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ORPHA:337

Fibrodysplasia ossificans progressiva

low confidenceDisorder

Also known as: FOP · Myositis ossificans progressiva · Stone man syndrome

Publications

5,929

Trials

15

Interventional, condition-specific

Researchers

1,030

Distinct authors in sample

Gene link

ACVR1

Definitive

Readiness

6/6

Stages with a signal

Clinical definition (Orphanet)

Fibrodysplasia ossificans progressiva (FOP) is a severely disabling heritable disorder of connective tissue characterized by malformations of the great toes and heterotopic ossification that forms qualitatively normal bone in characteristic extraskeletal sites.

How rare: <1 / 1 000 000 — fewer than one in a million. In a city the size of Kolkata, that might mean on the order of fifteen people.

Orphanet entry

Cross-references

Joined from Mondo / Orphanet. MeSH labels may enter searches; UMLS / OMIM / NCIT are stored for reference.

Additional Mondo synonyms (4)

Stone Man syndrome · fibrodysplasia ossificans progressiva · fop · progressive myositis ossificans

Research stages

Trial readiness signals

Where this condition sits on an open-data research pipeline — not how close a treatment is, and not medical advice. Empty stages often mean “not in these databases under this Mondo ID,” not “impossible.”

6/6 stages with a signal

An interventional trial matched this condition name on ClinicalTrials.gov — see trials below.

  1. Gene identifiedPresent

    Definitive — ACVR1

  2. LiteraturePresent

    5,929 matched papers (3,859 in last 10 years) Source

  3. Phenotype characterisedPresent

    63 HPO annotations (e.g. Mild intellectual disability; Short hallux; Elevated circulating alkaline phosphatase concentration) Source

  4. Animal modelPresent

    7 genotype models (Mus musculus) Source

  5. Orphan designationPresent

    1 FDA · 7 EMA designations (1 FDA orphan-indication approval) — e.g. palovarotene Source

  6. Interventional trialPresent

    15 matched on ClinicalTrials.gov (2 recruiting in sample)

Biology

Genes and phenotypes

Gene–disease validity from GenCC, plus phenotypes and animal models joined from Monarch Initiative via Mondo ID — not a clinical diagnosis aid.

Do we know what causes it?

Yes — we know a specific gene responsible (ACVR1).

GenCC classification: Definitive.

Phenotypes (Monarch / HPO)

63

Associated phenotypes · MONDO:0007606

  • Mild intellectual disability
  • Short hallux
  • Elevated circulating alkaline phosphatase concentration
  • Ectopic ossification in muscle tissue
  • Ectopic ossification in tendon tissue

Showing 5 of 63 — open Monarch for the full list.

Animal models (Monarch / Alliance)

7

Model associations linked to this Mondo ID

Monarch fetch 2026-07-29

Therapies

Designations, candidates, and chemicals

FDA OOPD and EMA orphan designations, Open Targets clinical candidates, and CTD chemical associations via MyDisease.info. These never change the interventional-trial headline.

Orphan designation (FDA · EMA)

8

Designations · 1 with FDA orphan-indication approval

  • FDA palovarotenefibrodysplasia ossificans progressiva · 2014-07-21 · Not FDA Approved for Orphan Indication
  • EMA zilurgisertibTreatment of fibrodysplasia ossificans progressiva · 22/08/2025 · PositiveEMA designation
  • EMA andecaliximabTreatment of fibrodysplasia ossificans progressiva · 19/02/2024 · PositiveEMA designation
  • EMA human monoclonal antibody against activin ATreatment of fibrodysplasia ossificans progressiva · 18/11/2016 · PositiveEMA designation
  • EMA (R)‑tetrahydrofuran‑3‑yl 4‑(6‑(5‑(4‑ethoxy‑1‑isopropylpiperidin‑4‑yl)pyridin-2-yl)pyrrolo[1,2-b]pyridazin-4-yl)piperazine-1-carboxylate sesquisuccinateTreatment of fibrodysplasia ossificans progressiva · 13/11/2020 · PositiveEMA designation
  • EMA saracatinibTreatment of fibrodysplasia ossificans progressiva · 09/01/2026 · PositiveEMA designation
  • EMA palovarotene (Sohonos)Treatment of fibrodysplasia ossificans progressiva · 19/11/2014 · WithdrawnEMA designation
  • EMA (S)-1-(4-(1-(3,4,5-trimethoxyphenyl)-1H-imidazol-4-ylamino)thieno[2,3-d]pyrimidin-2-yl)pyrrolidine-2-carboxamideTreatment of fibrodysplasia ossificans progressiva · 18/07/2022 · WithdrawnEMA designation

Sources: FDA OOPD · EMA orphan designations

Open Targets candidates

8

Drugs / clinical candidates · MONDO_0007606

CTD chemicals (MyDisease.info)

No CTD chemical associations returned for this Mondo ID.

Literature

Is anyone studying this?

5,929

5,929 papers — among the better-studied rare conditions, though still a fraction of common-disease literature (breast cancer: over 700,000). Median papers in the last 10 years for a rare disease in this dataset (publications denominator n=3967) is 59.

5,929 papers since the earliest indexed year in this search — median last-10-year count for a rare disease in this dataset is 59 (publications denominator n=3967).

3,859 in the last 10 years · low confidence

Phrase hits: 2,692 · MeSH hits: 0

Open Europe PMC search

Who's working on it?

1,030

Distinct author names in 200 sampled papers — named people below.

Who's working on it?

People publishing on this condition (sampled Europe PMC records). Affiliation is the most recent found in that sample.

  1. 01
    Pignolo RJ17 papers · 2026

    Department of Medicine, Mayo Clinic, Rochester, MN, USA.

