Fibrous dysplasia/McCune-Albright syndrome

Fibrous dysplasia / McCune-Albright syndrome (FD/MAS), the result of an early embryonic postzygotic somatic activating pathogenic variant in GNAS (encoding the cAMP pathway-associated G protein Gαs [Gs alpha subunit]), is characterized by involvement of the skin, skeleton, and certain endocrine organs. However, because Gαs signaling is ubiquitous, additional tissues may be affected. Hyperpigmented skin macules are common and are usually the first manifestation of the disease, apparent at or shortly after birth. Fibrous dysplasia (FD), which can involve any part and combination of the craniofacial, axial, and/or appendicular skeleton, can range from an isolated, asymptomatic monostotic lesion discovered incidentally to severe, disabling polyostotic disease involving practically the entire skeleton and leading to progressive scoliosis, facial deformity, and loss of mobility, vision, and/or hearing. Endocrinopathies include gonadotropin-independent precocious puberty resulting from recurrent ovarian cysts in girls and autonomous testosterone production in boys; testicular lesions with or without associated gonadotropin-independent precocious puberty; thyroid lesions with or without non-autoimmune hyperthyroidism; growth hormone excess; FGF23-mediated phosphate wasting with or without hypophosphatemia in association with fibrous dysplasia; and neonatal hypercortisolism.

Full text of GeneReview (by section):

Summary

Diagnosis

Clinical Characteristics

Genetically Related (Allelic) Disorders

Differential Diagnosis

Management

Genetic Counseling

Resources

Molecular Genetics

Chapter Notes

References

Authors:

Vivian Szymczuk

Pablo Florenzano

Luis F de Castro

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