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  1. M. A. Manning,
  2. A. Kwan
  1. Department of Pediatrics, Stanford University School of Medicine, 1Department of Pathology


Osteoma cutis is the presence of bone formation within the skin in the absence of a preexisting lesion. The bone arises through mesenchymal ossification without cartilage precursors. It is a feature of Albright hereditary osteodystrophy (AHO), fibrodysplasia ossificans progressiva (FOP), platelike osteoma cutis and progressive osseous heteroplasia (POH). Recently, it has been demonstrated that inactivating mutations in GNAS1, the gene for guanine nucleotide binding protein (G protein) alpha stimulating activity polypeptide 1 are responsible for both AHO and POH. The purpose of this report is to present a patient with osteoma cutis and provide genotype/phenotype correlation supporting a diagnosis of POH. We recently evaluated a 14-month old with lesions histologically consistent with osteoma cutis. First noted on the trunk at 1 month of age, the lesions progressed to the hands, arms and legs. Biopsy of an abdominal lesion identified a normal-appearing dermis with ossifications in the mid and deep dermis. There was slight fibrodysplasia of the surrounding stroma as well as vascular ectasia. Endocrinological studies to rule out AHO were within normal limits. GNAS1 mutation analysis revealed a C≥T change at nucleotide 91 in exon 1b, which causes the substitution of a stop codon for glutamine at aa 31 (Q31X). AHO is characterized by MR, short stature, round face, shortened 4th and 5th metacarpals, pseudohypo- parathyroidism and heterotopic ossification that is limited to the skin and superficial tissues. In contrast, the dermal ossification in POH can present at birth, progresses to involve skeletal muscle and deep connective tissue and is often disabling. GNAS1 mutations described in AHO are distributed throughout the gene, the most common being a 4 bp deletion in exon 7. Ten GNAS1 mutations have been reported in POH patients, 2 of which are also seen in AHO. An apparent imprinting effect of the gene has been proposed, as maternal transmission of GNAS1 mutations leads to the complete form of AHO, whereas paternal transmission results in a less severe form of AHO or POH. Given the normal endocrine studies, normal growth and development, lack of characteristic facial features and skeletal abnormalities and early appearance of the dermal ossification, the diagnosis of POH is suspected for our patient. The presence of a GNAS1 mutation serves to support this theory and helps to further extend the genotype/phenotype correlation for this intriguing condition.

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