Gnathodiaphyseal dysplasia: A syndrome of fibro-osseous lesions of jawbones, bone fragility, and long bone bowing

We report an unusual generalized skeletal syndrome characterized by fibro-o sseous lesions of the jawbones with a prominent psammomatoid body component , bone fragility, and bowing(sclerosis of tubular bones. The case fits with the emerging profile of a distinct syndrome with similarities to previousl y reported cases, some with an autosomal dominant inheritance and others sp oradic. We suggest that the syndrome be named gnathodiaphyseal dysplasia. T he patient had been diagnosed previously with polyostotic fibrous dysplasia (PFD) elsewhere, but further clinical evaluation, histopathological study, and mutation analysis excluded this diagnosis. In addition to providing a novel observation of an as yet poorly characterized syndrome, the case illu strates the need for stringent diagnostic criteria for Fl). The jaw lesions showed fibro-osseous features with the histopathological characteristics o f cemento-ossifying fibroma, psammomatoid variant. This case emphasizes tha t the boundaries between genuine GNAS1 mutation-positive FD and other fibro -osseous lesions occurring in the jawbones should be kept sharply defined, contrary to a prevailing tendency in the literature. A detailed pathologica l study revealed previously unreported features of cemento-ossifying fibrom a, including the participation of myofibroblasts and the occurrence of psam momatoid bodies and aberrant mineralization, within the walls of blood vess els. Transplantation of stromal cells grown from the lesion into immunocomp romised mice resulted in a close mimicry of the native lesion, including th e sporadic formation of psammomatoid bodies, suggesting an intrinsic abnorm ality of bone-forming cells.