    Papers in Europe PMC
  2. 02
    Kaplan FS14 papers · 2026

    Departments of Orthopaedic Surgery & Medicine, The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

    Papers in Europe PMC
  3. 03
    Hsiao EC11 papers · 2026

    Division of Endocrinology and Metabolism, the UCSF Metabolic Bone Clinic, the Eli and Edythe Broad Institute for Regeneration Medicine, and the Institute of Human Genetics, Department of Medicine, and the UCSF Program in Craniofacial Biology, University of California-San Francisco, San Francisco, CA, USA.

    Papers in Europe PMC
  4. 04
    Al Mukaddam M9 papers · 2026

    Departments of Orthopaedic Surgery & Medicine, The Center for Research in FOP and Related Disorders, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.

    Papers in Europe PMC
  5. 05
    Eekhoff EMW8 papers · 2025

    Department of Internal Medicine, Endocrinology Section, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands.

    Papers in Europe PMC
  6. 06
    Keen R7 papers · 2026

    Centre for Metabolic Bone Disease, Royal National Orthopaedic Hospital, Stanmore, UK.

    Papers in Europe PMC
  7. 07
    Mishina Y6 papers · 2026

    Department of Biologic and Materials Science, School of Dentistry, University of Michigan, Ann Arbor, MI 48109.

    Papers in Europe PMC
  8. 08
    Shore EM6 papers · 2026

    Department of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 3450 Hamilton Walk, Philadelphia, PA 19104, USA.

    Papers in Europe PMC
  9. 09
    Baujat G5 papers · 2026

    Reference Center for Skeletal Dysplasia, INSERM UMR1163, Imagine Institute, Necker-Enfants Malades Hospital, Paris Cité University, 75015 Paris, France.

    Papers in Europe PMC
  10. 10
    Botman E5 papers · 2025

    Department of Internal Medicine, Endocrinology Section, Amsterdam University Medical Centers, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, Netherlands.

    Papers in Europe PMC

Clinical research

Is a treatment being tested?

15

interventional trials for this specific condition

15 interventional trials matched this specific condition name; 2 currently recruiting in our sample.

Data as of 11 September 2026 · last trial check 28 July 2026

15 interventional trials — more than 77.2% of diseases in the trials denominator have none at all (5501 of 7126; this disease is at the 94th percentile).

low confidence · 94th percentile (trials denominator)

Recruiting interventional trials

From the matched ClinicalTrials.gov set

15 interventional trials matched after quoted-phrase search and title/condition post-filter.

Observational and natural-history studies

7 observational studies match this condition. These do not test a treatment and are not counted in the interventional-trial headline, but they are genuine research: natural-history work often defines the endpoints needed for a future rare-disease trial, and families may be able to enroll.

Recruiting or not-yet-recruiting

Open the complete matched search on ClinicalTrials.gov

Other registries (secondary)

Broader net from EU CTIS, ISRCTN, and ICTRP when available — deduped against ClinicalTrials.gov IDs already counted above. Dual-model LLM relevance gates what we keep. These rows are not added to the interventional headline.

raw 5 · after dedupe 5 · already on CT.gov 0 · kept 0 · parent 0 · uncertain 5 · dropped 0 · fetched 2026-07-29

Source notes: ictrp: Error: ICTRP public search unavailable (WHO portal is SPA-only; SOAP needs partnership). Tried: https://apps.who.int/tri

No secondary-registry studies passed dual-model relevance for this condition name (after dedupe).

Uncertain / not reviewed (5)

Where to find support

Condition-specific patient organisations, when Orphanet lists them, are on the disease’s Orphanet page. We also link umbrella groups that support undiagnosed and ultra-rare families.

Orphanet entry for Fibrodysplasia ossificans progressiva — check Associations / patient organisations on that page.

India — NPRD

Last verified 2026-07-26

This ORPHAcode is not on our curated NPRD list (direct or Mondo-parent match). That does not decide clinical eligibility; families in India should ask a notified Centre of Excellence about current coverage.

Hand-curated for this project. ORPHAcode mappings are best-effort and may be incomplete or imprecise for umbrella categories. Parent (Mondo) matches mean the policy lists a broader category — confirm eligibility with a Centre of Excellence. Financial entitlements summarised from public policy statements and may change. This is not official government guidance.

How we counted this

Europe PMC query (preferred label + any corrected label + Orphanet and Mondo exact synonyms, stoplisted; unioned with resolved MeSH labels when available). UMLS / OMIM / NCIT cross-references are stored on the overview but are not added to the query string.

("Fibrodysplasia ossificans progressiva" OR "Myositis ossificans progressiva" OR "Stone man syndrome" OR "progressive myositis ossificans") OR ("ACVR1" OR "ACVR1 syndrome" OR "ACVR1-related")

Run this search on Europe PMC

ClinicalTrials.gov query (quoted phrases + MeSH via query.cond, plus recall-expansion terms when used):

"Fibrodysplasia ossificans progressiva" OR "Myositis ossificans progressiva" OR "Stone man syndrome" OR "progressive myositis ossificans"

Interventional trials matched via: phrase (mesh = registered under a MeSH descriptor no name phrase would catch; recall-expansion = gene / selected parent terms used only for trials).

Study-type breakdown: 15 interventional · 7 observational · 1 expanded access. Only interventional studies enter the trial headline.

Query health: ok — strategies attempted: phrase; with hits: phrase

Run this search on ClinicalTrials.gov

Synonyms dropped by stoplist: FOP

Confidence reasoning

  • Preferred label is multi-word and distinctive
  • 1 synonym(s) dropped by stoplist (may under-count)
  • No label/synonym collisions with other diseases in this corpus
  • Publication count (5929) is implausibly high for prevalence class "<1 / 1 000 000" — treat as possible over-matching, not a measure of research intensity

Ingested 2026-07-26T13:28:04.807Z