McCune-Albright syndrome

Polyostotic fibrous dysplasia

A rare genodermatosis characterized by the classical triad of café-au-lait macules with irregular borders, polyostotic fibrous dysplasia, and precocious puberty. It is caused by postzygotic activating mutations in the GNAS1 gene, resulting in genomic mosaicism.

Very rare. The disorder occurs sporadically due to postzygotic mutations and is not inherited. Onset typically occurs in early childhood.

Belongs to the group of rare genetic diseases with dermatological, skeletal, and endocrine manifestations.

Caused by a postzygotic activating mutation in the GNAS1 gene (chromosome 20q13.32), which encodes the Gs-alpha protein subunit. This results in constitutive activation of adenylate cyclase, elevated cAMP levels, and multiple endocrine abnormalities.

• Segmental café-au-lait macules with jagged “coast of Maine” borders, often following Blaschko's lines

• Precocious puberty (especially in girls)

• Polyostotic fibrous dysplasia with bone deformities, pain, and increased fracture risk

• Endocrinopathies including hyperthyroidism, Cushing’s syndrome, acromegaly, and hypophosphatemia

• Rarely, gigantism

Clinical diagnosis is based on the typical triad.

• Genetic testing (GNAS1 mutation in affected tissue)

• Endocrinological evaluation and hormone panels

• Imaging: skeletal scintigraphy, X-rays, MRI for fibrous dysplasia

Café-au-lait macules typically follow Blaschko's lines and are often unilateral. Bone involvement is usually asymmetrical, affecting the skull, facial bones, femur, and ribs.

Early signs of puberty, pathological fractures, congenital or early-onset segmental pigmentation, and abnormal growth patterns.

Not required for diagnosis. If performed: increased basal melanin deposition without melanocytic atypia.

• Severe bone deformities and recurrent fractures

• Endocrine dysfunction with systemic complications

• Rare malignant transformation (e.g., osteosarcoma)

• Psychosocial burden due to visible disfigurement or precocious puberty

Not preventable. Genetic counseling may be useful in differential diagnosis despite the absence of inheritance.

Highly variable. Severe courses may occur due to endocrine or extensive skeletal involvement. Isolated cutaneous manifestations have a favorable prognosis.

• Dermatologic: no specific therapy required

  • Cosmetic lightening of café-au-lait macules with hydroquinone, azelaic acid, or laser therapy if desired

• Endocrinologic: regular monitoring and treatment tailored to endocrine involvement (e.g., GnRH analogs, antithyroid medications)

• Orthopedic: fracture prevention and surgical correction if needed

• Pain management and supportive care

1. Schouten BJ, Suliman HM. Polyostotic fibrous dysplasia. JBR-BTR. 2013;96(4):246–7.

2. Lietman SA, Levine MA. Fibrous dysplasia. Pediatr Endocrinol Rev. 2013;10 Suppl 2:389–96.

3. Martin-Carreras T, Sanchez E, Bancroft LW. Polyostotic fibrous dysplasia. Orthopedics. 2014;37(11):722–82.

4. Wu FL, et al. Polyostotic fibrous dysplasia involving the thoracic spine with myelopathy. Spine J. 2014;14(1):e11–5.

5. Paul SM, et al. Disease severity and walking performance in fibrous dysplasia. Bone. 2014;60:41–7.

6. Boyce AM, Collins MT. Fibrous dysplasia/McCune-Albright syndrome. Best Pract Res Clin Endocrinol Metab. 2011;25(1):69–82.

7. Dumitrescu CE, Collins MT. McCune-Albright syndrome. Orphanet J Rare Dis. 2008;3:12.

8. Weinstein LS. Gsα mutations in Albright hereditary osteodystrophy and McCune-Albright syndrome. J Clin Endocrinol Metab. 2001;86(10):4630–6.

9. Collins MT. Spectrum and natural history of fibrous dysplasia. J Bone Miner Res. 2006;21 Suppl 2:P99–104.

10. Lee JS, et al. Clinical guidelines for craniofacial fibrous dysplasia. J Bone Miner Res. 2012;27(3):544–52.