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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

Diagnostic algorithm for distinguishing among GNAS-based conditions of heterotopic ossification.Abbreviations: HO, heterotopic ossification; OC, osteoma cutis; POH, progressive osseous heteroplasia; AHO, Albright hereditary dystrophy; HR, hormone resistance; PPHP, pseudopseudo-hypoparathyroidism; PHP, pseudohypoparathyroidism.
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f5-tacg-8-037: Diagnostic algorithm for distinguishing among GNAS-based conditions of heterotopic ossification.Abbreviations: HO, heterotopic ossification; OC, osteoma cutis; POH, progressive osseous heteroplasia; AHO, Albright hereditary dystrophy; HR, hormone resistance; PPHP, pseudopseudo-hypoparathyroidism; PHP, pseudohypoparathyroidism.

Mentions: POH, other disorders associated with inactivating mutations of GNAS, and POH overlap syndromes are distinguished solely by clinical criteria (Figure 5). GNAS-based disorders of HO can be divided into those presenting with stable superficial bony lesions and those in which superficial lesions progress into deep connective tissue. Among the nonprogressive forms are OC, AHO/PPHP, and PHP1a/c. Those without AHO features have OC. Those with AHO features and no hormone resistance have AHO/PPHP, and those with hormone resistance have PHP (Figure 5). The progressive types are POH and the POH-related syndromes. Patients with POH present with superficial HO that progresses to deeper tissues in the absence of multiple other AHO features and without hormone resistance (Figure 5). A small subset of patients has progressive HO with more extensive AHO features (POH/AHO) or with both AHO features and hormone resistance (POH/PHP1a/1c). It is possible that individuals without progressive HO could be too young at the time of initial diagnosis to have yet developed progressive disease. Similarly, individuals with POH could be too young at the time of diagnosis to have yet developed other features of AHO. Nevertheless, POH and progressive HO syndromes can be distinguished from other GNAS-based disorders by one clinical parameter alone: the extension of HO from superficial to deep tissue. GNAS inactivating mutations, either by presence alone or by mutation pattern within GNAS, do not predict a specific disorder, variability of phenotype, or severity of progression within this spectrum.


Progressive osseous heteroplasia: diagnosis, treatment, and prognosis.

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

Diagnostic algorithm for distinguishing among GNAS-based conditions of heterotopic ossification.Abbreviations: HO, heterotopic ossification; OC, osteoma cutis; POH, progressive osseous heteroplasia; AHO, Albright hereditary dystrophy; HR, hormone resistance; PPHP, pseudopseudo-hypoparathyroidism; PHP, pseudohypoparathyroidism.
© Copyright Policy
Related In: Results  -  Collection

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

f5-tacg-8-037: Diagnostic algorithm for distinguishing among GNAS-based conditions of heterotopic ossification.Abbreviations: HO, heterotopic ossification; OC, osteoma cutis; POH, progressive osseous heteroplasia; AHO, Albright hereditary dystrophy; HR, hormone resistance; PPHP, pseudopseudo-hypoparathyroidism; PHP, pseudohypoparathyroidism.
Mentions: POH, other disorders associated with inactivating mutations of GNAS, and POH overlap syndromes are distinguished solely by clinical criteria (Figure 5). GNAS-based disorders of HO can be divided into those presenting with stable superficial bony lesions and those in which superficial lesions progress into deep connective tissue. Among the nonprogressive forms are OC, AHO/PPHP, and PHP1a/c. Those without AHO features have OC. Those with AHO features and no hormone resistance have AHO/PPHP, and those with hormone resistance have PHP (Figure 5). The progressive types are POH and the POH-related syndromes. Patients with POH present with superficial HO that progresses to deeper tissues in the absence of multiple other AHO features and without hormone resistance (Figure 5). A small subset of patients has progressive HO with more extensive AHO features (POH/AHO) or with both AHO features and hormone resistance (POH/PHP1a/1c). It is possible that individuals without progressive HO could be too young at the time of initial diagnosis to have yet developed progressive disease. Similarly, individuals with POH could be too young at the time of diagnosis to have yet developed other features of AHO. Nevertheless, POH and progressive HO syndromes can be distinguished from other GNAS-based disorders by one clinical parameter alone: the extension of HO from superficial to deep tissue. GNAS inactivating mutations, either by presence alone or by mutation pattern within GNAS, do not predict a specific disorder, variability of phenotype, or severity of progression within this spectrum.

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