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Progressive osseous heteroplasia: diagnosis, treatment, and prognosis.

Pignolo RJ, Ramaswamy G, Fong JT, Shore EM, Kaplan FS - Appl Clin Genet (2015)

Bottom Line: Progressive osseous heteroplasia (POH) is an ultrarare genetic condition of progressive ectopic ossification.Most cases of POH are caused by heterozygous inactivating mutations of GNAS, the gene encoding the alpha subunit of the G-stimulatory protein of adenylyl cyclase.POH is part of a spectrum of related genetic disorders, including Albright hereditary osteodystrophy, pseudohypoparathyroidism, and primary osteoma cutis, that share common features of superficial ossification and association with inactivating mutations of GNAS.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA ; Department of Orthopaedic Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA ; The Center for Research in FOP and Related Disorders, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

ABSTRACT
Progressive osseous heteroplasia (POH) is an ultrarare genetic condition of progressive ectopic ossification. Most cases of POH are caused by heterozygous inactivating mutations of GNAS, the gene encoding the alpha subunit of the G-stimulatory protein of adenylyl cyclase. POH is part of a spectrum of related genetic disorders, including Albright hereditary osteodystrophy, pseudohypoparathyroidism, and primary osteoma cutis, that share common features of superficial ossification and association with inactivating mutations of GNAS. The genetics, diagnostic criteria, supporting clinical features, current management, and prognosis of POH are reviewed here, and emerging therapeutic strategies are discussed.

No MeSH data available.


Related in: MedlinePlus

Appearance of heterotopic ossification in POH.Notes: (A and B) Early clinical appearance of heterotopic ossification in POH. Note the maculopapular lesions that correspond to extensive dermal and subcutaneous ossification. (C) Advanced heterotopic ossification in POH results in large coalesced bony plaques. Note the distinct lateralization of lesions that is observed in some patients, as well as contracture and ankyloses of the left lower extremity.Abbreviation: POH, progressive osseous heteroplasia.
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f2-tacg-8-037: Appearance of heterotopic ossification in POH.Notes: (A and B) Early clinical appearance of heterotopic ossification in POH. Note the maculopapular lesions that correspond to extensive dermal and subcutaneous ossification. (C) Advanced heterotopic ossification in POH results in large coalesced bony plaques. Note the distinct lateralization of lesions that is observed in some patients, as well as contracture and ankyloses of the left lower extremity.Abbreviation: POH, progressive osseous heteroplasia.

Mentions: 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 PTH resistance (Table 3). Dermal involvement appears as hard maculopapular lesions (Figure 2A and B). Over time, these lesions coalesce into plaques with spread into deeper connective tissues including fascia, skeletal muscle, tendon, and ligament (Figure 2C). Small spicules of dermal bone may occasionally extrude through the epidermis, although bone formation does not originate in the epidermis. Extensive ossification of the deep connective tissues can result in ankylosis of affected joints and growth retardation of involved limbs (Figure 2C).1,87–90 In addition to HO, some patients exhibit one or two AHO features, but never obesity or multiple AHO features.6 Hormonal abnormalities are rarely associated with POH, and never PTH resistance.6


Progressive osseous heteroplasia: diagnosis, treatment, and prognosis.

Pignolo RJ, Ramaswamy G, Fong JT, Shore EM, Kaplan FS - Appl Clin Genet (2015)

Appearance of heterotopic ossification in POH.Notes: (A and B) Early clinical appearance of heterotopic ossification in POH. Note the maculopapular lesions that correspond to extensive dermal and subcutaneous ossification. (C) Advanced heterotopic ossification in POH results in large coalesced bony plaques. Note the distinct lateralization of lesions that is observed in some patients, as well as contracture and ankyloses of the left lower extremity.Abbreviation: POH, progressive osseous heteroplasia.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4321643&req=5

f2-tacg-8-037: Appearance of heterotopic ossification in POH.Notes: (A and B) Early clinical appearance of heterotopic ossification in POH. Note the maculopapular lesions that correspond to extensive dermal and subcutaneous ossification. (C) Advanced heterotopic ossification in POH results in large coalesced bony plaques. Note the distinct lateralization of lesions that is observed in some patients, as well as contracture and ankyloses of the left lower extremity.Abbreviation: POH, progressive osseous heteroplasia.
Mentions: 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 PTH resistance (Table 3). Dermal involvement appears as hard maculopapular lesions (Figure 2A and B). Over time, these lesions coalesce into plaques with spread into deeper connective tissues including fascia, skeletal muscle, tendon, and ligament (Figure 2C). Small spicules of dermal bone may occasionally extrude through the epidermis, although bone formation does not originate in the epidermis. Extensive ossification of the deep connective tissues can result in ankylosis of affected joints and growth retardation of involved limbs (Figure 2C).1,87–90 In addition to HO, some patients exhibit one or two AHO features, but never obesity or multiple AHO features.6 Hormonal abnormalities are rarely associated with POH, and never PTH resistance.6

Bottom Line: Progressive osseous heteroplasia (POH) is an ultrarare genetic condition of progressive ectopic ossification.Most cases of POH are caused by heterozygous inactivating mutations of GNAS, the gene encoding the alpha subunit of the G-stimulatory protein of adenylyl cyclase.POH is part of a spectrum of related genetic disorders, including Albright hereditary osteodystrophy, pseudohypoparathyroidism, and primary osteoma cutis, that share common features of superficial ossification and association with inactivating mutations of GNAS.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA ; Department of Orthopaedic Surgery, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA ; The Center for Research in FOP and Related Disorders, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.

ABSTRACT
Progressive osseous heteroplasia (POH) is an ultrarare genetic condition of progressive ectopic ossification. Most cases of POH are caused by heterozygous inactivating mutations of GNAS, the gene encoding the alpha subunit of the G-stimulatory protein of adenylyl cyclase. POH is part of a spectrum of related genetic disorders, including Albright hereditary osteodystrophy, pseudohypoparathyroidism, and primary osteoma cutis, that share common features of superficial ossification and association with inactivating mutations of GNAS. The genetics, diagnostic criteria, supporting clinical features, current management, and prognosis of POH are reviewed here, and emerging therapeutic strategies are discussed.

No MeSH data available.


Related in: MedlinePlus