ESPE Abstracts

Background: Fibrous dysplasia (FD) is rare disease that affects skeletal system characterized mostly by abnormal bone formation. The newly formed disorganized mass includes fibrous tissue with poorly organized immature trabeculae. FD is a highly incapacitating condition where fractures, deformities and consecutive functional impairment could occur as mono, olygo or polyostotic form. Aside from predominantly asymmetric skeletal involvement, extra-skeletal manifestations could appear as well. Postzygotic somatic mutation of GNAS1 gene early in embryogenesis is responsible for the disease; however, only in some cases the mutation was detected due to the variable degree of tissue mosaicism. Activating mutation of GNAS1 gene that encodes Ga subunit of G protein, leads to overexpression of adenylyl cyclase and disorganized fibrous development.

Case Report: We present two unrelated male patients with FD with variable presentation of the disease. The first sign of the disease in the first patient was neonatal conjugated hyperbilirubinemia and hepatomegaly, associated with elevated transaminases and hepatic biopsy showing hepatocyte necrosis, consecutive inflammation and bile cholestasis. During the neonatal period, a huge hyperpigmentation was noticed along the right side of the body (arm, leg, thorax). Hepatic dysfunction resolved spontaneously. The second child showed calvarial tumefaction in infancy, mainly on supraorbital region. The initial diferential diagnosis of osteosarcoma was excluded by biopsy that showed cystic fibrotic lesions. Fibrotic tissue expanded along all bones on the skull and made significant pressure on the brain tissue. Both children experienced multiple fractures of the long bones, predominantly femur and humerus starting early in infancy. Irregular ossification was noticed along skeletal system, both with roentgen graph and scintigraphy. Bone biopsy during operation was performed in both, showing abundance of fibrotic cystic lesions and small patches of immature bone. The mutation of GNAS1 gene was found only in the second patient. Growth disorders, precocious puberty or any other endocrine dysfunction were not present in both patients.

Discussion and conclusion: Clinical presentation of FD mostly include trias of symptoms –endocrine dysfunctions, mostly precocious puberty, hyperpigmentation and fractures. Unusual manifestations occur depending on the affected cell lineage during embryogenesis. Therefore, a spectrum of non-endocrine clinical signs of almost every organ and tissue emerge and have to be considered as a part of the disease. Since there are no specific markers for the disease, clinical assessment is critical for establishing the diagnosis, even in patients without hormone disturbances.