McCune-Albright syndrome

Información en español Title

Other Names:

MAS; Albright syndrome; Albright's disease; MAS; Albright syndrome; Albright's disease; PFD; POFD; McCune Albright syndrome; Polyostotic fibrous dysplasia See More

Categories:

Congenital and Genetic Diseases; Endocrine Diseases; Female Reproductive Diseases; Congenital and Genetic Diseases; Endocrine Diseases; Female Reproductive Diseases; Musculoskeletal Diseases; Rare Cancers; Skin Diseases See More

Summary Summary

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 MAS. The main skeletal feature is fibrous dysplasia, which ranges in severity and can cause various complications.^[1] Early skeletal symptoms may include limping, pain, or fracture.^[2] Endocrine features may include precocious puberty; excess growth hormone; thyroid lesions with possible hyperthyroidism; Cushing syndrome; and renal phosphate wasting.^[1]^[2] MAS is not inherited.^[1] 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.^[3] Management depends on the symptoms in each person and may include optimizing function related to fractures and deformities; medications; and surgery.^[1]

Last updated: 8/28/2017

Symptoms Symptoms

Signs and symptoms of McCune-Albright syndrome (MAS) relate to the skeleton (bones), the endocrine organs (hormone-producing tissues), and the skin. Symptoms can range from mild to severe.^[4]

Skeletal symptoms may include:

Fibrous dysplasia - Normal bone is replaced by softer, fibrous tissue.^[4] This may lead to limping, pain, fractures, progressive scoliosis, uneven growth, facial deformity, and loss of mobility.^[1]^[4]^[5]

Endocrine symptoms may include:

Early puberty (also called precocious puberty) - Girls with MAS can have menstrual bleeding by age 2 (as early as 4-6 months in some), many years before breast enlargement and pubic hair growth begin.^[4]^[5]^[6] Early-onset menstruation is thought to be due to excess estrogen that may be produced by ovarian cysts.^[5] Less commonly, boys with MAS also experience early puberty.^[4]^[5]^[6]
Thyroid disease - The thyroid gland may become enlarged (called a goiter) or develop masses called nodules. About half of people with MAS have hyperthyroidism.^[4]^[5]
Increased production of growth hormone - The pituitary gland may produce too much growth hormone. This can result in acromegaly.^[4]^[5]
Cushing’s syndrome - Rarely, people with MAS produce too much cortisol in the adrenal glands. This can cause weight gain in the face and upper body, slowed growth, fragile skin, fatigue, and other health problems.^[4]^[5]
Testicular abnormalities in males - Testicular abnormalities are seen in the majority of males with MAS (~85%), and typically manifest as abnormally large testes (macro-orchidism).^[1]
Phosphate wasting - Increased production of the hormone FGF23 can result in renal tubulopathy, impairing the kidneys' ability to function properly.

Skin symptoms may include:

Cafe-au-lait spots - People with MAS usually have light brown patches of skin. These spots often appear on one side of the body and may be present from birth.^[4]^[5]

Less common features of MAS may include hepatitis; gastroesophageal reflux or gastrointestinal polyps; pancreatic complications such as pancreatitis; intramuscular myxomas (benign tumors); and cancers. Cancers that have been associated with MAS include bone, thyroid, testicular, and breast. Precocious puberty and growth hormone excess may contribute to an increased risk of cancer.^[1]

