What's McCune-Albright syndrome?
McCune-Albright syndrome is a rare mosaic disorder caused by a GNAS gene change that arises after conception (post-zygotic), so it is present in only some of the body's cells and is not inherited or passed to children. It classically combines bone, skin, and hormone-gland features.
| Also indexed as | OMIM:174800, MONDO:0018919 |
|---|---|
| Features mapped | 11 |
| Treatments mapped | 7 |
| Published sources | 14 |
| Last reviewed | 2026-08-04 |
Signs and symptoms
Typified by somatic mosaicism
McCune-Albright syndrome is not inherited. It comes from a change in the GNAS gene that happens after conception (postzygotic), so it is present in only some of the body's cells. This patchy, cell-by-cell pattern is called somatic mosaicism, and it explains why the condition affects different tissues to different degrees.
Elevated circulating growth hormone concentration
McCune-Albright syndrome can involve other overactive hormone glands, including growth hormone excess, where the body makes too much of the hormone that controls growth.
Hyperthyroidism
Beyond early puberty, McCune-Albright syndrome can involve other overactive hormone glands. One of these is hyperthyroidism, an overactive thyroid gland.
Precocious puberty
Precocious puberty means signs of puberty start unusually early. In girls this can mean vaginal bleeding or spotting and breast development, and in boys enlargement of the testes and penis and early sexual behavior.
Hyperparathyroidism
Among the associated endocrine problems, the parathyroid glands can become overactive (hyperparathyroidism).
Increased circulating cortisol level
McCune-Albright syndrome can involve other overactive hormone glands, including Cushing syndrome, in which the body makes too much of the stress hormone cortisol.
Polyostotic fibrous dysplasia
Fibrous dysplasia is the bone change of McCune-Albright syndrome, where normal bone is replaced by weaker fibrous tissue. It can affect one bone or many, and often shows up as a limp or pain, and sometimes a bone that breaks easily.
Bone pain
Bone pain that is not caused by a fracture is more common in adults with this condition, but it can also occur in children.
Large cafe-au-lait macules with irregular margins
Café-au-lait spots are flat, light-brown skin patches. In McCune-Albright syndrome they are usually present from the newborn period, though it is more often the early puberty or the bone changes that first lead to medical attention.
Pathologic fracture
Because fibrous dysplasia weakens bone, affected bones can break on their own. The skeletal sites involved are set early in life, and fractures and bone deformity tend to be most pronounced in childhood.
Hypophosphatemia
In McCune-Albright syndrome, blood levels of the hormone FGF-23 tend to be higher, and low blood phosphate (hypophosphatemia) is more common.
How it is diagnosed
McCune-Albright syndrome, somatic, mosaic
Diagnosed using: GNAS mutation testing in affected tissue.
“Mutation detection strongly depends on sample type, reflecting disease mosaicism.”
McCune-Albright syndrome, somatic, mosaic
Diagnosed using: clinical and radiographic diagnosis.
“Diagnosis of MAS is usually established on clinical grounds.”
Treatment and management
What the research describes, not a recommendation. Treatment decisions belong with your clinician.
This covers treatments that appear in the published research mapped here. Investigational and experimental therapies are not included, so their absence is a boundary of this map, not a sign they do not exist.
bisphosphonates
Bisphosphonates are medicines that act on bone and are frequently used in the treatment of fibrous dysplasia.
Used to help with: Bone pain.
“Bisphosphonates have proven their effectiveness on bone pain and the limitation of fibrous dysplasia.”
aromatase inhibitors
Aromatase inhibitors are among the medicines used to treat the early puberty of McCune-Albright syndrome. In a series of girls with the condition, treatment that included aromatase inhibitors gave partial or complete control of puberty.
Used to help with: Precocious puberty.
“The patient initially presented with peripheral precocious puberty at age 1 and was treated with aromatase inhibitors and selective estrogen receptor modulator (SERM) until the age of 12 years for pubertal suppression.”
aromatase inhibitors
Aromatase inhibitors are among the medicines used to treat the early puberty of McCune-Albright syndrome. In a series of girls with the condition, treatment that included aromatase inhibitors gave partial or complete control of puberty.
