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 hyperthyroidism, hypercorticism, pituitary gigantism, or
acromegaly. Nonendocrine abnormalities in this disorder include
hypophosphatemia, chronic liver disease, tachycardia, and rarely sudden
death, possibly from cardiac arrhythmias.
Cushing-like habitus and café-au-lait skin pigmentation in a small
girl with McCune-Albright syndrome. Note precocious breast development.
Polyostotic Fibrous Dysplasia; Osteitis Fibrosa Cystica;
McCune Syndrome; Albright Syndrome; Osteitis Fibrosa Disseminata.
Genetic disorder first described in 1936 by Donovan James
McCune, an American pediatrician, and then in 1937 by Fuller Albright, an
Occurs sporadically; more common in females.
Autosomal dominant lethal mosaic postzygotic
somatic mutation in the GNAS 1 gene located on chromosome 20q13.2.
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.
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. Multinodular goiter (M = F) and hyperthyroidism in 20 to 40%
of patients. Pathologic fractures and deformities of long bones resulting
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
Clinical features of endocrine abnormalities,
café-au-lait spots, and polyostotic fibrous dysplasia. Biochemical: Thyroid
(mildly elevated T3, low TSH); adrenal (raised cortisol and low ACTH
levels, adrenal function not suppressed by dexamethasone); pituitary
(elevated growth hormone and prolactin levels); hypophosphatemia as a result
of decreased resorption of phosphate in the renal tubule; ovaries (estradiol
varies from normal to markedly elevated levels, suppressed levels of LH and
FSH, no response to luteinizing hormone-releasing hormone stimulation).
Imaging studies: Ultrasonography (ovarian cysts, nodular adrenal
hyperplasia); skeletal radiography (widespread cystic bony lesions, advanced
bone age, fractures and deformities of long bones, bony lesions in base of
Direct laryngoscopy and ...