Diagnosis guide for clinicians
Fibrodysplasia ossificans progressiva (FOP): when to suspect it and what to test
Fibrodysplasia ossificans progressiva is an autosomal dominant ACVR1 disorder marked by congenital great toe malformations and progressive heterotopic ossification in specific anatomic patterns.Source ICC medical guidelines
GeneReviews reports that nearly 90% of patients are first misdiagnosed, and about 2 in 3 undergo unnecessary, potentially dangerous procedures.
Source GeneReviewsInternational Clinical Council guidelines say surgeries, biopsies and intramuscular immunizations should be deferred when FOP is suspected, until the diagnosis is confirmed.
Source ICC medical guidelines- Inheritance
- Autosomal dominant, Not applicable
- Age of onset
- Childhood
- Prevalence
- Under 1 per 1,000,000 point prevalence, Worldwide
- Under 1 per 1,000,000 point prevalence, United States
- Under 1 per 1,000,000 point prevalence, Europe
- Also called
- FOP, Myositis ossificans progressiva, Stone man syndrome
Live from Orphanet (INSERM) via Orphadata, licensed CC BY 4.0, data version 2026-06-23.
Patterns that should prompt a test for Fibrodysplasia ossificans progressiva (FOP)
Each sign below is common on its own, which is why Fibrodysplasia ossificans progressiva (FOP) is missed. Published studies describe these combinations as the picture to act on. Rows are ordered from the highest published figure to the lowest, within each kind of measure.
How often diagnosed patients show it
Share of patients already diagnosed who had the finding, in the group named on each row. Groups differ by age and type, so read each row with its group.
- 1
Short, malformed great toes from birth+Painful soft tissue swellings on the neck, back or scalp+Swelling that hardens into bone
Patients with confirmed FOP in China's national rare disease registry (114) and the French FOP registry (43)
Congenital great toe malformation was reported by 89.5% of 114 Chinese patients (Cui 2026) and found in all 43 French registry cases (Piram 2011).Cui 2026 Chinese national cohort
- 2
Limited neck motion or cervical spine fusion+Malformed great toes+Progressive joint stiffness
Patients with confirmed FOP in China's national registry (114) and a Turkish single-center series (10)
Cervical spine fusion or limited neck motion was reported by 65.8% of 114 Chinese patients (Cui 2026) and seen in 8 of 10 Turkish patients (Acikgoz 2026).Cui 2026 Chinese national cohort
- 3
Neck or back swellings+Malformed great toes+No heterotopic ossification yet on X-ray
7 children aged 3 months to 6 years evaluated before any heterotopic ossification
In 7 children with malformed toes and no ossification yet, 5 had neck or back swellings and all 7 carried the classic ACVR1 variant (Kaplan 2008).Kaplan 2008 early diagnosis report
- 4
Firm, tender scalp nodules in a newborn or infant+Malformed great toes+Nodules that regress on their own
Patients in the French FOP registry (43) and a Turkish single-center series (10)
Scalp nodules were found in 40% of 43 French registry cases, usually as the first sign (Piram 2011), and in 6 of 10 Turkish patients (Acikgoz 2026).Piram 2011 French registry study
- 5
A soft tissue mass labeled as a tumor+Biopsy or excision planned+Malformed great toes not yet noticed
Patients with confirmed FOP in China's national registry (114), and 138 patients in a worldwide survey
A tumor-related label was reported by 36 of 114 Chinese patients, or 31.6% (Cui 2026); cancer was the most common wrong diagnosis worldwide, at 32% (Kitterman 2005).Cui 2026 Chinese national cohort
These figures describe published study groups. They are not the chance that any one patient has Fibrodysplasia ossificans progressiva (FOP), and bars whose ranges overlap are not in a settled order.
Red flags for Fibrodysplasia ossificans progressiva (FOP)
What the cited sources describe, grouped by life stage and organ. Each line links to its source.
