McCune-Albright Syndrome

McCune-Albright syndrome (MAS) is a rare genetic condition that affects the bones, skin, and hormone-producing (endocrine) system. All people with McCune-Albright syndrome have fibrous dysplasia, so the combined condition is referred to as fibrous dysplasia/McCune-Albright syndrome (FD/MAS). The condition can vary widely from person to person, ranging from mild to complex, depending on which tissues are affected.

MAS is not inherited or contagious. It results from a random change in a gene called GNAS, which occurs after conception. This mutation causes some cells in the body to act abnormally, leading to a wide range of effects on bones, hormones, and pigmentation.

What Is McCune-Albright Syndrome?

McCune-Albright syndrome was first described in the 1930s and is defined by a classic triad:

1. Fibrous dysplasia of bone – areas where normal bone is replaced by fibrous tissue.
2. Café-au-lait spots – this term is dated, but is commonly used to describe the darker-brown birthmarks on the skin with irregular borders.
3. Endocrine hyperfunction – overactivity of one or more hormone-producing glands.

Not everyone with MAS has all three features. Some may have only one or two, but the underlying cause—the same GNAS mutation—is shared by all.¹

Causes and How It Develops

The GNAS gene provides instructions for making a protein that helps regulate hormone signaling. A random mutation in this gene activates it constantly, causing excess cell activity in certain tissues. Because the mutation happens after conception, only some cells carry it—this is called mosaicism.²

The timing and location of the mutation determine which systems are affected:

• If it occurs in bone-forming cells, fibrous dysplasia develops.
• If it occurs in endocrine tissues, hormonal overactivity can appear.
• If it occurs in skin cells, café-au-lait spots form.

The combination of these effects is what defines FD/MAS.³

Common Signs and Symptoms

Because MAS affects multiple systems, symptoms can vary greatly between individuals.

Bone Involvement

Many people with MAS have polyostotic fibrous dysplasia, meaning multiple bones are affected. This can cause pain, fractures, bone deformity, and in some cases, craniofacial changes. Bone lesions often appear in childhood and may stabilize after growth ends.⁴

Skin Involvement

Café-au-lait spots are usually present from birth or early childhood. These patches are darker brown than the skin tone with uneven, “coast of Maine” borders, and typically appear on one side of the body.⁵

Endocrine (Hormonal) Involvement

The endocrine system controls growth, metabolism, and many body functions. In MAS, one or more glands may become overactive. Common endocrine issues include:

• Precocious puberty: Early onset of puberty, often before age 8.⁶
• Thyroid overactivity: Can cause weight loss, rapid heartbeat, or anxiety.⁷
• Growth hormone excess: This is often associate with bone lesion activity.
• Adrenal overactivity: Rare but can cause Cushing’s syndrome in infants.⁸
• Low phosphate levels (hypophosphatemia): Can weaken bones and teeth.

Each person’s hormonal pattern is unique, and the combination of bone, skin, and endocrine findings determines how MAS is managed.

Diagnosis

Diagnosis is based on a combination of clinical findings, imaging, and lab tests.

Clinical Evaluation

Doctors look for the presence of two or more features from the classic triad, bone, skin, or endocrine. Because MAS can affect multiple organs, evaluation often involves a multidisciplinary team.⁹

Imaging

• X-rays or bone scans identify fibrous dysplasia lesions.
• MRI or CT scans can determine where bone lesions are present and can assess craniofacial involvement or monitor endocrine tumors.¹⁰

Lab Tests

• Blood and urine tests check hormone levels such as estrogen, testosterone, thyroid hormones, growth hormone, and cortisol.
• Low phosphate levels may indicate FGF23-related phosphate wasting.

Genetic Testing

Testing for the GNAS mutation can confirm the diagnosis, but it may not always be detected in blood due to mosaicism. Tissue or lesion testing can sometimes provide a clearer result.¹¹

Treatment and Management

There is no single treatment for MAS, since the condition affects several systems.
Management focuses on controlling symptoms, correcting hormone imbalances, and protecting bone health. Reviewing the full treatment guidelines with your care team is strongly recommended.

