What are the other Names for this Condition? (Also known as/Synonyms)

• Albright Syndrome
• Albright's Disease
• Polyostotic Fibrous Dysplasia (POFD)

What is McCune-Albright Syndrome? (Definition/Background Information)

• McCune-Albright Syndrome (MAS) is a disorder that affects the skin, skeleton, and certain endocrine organs (hormone-producing tissues)
• Cafe-au-lait spots of the skin are common and are usually the first apparent sign of McCune-Albright Syndrome. The main skeletal feature is fibrous dysplasia, which ranges in severity and can cause various complications
• Early skeletal symptoms may include limping, pain, or fracture. Endocrine features may include precocious puberty; excess growth hormone; thyroid lesions with possible hyperthyroidism; Cushing syndrome; and renal phosphate wasting
• McCune-Albright Syndrome is not inherited. It is caused by a somatic mutation in a gene called GNAS, which is acquired after an egg is fertilized and only affects some of the body's cells and tissues
• Management depends on the symptoms in each person and may include optimizing function related to fractures and deformities; medications; and surgery

(Source: McCune-Albright Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets McCune-Albright Syndrome? (Age and Sex Distribution)

• McCune-Albright Syndrome is a rare disorder, with a prevalence between 1 in 100,000 to 1 in 1,000,000
• The presentation of symptoms may occur in childhood
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for McCune-Albright Syndrome? (Predisposing Factors)

• Currently, no risk factors have been clearly identified for McCune-Albright Syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of McCune-Albright Syndrome? (Etiology)

McCune-Albright Syndrome (MAS) is caused by somatic mutations in the GNAS gene.

• This gene provides instructions for making part of a protein that influences many cell functions by regulating hormone activity
• GNAS mutations that cause MAS result in a protein that causes the enzyme adenylate cyclase to always be "on"
• This leads to over-production of several hormones, resulting in the signs and symptoms of MAS
• McCune-Albright Syndrome (MAS) is not inherited. It is caused by a random, somatic mutation in the GNAS gene
• Mutations that cause MAS occur very early in development, after an egg is fertilized (conception)
• These mutations are not present in the egg or sperm of the parents of affected children
• Because these mutations are acquired after conception, some of the body's cells have a normal GNAS gene, while other cells have the mutated gene. This phenomenon is called mosaicism

(Source: McCune-Albright Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

What are the Signs and Symptoms of McCune-Albright Syndrome?

The signs and symptoms of McCune-Albright Syndrome relate to the skeleton (bones), the endocrine organs (hormone-producing tissues), and the skin. Symptoms can range from mild to severe

Skeletal symptoms associated with McCune-Albright Syndrome include fibrous dysplasia, where the normal bone is replaced by softer, fibrous tissue.

Endocrine symptoms of McCune-Albright Syndrome:

• Early puberty (also called precocious puberty) 
• Thyroid disease, such as goiter or hyperthyroidism
• Increased production of growth hormone leading to acromegaly
• Cushing’s syndrome 
• Testicular abnormalities in males, such as large testes 
• Phosphate wasting: Increased production of the hormone FGF23 can result in renal tubulopathy

Skin symptoms of McCune-Albright Syndrome include cafe-au-lait spots.

Based on the frequency of symptoms observed, the following information may be noted:

Very frequently present symptoms in 80-99% of the cases:

• Bone pain 
• Generalized hyperpigmentation 
• Hypophosphatemia
• Multiple cafe-au-lait spots 
• Precocious puberty
• Recurrent fractures
• Reduced bone mineral density
• Skeletal dysplasia

Occasionally present symptoms in 5-29% of the cases:

• Abnormality of dental enamel
• Abnormality of the palate
• Abnormality of vision
• Carious teeth
• Elevated hepatic transaminases
• Goiter 
• Hearing abnormality
• Hyperparathyroidism
• Hyperthyroidism
• Increased circulating cortisol level 
• Kyphosis
• Long penis
• Macrocephaly
• Macroorchidism
• Mandibular prognathia 
• Neoplasm of the breast
• Neoplasm of the thyroid gland 
• Open bite
• Optic atrophy 
• Polycystic ovaries 
• Prolonged bleeding time 
• Sarcoma 
• Tall stature
• Testicular neoplasm

(Source: McCune-Albright Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

How is McCune-Albright Syndrome Diagnosed?

McCune-Albright Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Molecular genetic testing for GNAS gene mutation

The diagnosis of McCune-Albright syndrome (MAS) can be made in people who have two or more of the following typical clinical features of MAS:

• Café-au-lait skin spots with characteristic features 
• Polyostotic fibrous dysplasia (involving more than one bone) or GNAS mutation-proven monostotic fifbrous dysplasia (involving a single bone)
• Any of the following endocrine abnormalities (each with specific characteristics):
  • Gonadotropin-independent precocious puberty
  • Testicular lesions
  • Thyroid lesions
  • Growth hormone excess
  • Phosphate wasting
  • Neonatal hypercortisolism (Cushing's syndrome)

(Source: McCune-Albright Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of McCune-Albright Syndrome?

The complications of McCune-Albright Syndrome may include:

• Severe pain
• Blindness
• Hearing loss
• Progressive scoliosis 
• Loss of mobility 
• Severe disfigurement
• Impaired kidney function
• Malignant cancers

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is McCune-Albright Syndrome Treated?

There is no cure for McCune-Albright Syndrome, and the treatment methods are tailored to manage pain, vision impairment and disfigurement. Treatment methods may include:

• Bisphosphonates for the treatment of fibrous dysplasia
• Medical therapy to control symptoms associated with abnormal levels of hormone
• Surgery to manage bone problems that cause impaired vision, debilitating pain or severe disfigurement
• Physical therapy and strengthening exercises to minimize risk of fracture

How can McCune-Albright Syndrome be Prevented?

• Currently, McCune-Albright Syndrome may not be preventable, since it is a genetic disorder, and the risk factors are not clearly known
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of McCune-Albright Syndrome? (Outcomes/Resolutions)

• The prognosis of McCune-Albright Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• The condition is not life-threatening and the affected individuals are reported to have a normal lifespan
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• The prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for McCune-Albright Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/