Feet and hands from birth
- Short, malformed great toes with hallux valgus, a malformed first metatarsal or a single dysplastic phalanx, present from birth.GeneReviews
- The toe malformation is usually bilateral and often the first clinical feature, seen in more than 97% of patients.GeneReviews
- Prenatal ultrasound may identify the hallux valgus deformity as early as 23 weeks of gestation, according to GeneReviews.GeneReviews
- Thumb malformations occur in about 50%, and finger reduction defects in atypical FOP may be mistaken for brachydactyly.GeneReviews
Swellings and lumps, called flare-ups
- Painful, recurrent soft tissue swellings that may precede ossification, which typically starts near the axial skeleton before reaching the limbs.GeneReviews
- Kitterman and colleagues describe tumor-like swellings on the head, neck, back or shoulders alongside the characteristic short great toes.Kitterman 2005 diagnostic error survey
- Large, firm, tender scalp nodules in newborns and infants were described in 40% of a national registry and generally regress.GeneReviews
- Most children with FOP develop episodic, painful, inflammatory flare-ups during the first decade of life, according to the ICC.ICC medical guidelines
- Ossification with the classic variant begins between ages 1 and 10 years, and may start later in some people with atypical FOP.GeneReviews
After an injury or a procedure
- New swelling or bone after an intramuscular immunization, a mandibular block, blunt muscle trauma, muscle fatigue or an influenza-like illness.ICC medical guidelines
- Explosive, painful new ossification after an attempt to remove heterotopic bone, which the ICC says surgery often provokes.ICC medical guidelines
- Worsening at a biopsy site; in a Chinese national cohort, 41 of 51 patients who had a biopsy reported worsening afterward.Cui 2026 Chinese national cohort
Neck, joints, spine and hearing
- Limited neck motion from cervical spine fusions between C2 and C7, seen in about 80% of patients.GeneReviews
- Progressive loss of joint motion, scoliosis in about 65%, and osteochondromas in about 90%, most often at the proximal medial tibia.GeneReviews
- Conductive hearing loss, present in about 50% of patients and usually beginning in childhood.GeneReviews
- Jaw ossification can impair speaking and swallowing, and chest wall involvement can lead to thoracic insufficiency syndrome.GeneReviews
Family history
- An affected parent is rare, because most people with FOP have the condition from a de novo ACVR1 variant.GeneReviews
- In atypical FOP, a parent's features may go unrecognized, so GeneReviews says a negative family history needs parental testing to confirm.GeneReviews
Fibrodysplasia ossificans progressiva (FOP) is often mistaken for
Diagnoses patients commonly carry first, and why the sources say they are confused.
| First diagnosis | Why it is confused |
|---|---|
| Cancer or sarcoma | Kitterman and colleagues found cancer was the most common incorrect diagnosis, at 32% in their worldwide survey.Kitterman 2005 diagnostic error survey |
| Benign soft tissue tumor such as fibroma or myofibroma | In a Chinese national cohort, 36 of 72 misdiagnosed patients had a tumor-related label, such as fibroma, chondroma, osteochondroma or rhabdomyosarcoma.Cui 2026 Chinese national cohort |
| Desmoid tumor or aggressive juvenile fibromatosis | GeneReviews lists sarcoma, desmoid tumor, aggressive juvenile fibromatosis and lymphedema as causes of tumor-like swellings to consider.GeneReviews |
| Hereditary multiple osteochondromas | Heterotopic bone may be read as osteochondromas when the toes are missed, but hereditary multiple osteochondromas has no hallux malformation or heterotopic ossification.GeneReviews |
| Juvenile bunions or an isolated toe malformation | GeneReviews notes the hallux malformation seen alone may be read as an isolated congenital malformation or as juvenile bunions.GeneReviews |
| Brachydactyly or amniotic band defect | Limb reduction defects with ACVR1 p.Gly328 variants may be misdiagnosed as an amniotic band defect or as brachydactyly type B.GeneReviews |
| Cranial fasciitis | In a French registry review, scalp nodule histology did not help the diagnosis and was read as cranial fasciitis in 2 patients.Piram 2011 French registry study |
| Myositis, lymphadenitis or osteomyelitis | Inflammatory or infectious labels, including myositis, lymphadenitis, fasciitis and osteomyelitis, appeared among misdiagnoses in the Chinese national cohort.Cui 2026 Chinese national cohort |
| Torticollis | Torticollis was among the orthopedic or congenital misdiagnoses that patients reported in the same Chinese national cohort.Cui 2026 Chinese national cohort |
| Progressive osseous heteroplasia | It also forms bone outside the skeleton, but without hallux malformation or inflammatory swellings, and it involves the dermis, which FOP spares.GeneReviews |
| Dental abscess or infection | The ICC notes that an oral or facial swelling of dental origin can be difficult to distinguish from an FOP flare-up.ICC medical guidelines |
Codes patients often carry before this diagnosis
For spotting the pattern in a problem list or registry. Descriptions are checked daily against NLM's ICD-10-CM service; this is not coding advice.