Hormonal Treatment

While the hormonal symptoms can be unsettling, most are managed through medications. It is recommended that a knowledgeable endocrinologist oversee care for these symptoms.

Bone Management

Bone lesions are managed similarly to fibrous dysplasia alone. Pain control, physical therapy, and, when necessary, orthopedic surgery are used to stabilize fractures or correct deformities. Bisphosphonates may relieve bone pain for some patients, but do not stop lesion growth and may come with complications.¹⁷

Supportive Care

People with FD/MAS benefit from ongoing monitoring by endocrinologists, orthopedic specialists, and dental or craniofacial teams. Psychological support and connection to rare disease communities can also help with long-term wellbeing.

Living With FD/MAS

Living with MAS can be physically and emotionally challenging. Symptoms can change over time, and care often involves multiple specialists. Regular follow-up visits help ensure hormone levels remain stable and bone lesions are monitored. With coordinated care, many individuals live full, active lives.

The FD/MAS Alliance offers educational resources, patient stories, and opportunities to participate in research and advocacy. Staying connected with these networks can help patients and families feel supported and informed.

Key Takeaways

McCune-Albright syndrome is caused by a random mutation in the GNAS gene that can affect the bones, skin, and hormone glands in different ways. It is not inherited or contagious, and the range of symptoms varies widely from person to person. Some people experience only mild issues, while others may require lifelong care and monitoring. Managing hormone levels and protecting bone health are central to improving quality of life and preventing complications. With coordinated care and community support, individuals with FD/MAS can lead active, fulfilling lives.

Related Pages:

• What Is Fibrous Dysplasia?
• Treatment Options for FD/MAS
• Living With FD/MAS
• FD/MAS Toolkit

Frequently Asked Questions

Is McCune-Albright syndrome inherited?
No. It occurs from a random gene mutation after conception, not from parents. The mutation affects only some cells in the body (mosaicism).

Can MAS develop later in life?
Most signs appear in early childhood, but some hormonal problems may develop later. Many people are diagnosed because of early puberty, bone issues, or café-au-lait spots.

Does MAS always include fibrous dysplasia?
All people with MAS have some degree of fibrous dysplasia, though the severity varies. The combined condition is referred to as FD/MAS.

Can MAS be cured?
There is currently no cure, but symptoms can be managed effectively. Ongoing research aims to find treatments that target the underlying genetic pathway.

Is it safe to have children with MAS?
Yes. MAS is not inherited and does not increase the chance of passing the condition to children.

References

1. Orphanet Journal of Rare Diseases – Overview of MAS
2. Endocrine Reviews, 2020 – GNAS and FD/MAS Mechanisms
3. NCBI Bookshelf – FD/MAS Overview
4. PMC, 2024 – Clinical Spectrum of FD/MAS
5. Orphanet Journal of Rare Diseases – Skin Manifestations
6. Journal of Clinical Endocrinology & Metabolism – Precocious Puberty in MAS
7. Frontiers in Endocrinology – Thyroid Abnormalities in MAS
8. Orphanet Journal of Rare Diseases – Adrenal and Growth Hormone Findings
9. PMC, 2024 – Diagnosis and Care of FD/MAS
10. Insights Imaging, 2018 – Imaging of FD/MAS
11. PMC, 2024 – Genetic Testing Limitations in MAS
12. OUP Endocrine Practice – Managing Precocious Puberty
13. Orphanet Journal of Rare Diseases – Thyroid Disease in MAS
14. Frontiers in Endocrinology, 2025 – Growth Hormone Treatment in FD/MAS
15. Orphanet Journal of Rare Diseases – Adrenal Manifestations
16. PMC – Phosphate Wasting in MAS
17. PMC – Bone Pain Management in FD/MAS