McCune–Albright syndrome is a complex genetic disorder affecting the bone, skin, and endocrine systems. It is a mosaic disease arising from somatic activating mutations in "GNAS", which encodes the alpha-subunit of the Gs G-coupled protein receptor. These mutations lead to constitutive receptor activation.
It was first described in 1937 by Donovan James McCune and Fuller Albright.
Signs and symptoms
McCune–Albright syndrome is suspected when two or more of the following features are present:
- Hyperfunctioning endocrine disease (gonadotropin independent precocious puberty, hyperthyroidism, growth hormone excess, neonatal Cushing syndrome)
- Fibrous dysplasia
- Café au lait macules
Patients may have one or many of these features, which may occur in any combination.
The clinical presentation varies greatly depending on the disease features. Patients with fibrous dysplasia may have bone fractures, pain, and deformities.
Cafe-au-lait skin macules tend to have characteristic features, including jagged "coast of Maine" borders, and location respecting the midline of the body.
Endocrine disease in McCune–Albright syndrome results from increased hormone production. The most common endocrinopathy is precocious puberty, which presents in girls with recurrent estrogen-producing cysts leading to episodic breast development, growth acceleration, and vaginal bleeding. Precocious puberty may also occur in boys with McCune–Albright syndrome, but is much less common. Additional potential endocrinopathies include hyperthyroidism and growth hormone excess. Cushing syndrome is a very rare feature that develops only in infancy. Patients with polyostotic fibrous dysplasia may develop low blood phosphate levels due to overproduction of the hormone fibroblast growth factor-23.
McCune–Albright syndrome has different levels of severity. For example, one child with McCune–Albright syndrome may be entirely healthy, with no outward evidence of bone or endocrine problems, enter puberty at close to the normal age, and have no unusual skin pigmentation. Diagnosis may be made only after decades. In other cases, children are diagnosed in early infancy, show obvious bone disease, and obvious increased endocrine secretions from several glands.
Genetically, there is a postzygotic mutation (spontaneous mutation) of the gene GNAS, on the long (q) arm of chromosome 20 at position 13.3, which is involved in G-protein signaling. This mutation, which occurs only in the mosaic state, leads to constitutive receptor signaling and inappropriate production of excess cAMP.
The mutation that causes McCune–Albright syndrome arises very early during embryogenesis. It is not passed down from parent to child. There are no known risk factors for acquiring McCune–Albright syndrome, and no exposures during pregnancy that are known to either cause or prevent the mutation from occurring.
Lauren Ruotolo is an author and involved in advocacy for McCune–Albright syndrome
Mauricio Saravia is an artist and graphic designer