Last updated: 9/9/2016

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Bone pain	Very frequent (present in 80%-99% of cases)
Generalized hyperpigmentation	Very frequent (present in 80%-99% of cases)
Hypophosphatemia	Very frequent (present in 80%-99% of cases)
Multiple cafe-au-lait spots	Very frequent (present in 80%-99% of cases)
Precocious puberty	Very frequent (present in 80%-99% of cases)
Recurrent fractures	Very frequent (present in 80%-99% of cases)
Reduced bone mineral density	Very frequent (present in 80%-99% of cases)
Skeletal dysplasia	Very frequent (present in 80%-99% of cases)
Abnormality of dental enamel	Occasional (present in 5%-29% of cases)
Abnormality of the palate	Occasional (present in 5%-29% of cases)
Abnormality of vision	Occasional (present in 5%-29% of cases)
Carious teeth	Occasional (present in 5%-29% of cases)
Elevated hepatic transaminases	Occasional (present in 5%-29% of cases)
Goiter	Occasional (present in 5%-29% of cases)
Hearing abnormality	Occasional (present in 5%-29% of cases)
Hyperparathyroidism	Occasional (present in 5%-29% of cases)
Hyperthyroidism	Occasional (present in 5%-29% of cases)
Increased circulating cortisol level	Occasional (present in 5%-29% of cases)
Kyphosis	Occasional (present in 5%-29% of cases)
Long penis	Occasional (present in 5%-29% of cases)
Macrocephaly	Occasional (present in 5%-29% of cases)
Macroorchidism	Occasional (present in 5%-29% of cases)
Neoplasm of the breast	Occasional (present in 5%-29% of cases)
Neoplasm of the thyroid gland	Occasional (present in 5%-29% of cases)
Open bite	Occasional (present in 5%-29% of cases)
Optic atrophy	Occasional (present in 5%-29% of cases)
Polycystic ovaries	Occasional (present in 5%-29% of cases)
Prolonged bleeding time	Occasional (present in 5%-29% of cases)
Sarcoma	Occasional (present in 5%-29% of cases)
Tall stature	Occasional (present in 5%-29% of cases)
Testicular neoplasm	Occasional (present in 5%-29% of cases)
Blindness	-
Craniofacial hyperostosis	-
Facial asymmetry	-
Growth hormone excess	-
Hearing impairment	-
Intestinal polyposis	-
Large cafe-au-lait macules with irregular margins	-
Pathologic fracture	-
Phenotypic variability	-
Pituitary adenoma	-
Polyostotic fibrous dysplasia	-
Prolactin excess	-
Somatic mosaicism	-

Last updated: 10/1/2017

Cause Cause

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.^[5]^[7]

Last updated: 9/9/2016

Inheritance Inheritance

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.^[5]^[6]

Because mutations that cause MAS are acquired, a person with MAS does not pass the disorder on to children.

Last updated: 9/9/2016

Diagnosis Diagnosis

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:^[1]

Café-au-lait skin spots with characteristic features (jagged, irregular borders; distribution respecting the midline of the body; and following the developmental lines of Blaschko)
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)

MAS may be suspected at birth based upon identifying the characteristic cafe-au-lait spots. However, in many cases, it may not be suspected until late infancy or childhood when precocious (very early) puberty develops or when bone deformities become obvious.^[3]

Last updated: 8/28/2017

Treatment Treatment

Management of McCune-Albright syndrome (MAS) is most effective with a multidisciplinary team of specialists including orthopedists and endocrinologists. Although there is no cure for MAS, drug treatments or surgery may help some of the endocrine symptoms, and surgery may help to manage bone problems that cause visual disturbance, severe pain, or severe disfigurement.^[4]^[6] Generally, treatment depends on what tissues are affected as well as the severity.^[2]

Bisphosphonates are frequently used to treat fibrous dysplasia. Strengthening exercises are recommended to help maintain strength around the bones and minimize the risk of fractures.^[2]^[6]

More detailed information about the management of MAS is available on Medscape Reference's website.

Last updated: 9/9/2016

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Prognosis Prognosis

The long-term outlook (prognosis) for people with McCune-Albright syndrome (MAS) varies depending on the symptoms and severity in each affected person. Medical therapies can improve or control endocrine symptoms in most people with MAS.^[1]

Fibrous dysplasia is progressive throughout childhood and adolescence, and typically plateaus in middle and late adulthood. In some people, small amounts of fibrous dysplasia may cause few or no symptoms. In others, extensive bone disease may cause significant problems including loss of mobility, progressive scoliosis, facial deformity, and loss of vision and/or hearing.^[1]

Apart from the small proportion of people with increased surgery-related mortality and those who develop cancer, MAS is not associated with a significantly increased risk of death. In general, people with MAS have a normal life span.^[8]

Last updated: 9/9/2016

Statistics Statistics

McCune-Albright syndrome (MAS) is estimated to occur in 1 in 100,000 to 1 in 1 million people, making it a very rare disorder.^[8]

Last updated: 9/9/2016

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied McCune-Albright syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

The Fibrous Dysplasia Foundation has established the FD/MAS Patient Registry. Not only will the Registry provide valuable information for families and doctors to make the best care decisions possible, it will be important to help researchers decide what are the most important challenges to address. The Registry will also help scientists find out if there are any FD / MAS patients who might be a good match for their research studies.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Fibrous Dysplasia Foundation, Inc.
1380 Monroe St., NW #420
Washington, DC 20010
E-mail: info@fibrousdysplasia.org
Website: http://www.fibrousdysplasia.org
The MAGIC Foundation
4200 Cantera Dr. #106
Warrenville, IL 60555
Toll-free: 800-362-4423
Telephone: 630-836-8200
Fax: 630-836-8181
E-mail: contactus@magicfoundation.org
Website: https://www.magicfoundation.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Healthcare Resources

