McCune-Albright Syndrome (MAS)

What is MAS?

MAS is a genetic disorder that affects the skin, bones, and the production of certain hormones. Because of its effects on hormones, MAS often causes early puberty in girls. There are also other distinctive symptoms, such as light-brown birthmarks and unusual formations of the bones.¹

MAS symptoms can vary from mild to severe. They may begin at birth or later in childhood.¹

Main Symptoms

Many people with MAS have the following symptoms:

• Café-au-lait spots
  Café-au-lait (French for "coffee with milk") spots, which are light-brown birthmarks. The birthmarks^2,3:
  • Are usually are present at birth
  • May be hard to see on dark skin
  • Often appear on one side of the body
  • Have jagged edges sometimes referred to as the "coast of Maine"
• Polyostotic fibrous dysplasia^2,3
  A person with polyostotic fibrous dysplasia (PFD) has scar-like tissue, or fibrous tissue, in his or her bones. PFD usually occurs on one side of the body in weight-bearing bones, such as leg bones. PFD may cause:
  • Bone pain
  • Cancer of the bone (very rare)
  • Abnormal bone growth
  • Fractures
  • Limping
  • Scoliosis a curvature of the spine
  • Uneven growth, including uneven growth of the face

In addition, bone lesions in the skull may pinch nerves that affect a person’s ability to see and hear.³

• Precocious puberty^2,3,4
  Precocious puberty is when sexual and physical changes occur earlier than normal.
  
  Girls with MAS may experience such symptoms as:
  • Early menstrual bleeding, usually before 2 years of age
  • Early breast growth
  • Beginning to grow faster
  Boys with MAS are less likely to experience early puberty. Symptoms in boys include:
  • Faster than normal growth of penis or testicles
  • Premature sexual behavior
  • Early growth of armpit or pubic hair

Additional Symptoms

Additional features of MAS may include (but are not limited to)^1,2,3,6:

• Overproduction of growth hormone from the pituitary gland
• Cushing syndrome, overactivity of the adrenal glands, leading to an increase in stress hormone levels
• Formation of benign (noncancerous) tumors in the testicles, called Sertoli cell hyperplasia and Leydig cell hyperplasia
• Hyperthyroidism, an overactive thyroid gland
• Loss of phosphate in the urine, leading to low blood phosphorus levels
• Liver disease

Number of People Affected

MAS is rare, affecting between 1 in every 100,000 to 1 million live births worldwide.¹

Who is at risk?

Because the genetic change or mutation that causes MAS occurs at random very early in fetal development, MAS is not an inherited disease, meaning parents do not pass it on to their children.¹

MAS likely occurs equally in males and females.

MAS is a genetic disorder, which means that a change, also called a mutation, in a gene causes it. Genes are in the chromosomes of almost all human cells, and they code for each cell’s specialized actions. The mutation that causes MAS leads to errors in the functioning of certain cells.¹

MAS is not an inherited disease, meaning parents do not pass it on to their child, because the mutation occurs randomly while an embryo is developing.

GNAS Gene Mutation

MAS is caused by a mutation in the GNAS gene. The GNAS gene codes for one part of the G protein, which is short for guanine nucleotide-binding protein. This protein plays an important role in triggering many other cell processes. One of these processes is to turn off an enzyme called the adenylate cyclase enzyme. The mutated form of the G protein cannot turn this enzyme off, so the constantly active adenylate cyclase enzyme causes excess production of other hormones, resulting in the symptoms of MAS.¹

Mosaicism

The GNAS mutation happens after an embryo begins to form, and not when the mother’s egg or the father’s sperm is formed. Therefore, not all of the embryo’s cells have the mutation. This is called mosaicism. The severity of MAS symptoms depends on the number and location of cells containing the mutated GNAS gene.¹

MAS is caused by a mutation in the GNAS gene. The mutation leads to errors in the functioning of certain cells.¹

The GNAS gene codes for one part of the G protein, which is short for guanine nucleotide-binding protein. This protein plays an important role in triggering many cell processes, including the process that "turns off" an enzyme called the adenylate cyclase enzyme. The mutated form of the G protein cannot turn off the enzyme. High levels of active adenylate cyclase cause excess production of other hormones, resulting in the symptoms of MAS.¹

Not every cell in the body is exactly the same, so some cells may have the GNAS mutation while others do not. This is called mosaicism. The severity of MAS symptoms depends on the number of cells with the mutated GNAS gene and the location of those cells in the body.¹

A person is diagnosed with MAS if he or she has a combination of any of the following symptoms¹:

• Café-au-lait (French for "coffee with milk") spots, which are light brown birthmarks
• Polyostotic fibrous dysplasia (PFD), which is a bone irregularity
• Precocious puberty, which is premature development in a child
• Hyperthyroidism, which is an overactive thyroid gland
• Growth hormone excess
• Cushing syndrome, an overactivity of the adrenal glands
• Sertoli cell hyperplasia and Leydig cell hyperplasia, which are tumors in the testicles

Read more about the symptoms of MAS.

A healthcare provider may use X-rays to examine bones for PFD. He or she may perform ultrasounds to look for an abnormal appearance of the thyroid or testicles. Blood tests may be done to check for abnormal hormone levels. He or she may take a small sample or biopsy of abnormal bone tissue and analyze it to confirm PFD, thereby confirming MAS.²

A genetic test is also available to detect the GNAS gene mutation, but it is often not reliable for diagnosing MAS. The diagnosis of MAS is made clinically, based on the presence of characteristic features.³ Learn more about MAS and genetic testing.

Symptoms and severity of MAS vary, so diagnosis may occur at birth or later in childhood.⁴

Treatment for MAS depends on the extent and the severity of a person’s symptoms. (Learn more about the symptoms associated with MAS.). For example, healthcare providers may recommend medication for endocrine problems, or surgery for bone issues.¹

• Medications, including agents that block the production of certain hormones, may help address several conditions associated with MAS, including¹:
  • Cushing syndrome
  • Hyperthyroidism
  • Growth hormone excess
  • Low blood phosphates
  • Precocious puberty
  • Bone pain
• Surgery may help address¹:
  • Bone deformities or uneven growth
  • Cushing syndrome, by removing adrenal glands
  • Hyperthyroidism, by removing the thyroid gland
  • Hearing and vision problems, such as by relieving pinched nerves

Healthcare providers may also recommend bisphosphonates, or drugs that help prevent bone loss. More research is needed to determine the role of these medications in MAS; at present, they are often recommended to treat pain from the PFD caused by MAS. In addition, strengthening exercises may help build muscle around bones affected by PFD, which can reduce the risk of bone fractures.¹