R22.0, R22.1, R22.2Tumor-like swellings on the head, neck, back or shoulders are a hallmark early presentation of FOP.Kitterman 2005 diagnostic error survey
D21.9Tumor-related labels such as fibroma and myofibroma were the most common misdiagnoses in a Chinese national cohort.Cui 2026 Chinese national cohort
D48.110, D48.117GeneReviews lists desmoid tumor among the causes of tumor-like swellings considered before FOP.GeneReviews
Q78.6Heterotopic bone may be misread as the osteochondromas of hereditary multiple osteochondromas, especially when the toes are missed.GeneReviews
Q66.6, M20.10, M20.11, M20.12The great toe malformation alone may be taken for an isolated congenital malformation or for juvenile bunions.GeneReviews
M43.6Torticollis was among the orthopedic misdiagnoses reported in a Chinese national cohort.Cui 2026 Chinese national cohort
Testing for Fibrodysplasia ossificans progressiva (FOP), step by step
The testing order the cited guidance describes, by who it applies to. It summarizes published guidance and is not a plan for any one patient.
Anyone with unexplained swelling, heterotopic ossification or restricted movement
- Look at the feet first
Cui and colleagues propose examining the great toes and thumbs before any invasive procedure, in a pathway that still needs prospective evaluation.Cui 2026 Chinese national cohort
- Toe and lesion radiographs
GeneReviews describes short, malformed first metatarsals and a single dysplastic phalanx on toe films. Radiographs of affected areas demonstrate heterotopic ossification, the bone that forms outside the skeleton.GeneReviews
Anyone with suspected FOP
- Defer invasive procedures
The ICC says elective surgeries, biopsies and intramuscular immunizations should be deferred until a definitive diagnosis is confirmed.ICC medical guidelines
- Clinical diagnosis, genetic confirmation
The ICC calls the diagnosis clinical, based on malformed great toes and progressive heterotopic ossification. It says the diagnosis requires genetic confirmation of a pathogenic ACVR1 variant.ICC medical guidelines
Patients with suggestive findings
- ACVR1 sequence analysis
GeneReviews lists ACVR1 sequencing for c.617G>A, found in more than 97% of patients, and other missense variants. Deletion/duplication testing is not indicated when FOP is strongly suspected.GeneReviews
- Skeletal dysplasia panel
GeneReviews says a skeletal dysplasia panel that includes ACVR1 may be considered, since it limits uncertain findings in genes unrelated to the phenotype.GeneReviews
Infants and young children with malformed great toes
- Testing before any ossification
Kaplan and colleagues confirmed the classic ACVR1 variant in 7 children aged 3 months to 6 years before any heterotopic ossification appeared.Kaplan 2008 early diagnosis report
Atypical features, or no hallux malformation
- Exome or genome sequencing
GeneReviews names comprehensive genomic testing, most often exome sequencing, when FOP was not considered or the great toes look normal.GeneReviews
Anyone with an ACVR1 variant of uncertain significance
- Variant of uncertain significance
GeneReviews says a heterozygous ACVR1 variant of uncertain significance neither establishes nor rules out the diagnosis.GeneReviews
Anyone with suspected or confirmed FOP
- Blood draws
The ICC says patients tolerate gentle venipuncture by an experienced phlebotomist with minimal tourniquet time. It says arterial punctures, central lines and PICC lines may cause ossification.ICC medical guidelines
- Oral or facial swelling
The ICC advises a complete dental examination, because a swelling of dental origin and an FOP flare-up can be hard to tell apart.ICC medical guidelines
Where testing goes wrong
- GeneReviews says biopsies of lesions are never indicated in FOP, because they are likely to cause heterotopic ossification.GeneReviews
- In the Chinese national cohort, 41 of 51 patients reported worsening after biopsy, and 22 of 25 reported recurrence or new lesions after excision.Cui 2026 Chinese national cohort
- Early lesions can be highly cellular on histology and may be mistaken for a neoplastic process, according to Cui and colleagues.Cui 2026 Chinese national cohort
- Kitterman and colleagues found 67% of patients had unnecessary biopsies, and 49% reported permanent loss of mobility from invasive interventions.Kitterman 2005 diagnostic error survey
- The ICC says to avoid intramuscular immunizations and live intranasal influenza vaccines, since they may precipitate flare-ups.ICC medical guidelines
- Mandibular blocks and overstretching of the jaw can trigger flare-ups, and the ICC says to consult FOP dental experts before any procedure.ICC medical guidelines
- Open reduction and internal fixation of a fracture can lead to rapid ossification, and GeneReviews says it is not recommended.GeneReviews
