Rare Oncology News

Disease Profile

Fibrodysplasia ossificans progressiva

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of onset

Childhood

ageofonset-childhood.svg

ICD-10

M61.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

rnn-autosomaldominant.svg

Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

no.svg

X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

no.svg

X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

no.svg

Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

no.svg

Not applicable

notapplicable.svg

Other names (AKA)

FOP; Myositis ossificans progressiva; Progressive myositis ossificans;

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases; Skin Diseases

Summary

Fibrodysplasia ossificans progressiva (FOP) is a disorder in which skeletal muscle and connective tissue, such as tendons and ligaments, are gradually replaced by bone (ossified). This condition leads to bone formation outside the skeleton (extra-skeletal or heterotopic bone) that restricts movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and moving down the body and into the limbs. People with FOP are born with abnormal big toes (hallux valgus) which can be helpful in making the diagnosis. Trauma, such as a fall or invasive medical procedure, or a viral illness may trigger episodes of muscle swelling and inflammation (myositis). These flareups lasts for several days to months and often result in permanent bone growth in the injured area. FOP is almost always caused by a mutation at the same place in the ACVR1 gene and is inherited in an autosomal dominant manner. This condition occurs in about 1 in 1,600,000 newborns and about 800 people worldwide are known to have FOP.[1][2]

Symptoms

Fibrodysplasia ossificans progressiva (FOP) is characterized by the gradual replacement of muscle tissue and connective tissue (such as tendons and ligaments) by bone, restricting movement. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and proceeding down the body and into the limbs.[1]

The formation of extra-skeletal bone causes progressive loss of mobility as the joints become affected. Speaking and eating may also become difficult as the mouth becomes affected. Over time, people with FOP may become malnourished because of the inability to eat. They may also develop breathing difficulties as a result of extra bone formation around the rib cage that restricts expansion of the lungs.[1]

Any trauma to the muscles of an individual with FOP (a fall or an invasive medical procedure) may trigger episodes of muscle swelling and inflammation followed by more rapid ossification in the injured area. Flare-ups may also be caused by viral illnesses such as the flu.[1]

People with FOP are generally born with malformed big toes. This abnormality of the big toes is a characteristic feature that helps to distinguish this disorder from other bone and muscle problems. Affected individuals may also have short thumbs and other skeletal abnormalities.[1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal vertebral morphology
0003468
Abnormality of the first metatarsal bone
Abnormality of the 1st long bone of foot
0010054
Ectopic ossification in ligament tissue
0011989
Ectopic ossification in muscle tissue
Calcification of muscle tissue
0011987
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion

[ more ]

0001376
Short hallux
Short big toe
0010109
Spinal rigidity
Reduced spine movement
0003306
Subcutaneous nodule
Firm lump under the skin
Growth of abnormal tissue under the skin

[ more ]

0001482
30%-79% of people have these symptoms
Alopecia
Hair loss
0001596
Aplasia/Hypoplasia of the phalanges of the hallux
Absent/small big toe bone
Absent/underdeveloped big toe bone

[ more ]

0010058
Clinodactyly of the 5th finger
Permanent curving of the pinkie finger
0004209
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Respiratory insufficiency
Respiratory impairment
0002093
5%-29% of people have these symptoms
Anemia
Low number of red blood cells or hemoglobin
0001903
Failure to thrive
Faltering weight
Weight faltering

[ more ]

0001508
Glaucoma
0000501
Hallux valgus
Bunion
0001822
Intellectual disability
Mental retardation
Mental deficiency
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Seizure
0001250
Synostosis of joints
Fusion of joints
0100240
1%-4% of people have these symptoms
Basal ganglia calcification
0002135
Intellectual disability, mild
Mental retardation, borderline-mild
Mild and nonprogressive mental retardation
Mild mental retardation

[ more ]

0001256
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Broad femoral neck
0006429
Conductive hearing impairment
Conductive deafness
Conductive hearing loss

[ more ]

0000405
Ectopic ossification in tendon tissue
0011988
Hamartoma
0010566
Metaphyseal widening
Broad wide portion of long bone
0003016
Progressive cervical vertebral spine fusion
0008449
Respiratory failure
0002878
Scoliosis
0002650
Sensorineural hearing impairment
0000407
Short 1st metacarpal
Shortened 1st long bone of hand
0010034
Small cervical vertebral bodies
0004629
Widely spaced teeth
Wide-spaced teeth
Widely-spaced teeth

[ more ]

0000687

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    There is currently no definitive treatment. However, a brief course of high-dose corticosteroids, such as Prednisone, started within the first 24 hours of a flare-up, may help reduce the intense inflammation and tissue swelling seen in the early stages of fibrodysplasia ossificans progressiva. Other medications, such as muscle relaxants, mast cell inhibitors, and aminobisphosphonates, if appropriate, should be closely monitored by a physician. Surgery to remove heterotopic and extra-skeletal bone is risky and can potentially cause painful new bone growth. [3]

    Management Guidelines

    • Emergency Medical Information/Treatment Guidelines
    • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Supporting this Disease

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

        • Support guidebooks published by the International Fibrodysplasia Ossificans Progressiva Association contains information about research and treatment options, as well as articles by parents of affected children and adults with FOP offering insights into the condition.
        • Genetics Home Reference (GHR) contains information on Fibrodysplasia ossificans progressiva. This website is maintained by the National Library of Medicine.
        • The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) support research into the causes, treatment, and prevention of arthritis and musculoskeletal and skin diseases, the training of basic and clinical scientists to carry out this research, and the dissemination of information on research progress in these diseases. Click on the link to view information on this topic.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Fibrodysplasia ossificans progressiva. Click on the link to view a sample search on this topic.

            References

            1. Fibrodysplasia ossificans progressiva. Genetics Home Reference (GHR). August 2007; https://ghr.nlm.nih.gov/condition/fibrodysplasia-ossificans-progressiva.
            2. FOP Fact Sheet. International Fibrodysplasia Ossificans Progressiva Association. https://www.ifopa.org/what-is-fop/overview.html. Accessed 6/5/2014.
            3. Pignolo R, Kaplan F. Pediatric Fibrodysplasia Ossificans Progressiva. E-medicine. July 30, 2009; https://emedicine.medscape.com/article/1007104-overview. Accessed 3/17/2011.

            Rare Oncology News