Bone Abstracts

Introduction: Heterotopic ossification (OH) is a rare condition characterized by the presence of extra-skeletal ossification; in most cases OH is due to the inactivation of the gene of guanine nucleotide-binding protein alpha-stimulating activity polypeptide (GNAS). In some cases they remain confined to skin and subcutaneus tissues (osteoma cutis, Albright hereditary osteodystrophy (AHO), pseudohypoparathyroidism type 1a and c (PHP1a/c), and pseudopseudohypothyroidism (PPHP)), in other they grow also into deep organs (e.g. progressive osseous heteroplasia (POH)).

Case report: We report the case of a 9-year-old boy, who presented soon after birth several cutaneus lesions, increased over time, above all on legs, which were found to be ‘cutanues osteoma’ with a skin biopsy. He was −1/M S.D. for height and M/+1 S.D for weight, he had a small development delay, but no brachydactyly, nor round face and obesity. The genetic analysis showed GNAS mutation (IVS8+2, T>G+ IVS8+26 STOP). Soon before the visit after an incident to his back, he underwent a MRI, showing an aberrant right paravertebral ossification. It was therefore fundamental to understand if the new finding was a sign of a progressive disease, although usually extra-skeletal ossifications in this kind of disorders are not associated with trauma. Physical examination and laboratory determinations permitted to exclude both AHO and PTH resistance. The most specific way to distinguish POH from PHP1a is the study of the genomic imprinting: maternally-inherited GNAS mutations lead to PHP1a, whereas paternally-inherited ones are linked to POH. In our case RNA analysis clarified that the mutation came from the father, confirming the prior suspect of POH. Our child began periodical visits to control the progression of the disease and started a therapy with bisphosphonates, obtaining up to now conflicting effects: we observed no progression of the deep lesions by imaging but our patient’s pain has not improved.

Conclusion: As there is no specific genotype-phenotype correlations between the more progressive forms of HO and the non-progressive ones it is important to follow the patient with appropriate clinical, laboratory and genetic assessments. Besides, the debate on therapy options and results is still open.