ConditionHormones & metabolism
McCune-Albright Syndrome
McCune-Albright syndrome (MAS) is a rare condition caused by a gene change (in GNAS) that happens after conception, so only some of the body's cells are affected. It classically combines three features: fibrous dysplasia (weak, scar-like bone), cafe-au-lait skin patches with jagged edges, and overactive hormone glands, most often causing early puberty in girls. Severity ranges from mild to severe. It is not inherited, and treatment targets each affected area.
Also called: MAS, McCune-Albright disease, polyostotic fibrous dysplasia with endocrinopathy
At a glance
- What it is
- A mosaic GNAS gene change causing bone, skin and hormone problems.
- Classic triad
- Fibrous dysplasia, cafe-au-lait macules, endocrine overactivity.
- Common hormone effects
- Early puberty (especially girls), hyperthyroidism, growth hormone excess, phosphate wasting.
- Bone problems
- Pain, fractures, deformity (shepherd's crook femur), facial asymmetry.
- Inheritance
- Not inherited; arises by chance during early development.
- Treatment
- Hormone-blocking medicines, surgery for some bone lesions, pain control, monitoring.
When to get help
See a doctor within a day or two
- Sudden vision loss, eye bulging or severe headache in someone with skull fibrous dysplasia
- A bone fracture after minimal injury, or new severe bone pain
- Vaginal bleeding or breast development in a young girl
Book a routine appointment
- Large, irregular light brown birthmarks plus early puberty signs, bone pain or limp in a child
- Breast development before age 8 or pubic hair before age 9 in girls, or genital enlargement before 9 in boys
- Facial or jaw asymmetry, or a bony lump on the skull
- Rapid growth, large hands or feet, or coarsening of facial features
What causes McCune-Albright syndrome
MAS is caused by a somatic (post-zygotic) mutation in the GNAS gene. The change happens in one cell early in embryonic development, so the resulting person is a mosaic: some tissues carry the change and others do not. This explains why features vary greatly and why it is not passed on to children.
The GNAS change leaves a signaling protein (Gs alpha) permanently switched on. In affected cells, this drives overgrowth and overactivity: bone-forming cells make fibrous tissue instead of normal bone, pigment cells make extra melanin, and hormone glands work independently of normal control.
Features
Fibrous dysplasia of bone
Fibrous dysplasia replaces normal bone with fibrous, weaker tissue. It may affect one bone or many (polyostotic), most often the skull and face, thighbones, shinbones, ribs and pelvis. Effects include:
- bone pain
- fractures, often in childhood
- limb deformity, such as a bent thighbone (shepherd's crook deformity) and limping
- facial asymmetry, bony swelling, dental problems
- rarely, compression of the optic nerve or hearing loss
Cafe-au-lait macules
Cafe-au-lait macules in MAS are light to dark brown flat patches with jagged, irregular borders ("coast of Maine"), often on one side of the body and stopping at the midline. In contrast, the spots in neurofibromatosis type 1 have smooth borders ("coast of California").
Endocrine (hormone) problems
| Problem | Effect |
|---|---|
| Gonadotropin-independent precocious puberty | Girls: recurrent ovarian cysts, breast development, vaginal bleeding, sometimes in infancy; boys: less common, testicular enlargement |
| Hyperthyroidism | Weight loss, fast heart rate, goiter |
| Growth hormone excess | Gigantism in children, acromegaly in adults; worsens skull fibrous dysplasia |
| Phosphate wasting (hypophosphatemia) | Bone pain, rickets or osteomalacia, more fractures |
| Neonatal Cushing syndrome | Rare, serious, in infancy |
Other possible features
- liver disease, pancreatitis and gut polyps
- increased risk of certain tumors (breast, thyroid, bone) in some people
Diagnosis
MAS is diagnosed clinically when someone has fibrous dysplasia plus at least one other typical feature, or two or more non-bone features.
- Physical exam: skin, growth and puberty assessment.
- Imaging: X-rays, CT of the skull, and a bone scan to find all fibrous dysplasia sites.
- Hormone tests: sex hormones, thyroid function, growth hormone and IGF-1, cortisol.
- Blood and urine tests: phosphate, FGF23, vitamin D, calcium.
- Pelvic or testicular ultrasound.
- Genetic testing: GNAS testing of affected tissue can confirm the diagnosis; blood tests may miss it because of mosaicism.
Treatment
There is no cure, but each feature can be treated:
- Precocious puberty: aromatase inhibitors (such as letrozole) in girls; anti-androgens and aromatase inhibitors in boys.
- Hyperthyroidism: methimazole, then often thyroid surgery or radioactive iodine.
- Growth hormone excess: somatostatin analogs, pegvisomant; sometimes pituitary surgery or radiation.
- Phosphate wasting: phosphate and active vitamin D supplements.
- Fibrous dysplasia: orthopedic surgery for fractures and deformities (often rods rather than bone grafts), bisphosphonates for bone pain, and physical therapy. Skull lesions are usually monitored, with surgery only for symptoms.
- Pain management.
- Regular monitoring by endocrinology, orthopedics, ophthalmology and ENT.
Outlook
Life expectancy is generally normal for most people, though quality of life depends on the extent of bone disease and hormone control. Fibrous dysplasia lesions usually become less active after puberty. Lifelong follow-up helps catch new hormone problems and complications early.
Frequently asked questions
What is McCune-Albright syndrome?
McCune-Albright syndrome is a rare condition caused by a GNAS gene change present in some of the body's cells. It typically causes fibrous dysplasia of bone, irregular cafe-au-lait birthmarks and overactive hormone glands, most often leading to early puberty.
Is McCune-Albright syndrome inherited?
No. The gene change happens by chance in a single cell early in development after conception. It is not inherited from parents and is not passed on to children, because it is not present in all cells.
What are the symptoms of McCune-Albright syndrome?
Common symptoms include bone pain, fractures and deformities from fibrous dysplasia, light brown patches with jagged edges, early puberty with vaginal bleeding in girls, and other hormone problems such as an overactive thyroid or excess growth hormone.
How is McCune-Albright syndrome treated?
Treatment depends on the features present. Medicines block excess hormones, surgery repairs fractures and deformities, bisphosphonates can ease bone pain, and phosphate supplements treat phosphate loss. Care is coordinated by several specialists.
What do cafe-au-lait spots look like in McCune-Albright syndrome?
They are flat, light to dark brown patches with jagged, irregular borders, often described as resembling the coast of Maine. They often appear on one side of the body and may stop at the midline of the back or chest.
Sources
This guide was written from current patient and clinical guidance, including:
- National Institutes of Health (NIDCR): Fibrous dysplasia and McCune-Albright syndrome
- Orphanet Journal of Rare Diseases: Best practice management guidelines for fibrous dysplasia/McCune-Albright syndrome (international consortium)
- National Organization for Rare Disorders (NORD): McCune-Albright syndrome
- MedlinePlus Genetics: McCune-Albright syndrome
- FD/MAS Alliance: Patient resources