Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification

N. S. Adegbite, M. Xu, F. S. Kaplan, E. M. Shore, R. J. Pignolo

Research output: Contribution to journalArticle

100 Scopus citations

Abstract

Progressive osseous heteroplasia (POH) is a rare, disabling disease of heterotopic ossification (HO) that progresses from skin and subcutaneous tissues into deep skeletal muscle. POH occurs in the absence of multiple developmental features of Albright hereditary osteodystrophy (AHO) or hormone resistance, clinical manifestations that are also associated with GNAS inactivation. However, occasional patients with AHO and pseudohypoparathyroidism 1a/c (PHP1a/c; AHO features plus hormone resistance) have also been described who have progressive HO. This study was undertaken to define the diagnostic and mutational spectrum of POH and progressive disorders of HO, and to distinguish them from related disorders in which HO remains confined to the skin and subcutaneous tissues. We reviewed the charts of 111 individuals who had cutaneous and subcutaneous ossification. All patients were assessed for eight characteristics: age of onset of HO, presence and location of HO, depth of HO, type of HO, progression of HO, features of AHO, PTH resistance, and GNAS mutation analysis. We found, based on clinical criteria, that POH and progressive HO syndromes are at the severe end of a phenotypic spectrum of GNAS-inactivating conditions associated with extra-skeletal ossification. While most individuals with superficial or progressive ossification had mutations in GNAS, there were no specific genotype-phenotype correlations that distinguished the more progressive forms of HO (e.g., POH) from the non-progressive forms (osteoma cutis, AHO, and PHP1a/c).

Original languageEnglish (US)
Pages (from-to)1788-1796
Number of pages9
JournalAmerican Journal of Medical Genetics, Part A
Volume146
Issue number14
DOIs
StatePublished - Jul 15 2008

Keywords

  • Albright hereditary osteodystrophy
  • GNAS
  • Heterotopic ossification
  • Osteoma cutis
  • Progressive osseous heteroplasia (POH)
  • Pseudohypoparathyroidism

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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