Inheritance: sporadic
Gene affected: GNAS1 (encodes the alpha subunit of the G protein, which results in activation of cAMP pathway)
Key features:
(1) polyostotic fibrous dysplasia involving long bones, pelvis, ribs, cranium, facial bones and/or spine
(2) cafe au lait skin pigmentation, with irregular brownish areas over thigh, buttocks, sacrum, upper spine and other sites
(3) endocrine disorder
The skeletal and skin changes may be unilateral.
Endocrine disorders:
(1) precocious puberty in females
(2) hyperthyroidism
(3) hyperparathyroidism
(4) pituitary adenoma (may result in Cushing syndrome, acromegaly, hyperprolactinemia)
Complications:
(1) bone deformity, which may result in facial asymmetry
(2) bone fractures
(3) chondroblastic sarcoma
(4) short adult height (following precocious puberty)
(5) cranial nerve compression with blindness and deafness
(6) life threatening endocrine hyperactivity
(7) cardiac abnormalities, with heart failure and/or cardiac arrhythmias
(8) hepatocellular dysfunction
