Other Skeletal Diseases Resulting from G Protein DefectsFibrous Dysplasia of Bone and McCune-Albright Syndrome

Abstract

This chapter focuses on fibrous dysplasia (FD) of bone and McCune–Albright Syndrome (MAS), which are caused due to defects in G proteins. FD is a benign focal bone lesion composed of fibrous connective tissue with interspersed spicules of immature woven bone and, occasionally, islands of cartilaginous tissue. The lesions usually expand concentrically from the medullary cavity toward the cortex, which results in thinning of the surrounding cortical bone. These lesions may be asymptomatic but often present with local swelling, pain, deformity, or fracture. Involvement of the craniofacial bones may lead to symptoms of nerve entrapment. In the majority of cases patients present with a single focus of FD, referred to as monostotic fibrous dysplasia (MOFD), whereas a minority of patients have multiple bone lesions, referred to as polyostotic fibrous dysplasia (POFD). Among the patients with POFD, a small number have either pigmented "café-au-lait" lesions on the skin and/or endocrinopathies resulting in autonomous hypersecretion of multiple hormones. This constellation is known as McCune-Albright syndrome (MAS). MAS was first described as a specific syndrome distinct from neurofibromatosis and hyperparathyroidism in the 1930s. The classical clinical triad, which has generally defined the syndrome, is the cooccurrence of sexual precocity, POFD, and areas of skin hyperpigmentation (café-au-lait spots). However, multiple other endocrine abnormalities, including thyroid nodules and hyperthyroidism, adrenal hyperplasia and hypercortisolism, pituitary tumors with acromegaly and hyperprolactinemia and hypophosphatemic tickets or osteomalacia, can also be present. Other nonendocrine abnormalities that are also occasionally present, affect the liver, heart, thymus, spleen, bone marrow, gastrointestinal tract, and the brain.