Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

(*) mandatory field


Other search option(s)

Fibrodysplasia ossificans progressiva

Synonym(s) FOP
Myositis ossificans progressiva
Stone man syndrome
Prevalence <1 / 1 000 000
Inheritance Autosomal dominant
or Not applicable
Age of onset Childhood
  • M61.1
  • C0016037
  • D009221
  • 10068715


Disease definition

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


The worldwide prevalence is approximately 1/2,000,000. There is no ethnic, racial, gender, or geographic predilection to FOP.

Clinical description

Children who have FOP appear normal at birth except for congenital malformations of the great toes (hallux valgus, malformed first metatarsal, and/or monophalangism). During the first decade of life, sporadic episodes of painful soft tissue swellings (flare-ups) occur which are often precipitated by soft tissue injury, intramuscular injections, viral infection, muscular stretching, falls or fatigue. If diagnosis of FOP is suspected, any invasive intervention (such as biopsy), which may lead to flare-ups, is contraindicated. These flare-ups transform skeletal muscles, tendons, ligaments, fascia, and aponeuroses into heterotopic bone, rendering movement impossible. Patients with atypical forms of FOP have been described. They either present with the classic features of FOP plus one or more atypical features (e.g. intercurrent aplastic anemia, craniopharyngioma, childhood glaucoma or growth retardation) (FOP plus), or present major variations in one or both of the two classic defining features of FOP (e.g., normal great toes or severe reduction deficits of digits) (FOP variants).


Classic FOP is caused by a recurrent activating mutation (617G>A; R206H) in the gene ACVR1 (ALK2) encoding Activin A receptor type I/Activin-like kinase 2, a bone morphogenetic protein (BMP) type I receptor. Atypical FOP patients also have heterozygous ACVR1 missense mutations in conserved amino acids.

Diagnostic methods

The diagnosis of FOP is made by clinical evaluation. Plain radiographs can substantiate more subtle great toe abnormalities and the presence of heterotopic ossification. Confirmatory genetic testing is available.

Differential diagnosis

Differential diagnosis includes progressive osseous heteroplasia, osteosarcoma, lymphedema, soft tissue sarcoma, desmoid tumors (see these terms), aggressive juvenile fibromatosis, and non-hereditary (acquired) heterotopic ossification.

Antenatal diagnosis

Prenatal testing is not yet routinely available.

Genetic counseling

Although most cases of FOP are sporadic (non-inherited mutations), a small number of inherited FOP cases show germline transmission with an autosomal dominant pattern.

Management and treatment

At present, there is no definitive treatment, but a brief 4-day course of high-dose corticosteroids, started within the first 24 hours of a flare-up, may help reduce the intense inflammation and tissue edema seen in the early stages of the disease. Preventative management is based on prophylactic measures against falls (e.g. improvement in household safety, use of protective headgear), respiratory decline (e.g., incentive spirometry), and viral infections.


The median lifespan is approximately 40 years of age. Most patients are wheelchair-bound by the end of the second decade of life and commonly die of complications of thoracic insufficiency syndrome.

Expert reviewer(s)

  • Dr Kaplan FREDERICK
  • Dr Robert PIGNOLO
  • Dr Eileen SHORE

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.

Captcha image

Detailed information

Summary information
Anesthesia guidelines
Review article
Guidance for genetic testing
Article for general public
Get Acrobat Reader
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.