Multiple miliary osteoma cutis is a distinct disease entity: four case reports and review of the literature
- 17 February 2011
- journal article
- case report
- Published by Wiley in British Journal of Dermatology
- Vol. 164 (3), 544-552
- https://doi.org/10.1111/j.1365-2133.2010.10121.x
Abstract
Multiple miliary osteoma cutis (MMOC) is a rare nodular skin disease characterized by tiny bone nodules which usually form on the facial skin, typically in middle age. The aetiology of this phenomenon is poorly understood. To search for possible bone formation progenitors and to look for a possible association with mutations in the GNAS gene (encoding the G-protein α-stimulatory subunit) and related hormonal parameters in patients with MMOC. We also reviewed the literature and discuss the aetiology and pathogenesis of adult-onset primary osteomas. We report four cases of MMOC. Histological samples were analysed for bone morphogenetic protein (BMP)-2, BMP-4 and oestrogen receptor-α known to be involved in bone formation. Endocrinological laboratory investigations and hand X-rays were performed to exclude a systemic disease. The GNAS gene was sequenced from DNA extracted from peripheral blood in all four patients and from a skin sample in one patient to exclude somatic mutations. Histological analyses revealed intramembranous cutaneous bone formation resembling the findings seen in GNAS gene-based osteoma cutis disorders. However, we did not find any germline or somatic GNAS gene mutations in our patients and all laboratory investigations gave normal results. BMP-2 and -4 were expressed normally in MMOC samples, but oestrogen receptor-α was not expressed. Altogether 47 MMOC cases, 41 female and six male, have been published between 1928 and 2009. Of these cases, 55% had a history of pre-existing acne and only 15% had extrafacial osteomas. MMOC is a rare but distinct disease entity of unknown aetiology. Histologically, the tiny nodular osteomas show intramembranous superficial ossification but the aetiology appears to be different from GNAS-related disorders. The osteomas seem to increase slowly in number after appearing in middle age.Keywords
This publication has 43 references indexed in Scilit:
- Nuclear variants of bone morphogenetic proteinsBMC Cell Biology, 2010
- Endogenous bone morphogenetic proteins mediate 1α, 25‐dihydroxyvitamin D3‐induced expression of osteoblast differentiation markers in human dermal fibroblastsJournal of Orthopaedic Research, 2008
- Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS‐based heterotopic ossificationAmerican Journal of Medical Genetics Part A, 2008
- Cyclic dermal BMP signalling regulates stem cell activation during hair regenerationNature, 2008
- Multiple cutaneous osteomas of the face associated with chronic inflammatory acneJournal of the European Academy of Dermatology and Venereology, 2006
- Reduction in Gs?? Induces Osteogenic Differentiation in Human Mesenchymal Stem CellsClinical Orthopaedics and Related Research, 2005
- Multiple miliare Osteome des GesichtsDie Dermatologie, 2002
- Progressive Osseous HeteroplasiaJournal of Bone and Mineral Research, 2000
- Multiple miliary osteoma cutisJournal of the American Academy of Dermatology, 1991
- Pigmented postacne osteoma cutis in a patient treated with minocycline: Report and review of the literatureJournal of the American Academy of Dermatology, 1991