Progressive osseous heteroplasia

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Alternate names[edit | edit source]

POH; Familial ectopic ossification; Ectopic ossification familial type

Definition[edit | edit source]

Progressive osseous heteroplasia (POH) is a progressive bone disorder in which bone forms (ossifies) within skin and muscle tissue.

Epidemiology[edit | edit source]

Progressive osseous heteroplasia (POH) is a very rare condition. 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.

Cause[edit | edit source]

  • Progressive osseous heteroplasia is caused by a mutation in the GNAS gene.
  • The GNAS gene provides instructions for making one part of a protein complex called a guanine nucleotide-binding protein, or a G protein.
  • In a process called signal transduction, G proteins trigger a complex network of signaling pathways that ultimately influence many cell functions. The protein produced from the GNAS gene is believed to play a key role in signaling pathways that help regulate the development of bone (osteogenesis), preventing bony tissue from being produced outside the skeleton.

Gene mutations[edit | edit source]

  • The GNAS gene mutations that cause progressive osseous heteroplasia disrupt the function of the G protein and impair its ability to regulate osteogenesis.
  • As a result, bony tissue grows outside the skeleton and causes the complications associated with this disorder.

Inheritance[edit | edit source]

Autosomal dominant pattern, a 50/50 chance.
  • This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.
  • People normally inherit one copy of each gene from their mother and one copy from their father.
  • For most genes, both copies are active, or "turned on," in all cells. For a small subset of genes, however, only one of the two copies is active.
  • For some of these genes, only the copy inherited from a person's father (the paternal copy) is active, while for other genes, only the copy inherited from a person's mother (the maternal copy) is active.
  • These differences in gene activation based on the gene's parent of origin are caused by a phenomenon called genomic imprinting.
  • The GNAS gene has a complex genomic imprinting pattern. In some cells of the body the maternal copy of the gene is active, while in others the paternal copy is active.
  • Progressive osseous heteroplasia occurs when mutations affect the paternal copy of the gene.

Onset[edit | edit source]

It usually becomes apparent in infancy with skin (cutaneous) ossification, which progresses to involvement of subcutaneous and deep tissues, including muscle. In some cases, it first becomes apparent later in childhood or in early adulthood.

Signs and symptoms[edit | edit source]

  • The condition does not affect the formation of any portions of the normal skeleton at birth.
  • Parents may first notice small rice-sized particles of bone in the skin, causing the skin to feel rough and thick.
  • As affected children age, bone formation may progress to subcutaneous tissue and into deeper structures including muscles, tendons and ligaments.
  • It may cause pain and the development of open sores (ulcers) in affected areas of the body.
  • Joints may become involved over time, causing impaired mobility.
  • 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.
  • In some individuals, the condition affects a small area of the body; in others, large areas of the body are affected.
  • The rate of progression also varies greatly among affected individuals and is unpredictable.
  • However, most individuals experience a gradual progression of the condition.

Clinical presentation[edit | edit source]

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

  • Bone pain
  • Ectopic calcification
  • Limitation of joint mobility(Decreased joint mobility)
  • Subcutaneous nodule(Firm lump under the skin)

30%-79% of people have these symptoms

  • Ectopic ossification in muscle tissue(Calcification of muscle tissue)

5%-29% of people have these symptoms

Diagnosis[edit | edit source]

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:

Treatment[edit | edit source]

  • 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).
  • 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.
  • Important conservative approaches include physical therapy to preserve movement, and meticulous skin care to prevent the breakdown of skin.
  • 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.

Prognosis[edit | edit source]

  • Because progressive osseous heteroplasia (POH) is so rare, there is limited information about long-term outlook (prognosis).
  • 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.
  • 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. POH may also restrict movement in the hips, jaw, shoulders, and/or other areas of the body.
  • 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.


NIH genetic and rare disease info[edit source]

Progressive osseous heteroplasia is a rare disease.


Progressive osseous heteroplasia Resources

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Contributors: Deepika vegiraju, Dr.T