Originally, the McCune-Albright syndrome (MAS) was defined by the triad of polyostotic fibrous dysplasia of bone (FD), café-au-lait skin pigmentation, and precocious puberty (PP). It was recognized that other endocrinopathies, including hyperthyroidism, growth hormone excess, renal phosphate wasting, with or without rickets in children or osteomalacia in adults, and Cushing syndrome, could be found in association with the original triad. Rarely, other organ systems may be involved (liver, cardiac, parathyroid, pancreas).

MAS is rare, as is fibrous dysplasia (FD). FD can involve a single skeletal site (monostotic FD, MFD), or multiple sites (polyostotic FD, PFD). Very rarely one can find PP in association with café-au-lait skin pigmentation in the absence of FD (1%), but in general, FD seems to be the component of the clinical diagnosis most commonly present. Therefore, a more clinically relevant definition of MAS, broader than the original triad of FD + PP + café-au-lait is: MAS = FD + (at least one of the typical hyperfunctioning endocrinopathies and/or café-au-lait spots), almost any combination is possible.

The disease is caused by mutations in the protein that regulates cell action known as Gsa. It is encoded in the genome by the gene GNAS. The fact that the disease has never been passed from parent to child has led to the notion that the disease is the result of mutations that occur after fertilization, at a point early in the development of the embryo or foetus. The earlier in development the mutation occurs, the greater the disease tissue burden.

Typically, the signs and symptoms of either PP or FD usually account for the initial presentation. In girls with PP, it is usually vaginal bleeding or spotting, accompanied by development of breast tissue, with little or no pubic hair. In boys, it can be bilateral (or unilateral) testicular enlargement with penile enlargement, scrotal skin thickening, body odor, pubic and axiallary hair, and precocious sexual behavior.

FD in the axial skeleton usually presents with a limp and/or pain (sometimes reported by children as being 'tired'), but occasionally a pathologic fracture may be the presenting sign. The x-ray will demonstrate a typical lesion arising in the middle of the bone cavity with a 'ground glass' appearance. Alternatively, FD in the craniofacial bones will usually present as a painless 'lump' or facial asymmetry. The areas most commonly involved are the proximal femora and skull base. In retrospect, café-au-lait spots are the most common but unappreciated 'presenting' sign, usually present at birth or shortly thereafter.

Diagnosis of MAS is established on clinical grounds. X-rays are often sufficient to make the diagnosis of FD. A bone scan involving the use of a radioactive tracer that is taken up by bone is the most sensitive tool for detecting the presence of FD lesions, and are often useful, especially at the initial evaluation, for determining the extent of the disease. FD has a typical appearance on radiographs described as 'ground glass'. In general, in the long bones, these lesions have a 'lytic' appearance. The lesions usually arise in the medullary cavity (middle part of the bone) and expand outward replacing normal bone with the result of thinning of the cortex (outer part of the bone). It is possible for any bone to be involved, but the proximal femur (top part) is the site most commonly involved. The bones are 'soft' and prone to deformation, with the classical lesion being the 'shepherd's crook' deformity of the proximal femur (bowing).

As stated earlier, a clinically based definition of MAS, broader than the original triad of FD + PP + café-au-lait is: MAS = FD + at least one of the typical hyperfunctioning endocrinopathies and/or café-au-lait spots. Almost any combination is possible. Genetic testing is possible, but is not routinely available. Because of the somatic mosaic nature of the disease, a negative result from readily available (but unaffected) tissue, does not exclude the presence of the mutation. Testing on white blood cell DNA is possible, but it is unreliable. In most cases, genetic testing contributes little to diagnosis and not at all to management. In regard to diagnosis, by the time affected tissue has been obtained, the diagnosis can be established by histopathological examination of the affected tissue. And, in regards to management, there is no known genotype/phenotype correlation, so knowledge of the specific mutation does not affect management. For this reason, when the diagnosis of MAS is suspected or established, it is important to be aware of the spectrum of tissues that possibly can be involved, and to screen for involvement. Screening, at a minimum, requires a directed medical history and physical examination, and usually involves specific imaging and biochemical testing.