The Fibrous Dysplasia Foundation has a searchable database of clinicians with experience treating fibrous dysplasia, McCune-Albright syndrome and cherubism. Each clinician is individually reviewed by their Medical Advisory Council.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) provides information related to the health of children, adults, and families. Click on the link to view information on this topic.
Genetics Home Reference (GHR) contains information on McCune-Albright syndrome. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
MeSH® (Medical Subject Headings) is a terminology tool used by the National Library of Medicine. Click on the link to view information on this topic.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss McCune-Albright syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

Don’t Miss the NCATS Toolkit for Patient-Focused Therapy Development Event
August 31, 2017
2017 Million Dollar Bike Ride Pilot Grant Program
August 30, 2017
Funding Opportunities Now Available for the Undiagnosed Diseases Network (UDN) Phase II
August 30, 2017
IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017
2016 Million Dollar Bike Ride Pilot Grant Program
August 15, 2016
Young Investigator Initiative Career Development and Grant Mentoring Program
June 21, 2016

NCATS Co-Sponsored Conferences

International Meeting on Fibrous Dysplasia of Bone/McCune-Albright Syndrome: Best Clinical Practice and Future Research Sunday, October 3, 2010 - Tuesday, October 5, 2010
Location: NIH, Natcher Conference Center, Bethesda, Maryland
Description: The clinical scientists presented the results of their investigations and experience in the care of patients with fibrous dysplasia (FD) to the entire group for discussion and comment. At the end of the conference they came together in subgroups to define what is commonly held to be the best clinical practice. The scientists likewise presented their data for discussion and comment and came together to generate a roadmap for the focus of current and future research. It was also a goal to create greater collaboration between and among the clinical and basic scientists and the patient advocacy groups. One goal of the latter interaction was to promote the creation of a patient registry and tissue bank that will allow for the collection of standardized data on an international basis and make invaluable clinical material available to basic scientists.

Contact: Michael T. Collins, MD, mc247k@nih.gov mc247k@nih.gov

Co-funding Institute(s): National Institute of Dental and Craniofacial Research, Office of Rare Diseases Research
- Agenda ( - 144KB)
- Speakers ( - 87KB)
- Summary ( - 58KB)

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

My daughter who is 3 months old has a large cafe-au-lait lesion that has darkened since birth. It is very classical for this syndome (midline, coast of Maine, covers entire right buttocks and back of leg). We were referred to a pediatric dermatologist and she is being worked up for McCune Albright. The next step is a full series of x-rays. They are not sure taking them this early would show any bony changes. Do you have any recommendations of steps we can take now to determine if she does indeed have this syndrome and to what degree she is affected? See answer
What is the life expectancy? See answer
I was diagnosed with McCune Albright when I was 16. I was wondering the risks of pregnancy with McCune Albright? I am 20 now and already had 1 miscarriage. I want to know if this is possibly from my syndrome? See answer
Is McCune-Albright syndrome picked up by amniocentesis? I had an amniocentesis with my daughter and nobody told me she had it. See answer
Can you please provide some general information about McCune-Albright syndrome? See answer

Have a question? Contact a GARD Information Specialist.

References References

Alison M Boyce and Michael T Collins. Fibrous Dysplasia/McCune-Albright Syndrome. GeneReviews. February 26, 2015; http://www.ncbi.nlm.nih.gov/books/NBK274564/.
Michael Collins and Claudia Dumitrescu. McCune-Albright syndrome. Orphanet. May, 2008; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=562.
Sims EK. McCune Albright Syndrome. National Organization for Rare Disorders (NORD). December 22 2016; https://rarediseases.org/rare-diseases/mccune-albright-syndrome/.
McCune-Albright Syndrome. National Institute of Child Health and Human Development (NICHD). 2013; http://www.nichd.nih.gov/health/topics/mccune-albright/Pages/default.aspx.
McCune-Albright syndrome. Genetics Home Reference (GHR). January 2009; https://ghr.nlm.nih.gov/condition/mccune-albright-syndrome.
McCune-Albright syndrome. MedlinePlus. September 11, 2014; http://www.nlm.nih.gov/medlineplus/ency/article/001217.htm.
GNAS Complex Locus. Online Mendelian Inheritance in Man – OMIM web site. September 29, 2014; http://omim.org/entry/139320.
Gabriel I Uwaifo. McCune-Albright Syndrome. Medscape Reference. January 13, 2015; http://emedicine.medscape.com/article/127233-overview#a5.