Disease Directory McCune-Albright Syndrome
Connective Tissue

McCune-Albright Syndrome

Also known as: polyostotic fibrous dysplasia, McCune-Albright, GNAS mosaic mutation

Prevalence

1 in 100,000–1,000,000

Onset

Congenital (postzygotic mutation); clinical presentation in infancy to childhood

Type

Genetic — somatic mosaic (postzygotic, not heritable)

Gene

GNAS

About McCune-Albright Syndrome

McCune-Albright syndrome results from a somatic activating mutation in GNAS, encoding the Gsalpha subunit of heterotrimeric G-proteins, arising postzygotically and thus present in mosaic distribution throughout affected tissues. The classic triad consists of polyostotic fibrous dysplasia of bone (fibrous replacement of medullary bone predisposing to pathological fractures and deformity), cafe-au-lait skin macules with irregular borders, and autonomous endocrine hyperfunctioning of the gonads, thyroid, adrenal cortex, or pituitary. Clinical severity is highly variable and determined by the timing of the postzygotic mutation and the tissues in which the mutant clone is represented.

Common Clinical Features

Polyostotic fibrous dysplasia causing bone pain, deformity, and pathological fractures Cafe-au-lait macules with irregular (coast of Maine) borders Gonadotropin-independent precocious puberty (especially in girls) Hyperthyroidism from autonomous thyroid nodules Cushing syndrome from adrenocortical hyperplasia (in infants) Growth hormone excess and acromegaloid features Phosphate wasting and rickets secondary to FGF23 overproduction

Clinical Trial Eligibility Tips

What to know before applying to McCune-Albright Syndrome trials.

Blood or tissue for GNAS mutation testing should ideally include DNA from affected tissue (bone or affected skin), as the mosaic mutation may not be detectable in peripheral blood leukocytes — clarify the testing source with the genetic laboratory.

Baseline bone scintigraphy (technetium scan) or skeletal survey documenting extent and distribution of fibrous dysplasia lesions is standard prior to enrolment in bone-targeted trials.

Endocrine assessments (LH, FSH, oestradiol or testosterone, IGF-1, thyroid function, morning cortisol) are required at screening as autonomous hyperfunctioning affects safety and efficacy endpoints.

Patient Resources

Patient Organization

Fibrous Dysplasia Foundation

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Natural History Registry

FD/MAS Alliance Registry

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Orphanet

European reference resource for rare diseases (ORPHA:562)

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NORD

National Organization for Rare Disorders

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Find recruiting McCune-Albright Syndrome trials

Search 500,000+ studies from ClinicalTrials.gov, filtered for McCune-Albright Syndrome. Updated daily.

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