Used to help with: McCune-Albright syndrome, somatic, mosaic.
“Treatment included medroxyprogesterone acetate, tamoxifen, aromatase inhibitors, and ketoconazole, individually or in combination for 5 ± 2.14 years, with partial or complete control of puberty.”
burosumab
Some fibrous dysplasia lesions make too much of a hormone called FGF-23, which causes the kidneys to lose phosphate and lowers blood phosphate, weakening bone. Burosumab is an antibody that blocks FGF-23. It is approved for other phosphate-wasting conditions and, in case reports, has shown promise for the low phosphate seen in McCune-Albright syndrome, though this use is still off-label.
Used to help with: Hypophosphatemia.
“Burosumab, a monoclonal antibody against FGF-23, is approved for X-linked hypophosphatemia and tumor-induced osteomalacia and has shown promise in case reports of pediatric and adult patients with MAS-related FGF-23-mediated hypophosphatemia.”
bisphosphonates
Bisphosphonates are medicines that act on bone and are frequently used in the treatment of fibrous dysplasia.
Used to help with: Polyostotic fibrous dysplasia.
“Bisphosphonates are frequently used in the treatment of FD.”
denosumab
Denosumab can quiet the activity of fibrous dysplasia bone lesions and improve how the bone looks on imaging. Its effect on pain is less certain, with mixed results across studies.
Used to help with: Polyostotic fibrous dysplasia.
“Denosumab has been shown to reduce skeletal lesion activity and improve radiographic bone density; however, there is mixed evidence regarding its effect on pain.”
zoledronic acid
Zoledronic acid is a bisphosphonate given by infusion. In children with fibrous dysplasia, the response on symptoms and on imaging has been described as promising, though larger trials are still needed to confirm its place in treatment.
Used to help with: Polyostotic fibrous dysplasia.
“This retrospective study evaluated the outcome and safety of long-term treatment with zoledronic acid, in both polyostotic and mono-ostotic fibrous dysplasia (FD) of children.”
What changes how it shows up
Carrying the genetic change is not the whole story. The factors below are described in the research mapped here as changing whether, or how strongly, the condition appears. They modulate how the genotype is expressed; they do not, on their own, cause or cure it.
somatic mosaicism
Because the GNAS change is present in only some cells (mosaicism), which cells carry it differs from person to person. This is why the condition looks so different between individuals and why a blood test can miss it.
Described as modulating: McCune-Albright syndrome, somatic, mosaic.
“Mosaicism leads to marked clinical heterogeneity and complicates molecular diagnosis.”
somatic GNAS activating mutation (mosaic)
McCune-Albright syndrome is driven by a gain-of-function change in the GNAS gene that happens after conception (postzygotic) rather than being inherited. GNAS makes the Gs-alpha protein, and the change makes that signaling protein overactive. Because the change arises in some cells but not others, the body is a mosaic, which is why the condition varies so much from person to person.
Described as modulating: McCune-Albright syndrome, somatic, mosaic.
“The central pathogenic mechanism involves postzygotic somatic gain-of-function mutations in the GNAS gene, which encodes the α subunit of the stimulatory G protein (Gsα).”
FGF23-mediated renal phosphate wasting
In McCune-Albright syndrome, the fibrous dysplasia lesions in bone can overproduce a hormone called fibroblast growth factor-23 (FGF-23). Excess FGF-23 makes the kidneys spill phosphate into the urine (renal phosphate wasting), which lowers blood phosphate (hypophosphatemia) and impairs bone mineralization. This is the mechanism behind the low phosphate seen in the condition and is the target of the antibody therapy burosumab.
Described as modulating: McCune-Albright syndrome, somatic, mosaic.
“FD lesions can overproduce fibroblast growth factor-23 (FGF-23), leading to renal phosphate wasting, hypophosphatemia, and impaired bone mineralization.”
How to read the evidence labels
Where this comes from
This guide is built from 14 published source(s). Every claim above links back to one of them. Click any source ID to read the original on PubMed.
Take it further
Printed, source-linked documents built from this condition's graph — ready to bring to an appointment or attach to a coverage request. Every claim carries its published source, the same as this guide.