Originally, the McCune-Albright syndrome (MAS) was defined by the combination of fibrous dysplasia of bone (FD), café-au-lait skin pigmentation, and precocious puberty (PP). Later, it was recognized that other endocrinopathies, could be found in association with the original triad. Rarely, other organ systems may be involved (liver, cardiac, parathyroid, pancreas).
Today we define MAS as two of more of the following: 1. FD, 2. typical café-au-lait skin spots, 3. hyperfunctioning endocrine disease (precocious puberty, hyperthyroidism, growth hormone excess, phosphate wasting, neonatal Cushing syndrome). Any part or combination of these features is possible.
The disease is caused by mutations in a protein that regulates cell action known as Gsa. It is encoded in the genome by the gene GNAS. This mutation occurs sometime during development of a baby while it is still in the mother’s uterus. If the mutation occurs early in development, many tissues may be affected. If it occurs late in development, very few tissues may have the mutation. Because the mutation occurs before birth, MAS is considered a genetic disease. But unlike almost all other diseases it is not hereditary because it cannot exist in sperm or egg cells.
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 and breast tissue, with little or no pubic hair. Boys with MAS are less likely to develop PP than girls, however they may present with testicular enlargement (one or both sides) penile enlargement, scrotal skin thickening, body odor, pubic and axillary hair, and precocious sexual behavior. Hyperthyroidism may present with hyperactivity, increased heart rate, or frequently feeling hot. Children with growth hormone excess typically grow very quickly and cross percentile curves on the growth chart. Of note, both PP and hyperthyroidism may also cause children to grow quickly.
For information about FD please see the About FD section.
The diagnosis of MAS is established on clinical grounds. All patients with suspected FD or MAS should have labs checked for endocrine disease. Patients should also have ultrasounds of the thyroid, ovaries and testes. Endocrine disease usually develops during childhood, and all children with suspected MAS should have their growth and development monitored closely.