Last updated 2mo ago
A 6-year-old girl has precocious puberty with breast development and vaginal bleeding. She has large café-au-lait macules with irregular "coast of Maine" borders and fibrous dysplasia of the femur.
Somatic mosaic; GNAS (Gsα activating mutation)
- NOT inherited (lethal if germline)
- Polyostotic fibrous dysplasia (bone replaced by fibrous tissue)
- Café-au-lait macules with irregular "coast of Maine" borders
- Endocrine hyperfunction: Precocious puberty (GnRH-independent), hyperthyroidism, Cushing syndrome
- Clinical diagnosis based on two or more features of the triad (fibrous dysplasia, café-au-lait macules, autonomous endocrine hyperfunction)
- Molecular confirmation requires testing affected tissue (bone lesion, affected skin) for the mosaic GNAS variant; peripheral blood is often negative
- Skeletal survey or technetium bone scan to map polyostotic fibrous dysplasia; endocrine workup for the relevant axis
- Treat the active endocrinopathy: aromatase inhibitors or tamoxifen for precocious puberty, antithyroid therapy for hyperthyroidism, axis-specific management for Cushing syndrome or growth hormone excess
- Bisphosphonates reduce bone pain in fibrous dysplasia; orthopedic management of fractures and deformity
- Monitor for vision and hearing loss when craniofacial fibrous dysplasia is present
GNAS = G proteiN, Alpha Subunit: The gene name encodes the G protein alpha subunit. "Mosaic w/ MoCune": McCune-Albright is a somatic mosaic disorder (germline is lethal). BBC, the 3 affected tissue types: Brain (pituitary), Bone (fibrous dysplasia, "McCune Albone"), Cutaneous ("McCutaneous-Albright", cafe-au-lait macules). Pituitary hormones are overproduced. "FLAT PiG": FSH/LH (early puberty), ACTH (Cushing), TSH (hyperthyroidism), GH (acromegaly). "Puberty is bright n' early with McCune Albright."