- Normal-looking toes do not exclude atypical FOP, since the hallux malformation can be unilateral or absent in a minority.GeneReviews
- Scalp swellings in young children are early flare-ups, according to the ICC, and they often regress on their own.ICC medical guidelines
- Only 8% of 184 textbooks reviewed by Kitterman and colleagues described FOP adequately, including the warning that trauma accelerates ossification.Kitterman 2005 diagnostic error survey
- Orphanet maps FOP exactly to ICD-10 M61.1 and lists myositis ossificans progressiva among its synonyms.Orphanet cross-references
Where to test
- NIH Genetic Testing Registry: fibrodysplasia ossificans progressiva: Lists clinical ACVR1 sequencing tests and skeletal or connective tissue panels submitted by laboratories. NIH does not independently verify submissions or endorse any laboratory.NIH GTR
Family screening and referral
Who else in the family
- Most people with FOP have a de novo ACVR1 variant, and only rarely does a person with FOP have an affected parent.GeneReviews
- If a parent is affected or carries the variant, each sibling has a 50% risk, and penetrance is estimated to be near complete.GeneReviews
- Each child of a person with FOP has a 50% chance of inheriting the variant and is expected to develop features.GeneReviews
- GeneReviews says it may be appropriate to clarify the status of young siblings to protect them from intramuscular injections and other trauma.GeneReviews
- For adult relatives of a person with classic FOP, genetic testing is not usually required when examination shows no toe deformity and no heterotopic ossification.GeneReviews
- For relatives of a person with atypical FOP, GeneReviews recommends genetic testing, because features may not be apparent on examination.GeneReviews
- Germline mosaicism has been reported, so siblings remain at slightly increased risk even when neither parent's blood shows the variant.GeneReviews
- Prenatal and preimplantation genetic testing are possible once the family ACVR1 variant has been identified.GeneReviews
Who to refer to
- The ICC says each patient should have a primary physician willing to consult an FOP expert and coordinate a local care team.ICC medical guidelines
- Families should hear about the International Clinical Council on FOP, the International FOP Association and national support groups at diagnosis, per the ICC.ICC medical guidelines
- An expert anesthesiologist experienced with FOP must be consulted before any general anesthesia, according to the ICC.ICC medical guidelines
- GeneReviews recommends consultation with a clinical geneticist or genetic counselor after the diagnosis is made.GeneReviews
- Cui and colleagues propose referral to an experienced FOP or rare bone disease center once FOP is suspected.Cui 2026 Chinese national cohort
- In China, orthopedics and pediatrics were the most common first contacts, while rheumatology and endocrinology most often made the diagnosis.Cui 2026 Chinese national cohort
Find a specialist by state
From the CMS NPI Registry, a public directory of US clinicians by registered specialty. A listing is not an endorsement and says nothing about experience with Fibrodysplasia ossificans progressiva (FOP); patient organizations and academic centers can often name experienced clinicians.
ICD-10-CM codes for Fibrodysplasia ossificans progressiva (FOP)
For orders, referrals and prior authorization. Each code is checked daily against NLM's ICD-10-CM service.
Once the diagnosis is confirmed
For the patient: why your doctor ordered this test
Plain language a patient can read or take home.
Your doctor ordered this test because the toes and the lumps or swellings you or your child have can be a sign of FOP.
FOP is a very rare condition that makes bone form in muscles and other soft tissues. It usually starts with a new gene change, and it can also run in families.
The test is a gene test that looks for a change in a gene called ACVR1.
Until the result is back, the FOP experts' guidelines say to put off biopsies, planned surgery and shots given into the muscle. These can make new bone grow.
A gentle blood draw from a vein is usually fine, according to the same guidelines.
If the test confirms FOP, your doctor can connect you with FOP experts and support groups for families.
Questions clinicians ask about Fibrodysplasia ossificans progressiva (FOP) testing
Which combinations of findings should prompt testing for fibrodysplasia ossificans progressiva (FOP)?
Among patients already diagnosed, the most common combination began with short, malformed great toes from birth, seen in 89.5% to 100% of patients with confirmed FOP in China's national rare disease registry (114) and the French FOP registry (43). These figures describe study groups, not any one patient's chance of having fibrodysplasia ossificans progressiva (FOP).
What test confirms fibrodysplasia ossificans progressiva?
