preventing flare-ups and protecting mobility .
- Avoid trauma: No intramuscular injections, surgery, or unnecessary trauma—trauma often triggers ossification.
- Symptom relief: Use corticosteroids and anti-inflammatories during flare-ups to ease symptoms .
- Supportive care—specialist breathing, feeding, mobility, and physiotherapy—is critical for quality of life.
Living with FOP
- Life expectancy averages around 40–56 years; much depends on respiratory care and trauma avoidance .
- Early recognition of toe anomalies is key to avoiding misdiagnosis and harmful interventions
- Multi-disciplinary care: Involvement of metabolic, genetic, respiratory, and rehabilitation specialists is essential.
Support & Research
FOP Friends (UK):
- The only UK‑based charity for FOP, founded in 2012 to fund awareness and research
- Has raised over £1.7 million for research; actively offers community support, events, and signposting .
International FOP Association (IFOPA):
- Provides mentoring, medical binders, and global patient networking.
Research & Clinical Trials:
- Ongoing efforts include Oxford-led work on ACVR1 and trials of palovarotene and other inhibitors targeting heterotopic ossification.
Summary Table
| Aspect | Details |
|---|---|
| Prevalence | ~1 in 1 million; ~900 cases worldwide |
| Genetic Cause | ACVR1 mutation; autosomal dominant or de novo |
| Early Sign | Malformed big toes; early flare-ups |
| Progression | Soft tissue → ossification; neck down; trauma‑triggered flare-ups |
| Treatment | No cure; focus on prevention & symptom relief |
