McCune-Albright Syndrome

At a glance

It is characterized by the triad of polyostotic fibrous dysplasia, café-au-lait skin pigmentation, and autonomous endocrine hyperfunction. The most common form of autonomous endocrine hyperfunction is gonadotropin-independent precocious puberty, but affected individuals also may have hyperparathyroidism, hyperthyroidism Cushing’s disease, hypercorticism, hyperprolactinemia, pituitary gigantism, or acromegaly. Nonendocrine abnormalities in this disorder include chronic liver disease, tachycardia, and rarely sudden death as a result of cardiac arrhythmias.

Synonyms

Polyostotic Fibrous Dysplasia; Osteitis Fibrosa Cystica; McCune Syndrome; Albright Syndrome; Osteitis Fibrosa Disseminata; Precocious Puberty Independent Gonodotropins in Girls.

History

Genetic disorder first described in 1936 by Donovan James McCune, an American pediatrician, and then in 1937 by Fuller Albright, an American physician. The disease made the US headlines in December 2005 when a Haitian teen affected with the disease, Marlie Casseus, underwent a 17-hour surgical procedure to remove a very large bone tumor-like growth from her face.

Incidence

The exact incidence remains unknown. It seems more common in females.

Genetic inheritance

Autosomal dominant lethal mosaic postzygotic somatic mutation in the GNAS 1 gene located on chromosome 20q13.2.

Pathophysiology

Described as a mosaicism for a mutation in the gene encoding the subunit of the G protein stimulating cyclic adenosine monophosphate (cAMP) formation. This results in activation of various cAMP-dependent receptors including adrenocorticotropic hormone (ACTH), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) receptors leading to autonomous and aberrant behavior toward otherwise normal stimuli.

Clinical aspects

Classic triad of endocrine dysfunction, bone lesions, and pigmented skin lesions. Average age of onset is 3 years. Precocious pseudopuberty (F >M); vaginal bleeding may begin as early as age 4 months and secondary sexual characteristics as early as 6 months. Acromegaly (F = M). Cushing Syndrome may occur in early infancy before onset of precocious pseudopuberty and is associated with adrenocortical hyperplasia. The presence of a multinodular goiter (M = F) and hyperthyroidism is reported in 20 to 40% of patients. The associated pathologic fractures and deformities of long bones result from hypophosphatemic osteomalacia. Shepherd crook deformity of the proximal femur is particularly characteristic, and bony lesions in the base of skull may result in cranial nerve compression, blindness, and deafness. Large, patchy cutaneous pigmentation with irregular margins on neck, face, back, and shoulders are found in approximately 90% of children with this syndrome. Both the bony and skin lesions are limited predominantly to one side.

Diagnosis

Clinical features of endocrine abnormalities, café-au-lait spots, ...