Late-Onset Progressive Osseous Heteroplasia: 2 Unrelated Cases and Use of Positron Emission Tomography for Diagnosis

Overview

Journal JCEM Case Rep

Specialty Endocrinology

Date 2025 Feb 26

PMID 40008392

Authors

Minh T Pham

John D Mahan

Summit H Shah

Steven I Estes

Stephen G Kaler

Affiliations

Soon will be listed here.

Abstract

Progressive osseous heteroplasia (POH) is a rare autosomal-dominant hereditary bone disorder caused by inactivating pathogenic variants in . POH is characterized by progressive cutaneous ossification and heterotopic ossification in skeletal muscles and subdermal connective tissues. Understanding of the natural history and phenotypic heterogeneity of the illness is incomplete. We report 2 affected male subjects with a milder than usual clinical course, highlight their clinical presentations and molecular correlates, and propose sodium F-fluorine positron emission tomography (PET) scanning as a sensitive technique for POH diagnosis and management.

References

Juppner H, Bastepe M . Different mutations within or upstream of the GNAS locus cause distinct forms of pseudohypoparathyroidism. J Pediatr Endocrinol Metab. 2006; 19 Suppl 2:641-6. DOI: 10.1515/jpem.2006.19.s2.641. View

Han S, Lee Y, Shin C, Yang S, Lim B, Cho T . Clinical and Molecular Characteristics of GNAS Inactivation Disorders Observed in 18 Korean Patients. Exp Clin Endocrinol Diabetes. 2019; 129(2):118-125. DOI: 10.1055/a-1001-3575. View

Suntharesan J, Lyulcheva-Bennett E, Hart R, Pizer B, Hayden J, Ramakrishnan R . Medulloblastoma in a child with osteoma cutis - a rare association due to loss of expression. J Pediatr Endocrinol Metab. 2024; 37(5):467-471. DOI: 10.1515/jpem-2023-0533. View

Pereda A, Martos-Tello J, Garin I, Errea-Dorronsoro J, Perez de Nanclares G . Progressive osseous heteroplasia caused by a mosaic GNAS mutation. Clin Endocrinol (Oxf). 2018; 88(6):993-995. DOI: 10.1111/cen.13584. View

Pignolo R, Ramaswamy G, Fong J, Shore E, Kaplan F . Progressive osseous heteroplasia: diagnosis, treatment, and prognosis. Appl Clin Genet. 2015; 8:37-48. PMC: 4321643. DOI: 10.2147/TACG.S51064. View

Noversa de Sousa R, Tascilar K, Corte G, Atzinger A, Minopoulou I, Ohrndorf S . Metabolic and molecular imaging in inflammatory arthritis. RMD Open. 2024; 10(1). PMC: 10862311. DOI: 10.1136/rmdopen-2023-003880. View

Puri T, Frost M, Moore A, Choudhury A, Vinjamuri S, Mahajan A . Utility of a simplified [F] sodium fluoride PET imaging method to quantify bone metabolic flux for a wide range of clinical applications. Front Endocrinol (Lausanne). 2023; 14:1236881. PMC: 10534005. DOI: 10.3389/fendo.2023.1236881. View

Lin M, Numbenjapon N, Germain-Lee E, Pitukcheewanont P . Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy. J Pediatr Endocrinol Metab. 2015; 28(7-8):911-8. DOI: 10.1515/jpem-2014-0435. View

Seror R, Job-Deslandre C, Kahan A . Progressive osseous heteroplasia: a rare case of late onset. Rheumatology (Oxford). 2007; 46(4):716-7. DOI: 10.1093/rheumatology/kel416. View

10.

Ozaki K, Mituboshi A, Nagai M, Nishiyama A, Nishimura G, Morisada N . Mild progressive osseous heteroplasia overlap syndrome with PTH and TSH resistance appearing during adolescence and not early childhood. Endocrine. 2021; 74(3):685-689. DOI: 10.1007/s12020-021-02821-y. View

11.

Lebrun M, Richard N, Abeguile G, David A, Coeslier Dieux A, Journel H . Progressive osseous heteroplasia: a model for the imprinting effects of GNAS inactivating mutations in humans. J Clin Endocrinol Metab. 2010; 95(6):3028-38. DOI: 10.1210/jc.2009-1451. View

12.

Shore E, Kaplan F . Inherited human diseases of heterotopic bone formation. Nat Rev Rheumatol. 2010; 6(9):518-27. PMC: 3551620. DOI: 10.1038/nrrheum.2010.122. View

13.

Eddy M, Jan de Beur S, Yandow S, McALISTER W, Shore E, Kaplan F . Deficiency of the alpha-subunit of the stimulatory G protein and severe extraskeletal ossification. J Bone Miner Res. 2000; 15(11):2074-83. DOI: 10.1359/jbmr.2000.15.11.2074. View

14.

Ma J, Mo W, Sun J, Li Y, Han T, Mao H . Progressive osseous heteroplasia in a 5-year-old boy with a novel mutation in exon 2 of GNAS: a case presentation and literature review. BMC Musculoskelet Disord. 2023; 24(1):247. PMC: 10064707. DOI: 10.1186/s12891-023-06371-4. View

15.

Shore E, Ahn J, De Beur S, Li M, Xu M, Gardner R . Paternally inherited inactivating mutations of the GNAS1 gene in progressive osseous heteroplasia. N Engl J Med. 2002; 346(2):99-106. DOI: 10.1056/NEJMoa011262. View

16.

Mariani M, Rigante D, Guerriero C, Ricci F, Sani I, Rossodivita A . Progressive osseous heteroplasia in a 7-year-old girl with osteoma cutis and autoimmune thyroiditis: the importance of investigating GNAS mutations. J Eur Acad Dermatol Venereol. 2015; 30(5):905-7. DOI: 10.1111/jdv.13075. View

17.

Goto M, Mabe H, Nishimura G, Katsumata N . Progressive osseous heteroplasia caused by a novel nonsense mutation in the GNAS1 gene. J Pediatr Endocrinol Metab. 2010; 23(3):303-9. DOI: 10.1515/jpem.2010.23.3.303. View