National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Progressive osseous heteroplasia


Other Names:
POH; Familial ectopic ossification; Ectopic ossification familial type
Categories:
Progressive osseous heteroplasia (POH) is a progressive bone disorder in which bone forms (ossifies) within skin and muscle tissue.[1] It usually becomes apparent in infancy with skin (cutaneous) ossification, which progresses to involvement of subcutaneous and deep tissues, including muscle.[1][2] In some cases, it first becomes apparent later in childhood or in early adulthood.[1] Ossification may cause pain and open sores (ulcers) in affected areas of the body. Joints may become involved over time, causing impaired mobility.[1] POH is caused by a mutation in the GNAS gene and is inherited in an autosomal dominant manner.[1][2] In most cases, the mutation occurs randomly in a person with no family history of POH. In some cases, the mutation is inherited from a parent.[3] There are currently no effective treatments for POH, and surgery to remove widespread lesions often results in recurrences or complications. However, well-circumscribed lesions can often be removed with successful, long-term results.[2]

POH is thought to be part of a spectrum of related genetic disorders which include Albright hereditary osteodystrophy, pseudohypoparathyroidism, and primary osteoma cutis. These disorders share the features of superficial ossification and being caused by mutations affecting the GNAS gene.[2]
Last updated: 10/24/2016
Symptoms of progressive osseous heteroplasia (POH) usually are apparent within the first few months of life, and may be present from birth. The condition does not affect the formation of any portions of the normal skeleton at birth. Most affected children are diagnosed before the age of ten.[4]

Parents may first notice small rice-sized particles of bone in the skin, causing the skin to feel rough and thick.[4][3] As affected children age, bone formation may progress to subcutaneous tissue and into deeper structures including muscles, tendons and ligaments.[4] It may cause pain and the development of open sores (ulcers) in affected areas of the body.[1] Joints may become involved over time, causing impaired mobility.[1]

As the condition progresses, it may cause restricted mobility of various joints, eventually "locking" the joints (ankylosis). Affected arms and legs may become malformed and may not grow their full length. If bone growth occurs around the spine, scoliosis may develop.[3]

In some individuals, the condition affects a small area of the body; in others, large areas of the body are affected.[4] The rate of progression also varies greatly among affected individuals and is unpredictable.[4] However, most individuals experience a gradual progression of the condition.[3] 
Last updated: 10/24/2016

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.

Showing of 21 |
Medical Terms Other Names
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HPO ID
80%-99% of people have these symptoms
Bone pain 0002653
Ectopic calcification 0010766
Limitation of joint mobility
Decreased joint mobility
Decreased mobility of joints
Limited joint mobility
Limited joint motion
[ more ] 		0001376
Subcutaneous nodule
Firm lump under the skin
Growth of abnormal tissue under the skin
[ more ] 		0001482
30%-79% of people have these symptoms
Ectopic ossification in muscle tissue
Calcification of muscle tissue
0011987
5%-29% of people have these symptoms
Abnormality of the parathyroid gland 0000828
Brachydactyly
Short fingers or toes
0001156
Hypermelanotic macule
Hyperpigmented spots
0001034
Osteoarthritis
Degenerative joint disease
0002758
Papule 0200034
Sarcoma
Cancer of connective tissue
Malignant connective tissue tumor
[ more ] 		0100242
Percent of people who have these symptoms is not available through HPO
Abnormality of the musculature
Muscular abnormality
0003011
Ankylosis 0031013
Autosomal dominant inheritance 0000006
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth
[ more ] 		0001510
Infantile onset
Onset in first year of life
Onset in infancy
[ more ] 		0003593
Juvenile onset
Signs and symptoms begin before 15 years of age
0003621
Osteoma 0100246
Osteoma cutis 0025027
Progressive
Worsens with time
0003676
Variable expressivity 0003828
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Last updated: 7/1/2020
The genetics of progressive osseous heteroplasia (POH) is complex and may not yet be fully understood.[5] It is known to be associated with mutations in the GNAS  gene and has been thought to occur only when a mutation affects the paternally inherited copy of the gene.

The GNAS gene give the body instructions for making parts of protein complexes called G proteins, which trigger signaling pathways that influence the functions of cells. G proteins are believed to play a key role in signaling pathways that regulate bone development (osteogenesis), preventing bone from being produced outside the skeleton. GNAS mutations that cause POH are thought to disrupt G protein function, impairing its ability to regulate osteogenesis. As a result, bone is permitted to grow outside the skeleton, causing the features of POH.[1]
Last updated: 10/24/2016
Progressive osseous heteroplasia (POH) is described as an autosomal dominant trait.[1] This means that having a change (mutation) in only one copy of the responsible gene in each cell is enough to cause features of the condition. In most cases, the mutation occurs randomly (sporadically) for the first time in a person without a family history of POH. While a mutation that causes POH can be inherited, familial cases of POH are extremely rare.[5]

People normally inherit one copy of each gene from each parent. For most genes, both copies are active, or "turned on." For some genes, however, only one of the two copies is active - either the maternal copy or the paternal copy. These differences in activation based on the gene's parent of origin are caused by a phenomenon called genomic imprinting. The gene responsible for POH (the GNAS gene) has a complex genomic imprinting pattern. In some cells the maternal copy is active, while in others the paternal copy is active. Progressive osseous heteroplasia is thought to occur when mutations affect the paternally inherited copy of the gene.[1]