A pathogenic ACVR1 variant confirms it, according to International Clinical Council guidelines published in JBMR Plus in 2025, which call the diagnosis clinical but requiring genetic confirmation. GeneReviews (revised May 23, 2024) lists ACVR1 sequence analysis, which finds c.617G>A in more than 97% of patients.
Should a soft tissue mass be biopsied if FOP is possible?
No; the ICC says biopsies, elective surgery and intramuscular immunizations should be deferred until the diagnosis is confirmed. GeneReviews says biopsies of lesions are never indicated, because they are likely to cause heterotopic ossification. In a 2026 Chinese national cohort, 41 of 51 patients who had a biopsy reported worsening afterward.
What is the earliest clinical sign of FOP?
Malformed great toes present at birth are often the first clinical feature, seen in more than 97% of patients, according to GeneReviews. Kaplan and colleagues confirmed FOP genetically in 7 young children with the toe malformation before any heterotopic ossification appeared.
How often is FOP misdiagnosed?
In a 2005 survey of 138 patients, 87% were first given an incorrect diagnosis, most often cancer, and the mean delay to diagnosis was 4.1 years. A 2026 Chinese registry study found 63.2% reported a misdiagnosis, and FOP was not considered at the first visit in 74.6%.
Is drawing blood safe in suspected FOP?
The ICC says patients tolerate peripheral blood collection and IV access when an experienced phlebotomist works gently with minimal tourniquet time. It says arterial punctures, central lines and PICC lines may cause heterotopic ossification and should be avoided unless critical.
What is the ICD-10 code for fibrodysplasia ossificans progressiva?
ICD-10-CM codes it under M61.1, myositis ossificans progressiva, including M61.10 for an unspecified site and M61.19 for multiple sites, per NLM's lookup checked November 10, 2026. Site-specific codes run from M61.111 to M61.179, and Orphanet maps FOP exactly to ICD-10 M61.1.
Sources
- Medical guidelines for fibrodysplasia ossificans progressiva. JBMR Plus 2025;9(11):ziaf150 (Kaplan FS, Pignolo RJ et al for the International Clinical Council on FOP; no funding received; many authors are trial investigators for Incyte, Ipsen or Regeneron), via PubMed Central, 2025-09-19.
- Fibrodysplasia Ossificans Progressiva. GeneReviews, University of Washington, Seattle, via NCBI Bookshelf (NBK558090); Akesson LS, Savarirayan R, 2024-05-23.
- Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva. Pediatrics 2005;116(5):e654-e661 (Kitterman JA, Kantanie S, Rocke DM, Kaplan FS), via PubMed abstract; funding and disclosures not seen, 2005-11.
- The diagnostic journey of fibrodysplasia ossificans progressiva: evidence from a national cohort of 114 patients. Frontiers in Endocrinology 2026;17:1941326 (Cui L, Ouyang Q et al; funded by Beijing and Chinese national science programs; no commercial conflicts declared), via PubMed Central, 2026-10-14.
- Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics 2008;121(5):e1295-e1300 (Kaplan FS et al), via PubMed abstract; funding and disclosures not seen, 2008-05.
- Scalp nodules as a presenting sign of fibrodysplasia ossificans progressiva: a register-based study. Journal of the American Academy of Dermatology 2011;64(1):97-101 (Piram M et al), via PubMed abstract; funding and disclosures not seen, 2011-01.
- Fibrodysplasia ossificans progressiva, ORPHA:337, rare disease cross-referencing (Orphadata API). Orphanet, INSERM, via Orphadata, CC BY 4.0, 2026-06-23.
- Progressive myositis ossificans, also called fibrodysplasia ossificans progressiva (GTR condition record, MedGen C0016037). National Center for Biotechnology Information, NIH, 2026-11-10.
- ICD-10-CM search results for "myositis ossificans progressiva" (Clinical Table Search Service). National Library of Medicine, 2026-11-10.
- Fibrodysplasia ossificans progressiva in children: diagnostic pitfalls and ACVR1 genotype-phenotype spectrum. European Journal of Pediatrics 2026;185(5):335 (Acikgoz NB, Simsek Kiper PO et al; no competing interests declared), via PubMed abstract, 2026-05-02.
A reference for licensed professionals, checked against its sources on November 10, 2026. It summarizes what the cited guidance says and does not tell anyone how to diagnose or treat a specific patient. Guidelines change; the current guideline and the treating clinician's judgment govern. Trial Friend is an independent information service, not a medical provider.