People with POH can conceive and have children.[6] However, because it is an autosomal dominant condition, each child of a person with POH has a 50% chance to inherit the mutation that causes the condition. While POH occurs only when the mutated gene is inherited from the father, Albright's hereditary osteodystrophy (AHO) features can be associated with mutations inherited from either parent, and pseudohypoparathyroidism type 1A and/or AHO-associated obesity can occur when the mutated gene is inherited from the mother.[3]

Due to the complexity of the genetics of POH and related conditions, people with questions about the genetics and inheritance of POH are encouraged to speak with a genetics professional.
Last updated: 10/24/2016
Progressive osseous heteroplasia (POH) must first be differentiated from nonhereditary causes of heterotopic ossification (HO) as well as other hereditary causes. POH is among several related genetic disorders, including Albright hereditary osteodystrophy (AHO), pseudohypoparathyroidism (PHP), and primary osteoma cutis, which share the common features of superficial ossification and association with mutations in the GNAS gene. These disorders are characterized by additional features that are not associated with POH.

POH is diagnosed on the basis of three major criteria:
  • superficial HO that progresses to deep connective tissue;
  • two or fewer AHO features, excluding HO; and
  • no parathyroid hormone (PTH) resistance (as in PHP)

In addition to these key diagnostic criteria, there are several findings that support the diagnosis of POH. These include:

  • a GNAS mutation identified with genetic testing (present in almost two-thirds of POH patients)
  • evidence for paternal inheritance
  • a specific pattern of ossification seen on radiographic imaging
  • a history of intrauterine growth retardation
  • leanness
  • age of onset younger than 1 year[2]
Last updated: 10/24/2016

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.
At this time, there are no effective treatments or prevention for progressive osseous heteroplasia (POH). Surgery to remove diffuse lesions usually leads to recurrences or complications, but areas of well-circumscribed lesions can often be removed, with successful long-term results. Unfortunately, amputations are sometimes needed when there is severe growth retardation and functional ankylosis (locking of joints).[2]

One case report on the use of the bisphosphonate pamidronate in POH suggested stabilization of the condition, but it is unclear how applicable this may be to preventing new skin lesions. Treatment with a bisphosphonate is unlikely to have an effect on preexisting bone formation.[2]

Important conservative approaches include physical therapy to preserve movement, and meticulous skin care to prevent the breakdown of skin.[2] Special shoes, braces, and other devices to assist in walking and weight-bearing have been used to help people with POH involving the lower limbs.[3]
Last updated: 10/25/2016
Because progressive osseous heteroplasia (POH) is so rare, there is limited information about long-term outlook (prognosis).[2] The progression of POH is highly variable even among members of the same family. In some individuals, it may progress extremely slowly; in others it may progress more rapidly. Most individuals experience a gradual progression of the condition.[3] The degree of morbidity depends on the location and extent of abnormal bone formation, and in some cases, the condition results in severe disability. The condition may be associated with restricted movement of the arms and legs caused by "locking" of joints (ankyloses), pain, and secondary osteoporosis.[2] POH may also restrict movement in the hips, jaw, shoulders, and/or other areas of the body.[3] Despite the morbidity associated with POH, there is no known effect on the life span of affected individuals as it does not directly affect the internal organs.[6]
Last updated: 10/24/2016
Progressive osseous heteroplasia (POH) is a very rare condition.[6] A rare disease is a disease or condition affecting fewer than 200,000 persons in the United States. Reportedly, as of 2002, approximately 40 patients had been identified worldwide. It is possible that there are more people with POH who have been misdiagnosed as having other conditions.[6]
Last updated: 10/24/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

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

Social Networking Websites

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

  • Genetics Home Reference (GHR) contains information on Progressive osseous heteroplasia. This website is maintained by the National Library of Medicine.
  • 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

  • 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 Progressive osseous heteroplasia. Click on the link to view a sample search on this topic.

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  • My 17-year-old daughter has progressive osseous heteroplasia and the time has come for me to discuss with her the consequences of this disease in regard to having children of her own. Can you please send be any information you have? See answer


  1. Progressive osseous heteroplasia. Genetics Home Reference. January 2009; http://ghr.nlm.nih.gov/condition/progressive-osseous-heteroplasia.
  2. Pignolo RJ, Ramaswamy G, Fong JT, Shore EM, Kaplan FS. Progressive osseous heteroplasia: diagnosis, treatment, and prognosis. Appl Clin Genet. January, 2015; 8:37-48. https://www.dovepress.com/progressive-osseous-heteroplasia-diagnosis-treatment-and-prognosis-peer-reviewed-fulltext-article-TACG.
  3. Progressive Osseous Heteroplasia. NORD. 2014; https://rarediseases.org/rare-diseases/progressive-osseous-heteroplasia/.
  4. About POH Disease. POHA: Progressive Osseous Heteroplasia Association. http://www.pohdisease.org/ABOUT_POH_DISEASE/.
  5. Happle R. Progressive osseous heteroplasia is not a Mendelian trait but a type 2 segmental manifestation of GNAS inactivation disorders: A hypothesis.. Eur J Med Genet. May, 2016; 59(5):290-294.
  6. Frederick S. Kaplan, Eileen M. Shore, Rachel B. Wagman, Sandra Roth, Fred B. Gardner. What is POH? A Guidebook for Families. POHA: Progressive Osseous Heteroplasia Association. 2002; http://www.pohdisease.org/files/1804/File/pohGuidebook-English.pdf.