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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
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Summary Summary


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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] Endocrinous features may include  precocious puberty especially in girls (resulting of estrogen excess from ovarian cysts),  excess growth hormone;  thyroid lesions with possible hyperthyroidism;  renal phosphate wasting, and, rarely, Cushing syndrome caused by an excess of the hormone cortisol produced by the adrenal glands, which are small glands located on top of each kidney.[1][2] MAS is not inherited.[1] MAS 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: 3/22/2018

Symptoms Symptoms


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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] Precocious puberty in boys with MAS occurs less frequently and later in life when compared to girls, and presents with penile growth and testes enlargement.[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: 3/22/2018

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 56 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal endocrine physiology 0031072
Large cafe-au-lait macules with irregular margins 0005605
Ovarian cyst 0000138
Precocious puberty
Early onset of puberty
Early puberty
[ more ]
0000826
30%-79% of people have these symptoms
Abnormality of facial skeleton
Anomaly of facial skeleton
0011821
Abnormality of femur morphology
Abnormality of the thighbone
0002823
Abnormality of the skull base 0002693
Accelerated skeletal maturation
Advanced bone age
Early bone maturation
[ more ]
0005616
Growth abnormality
Abnormal growth
Growth issue
[ more ]
0001507
Hyperthyroidism
Overactive thyroid
0000836
Increased serum testosterone level 0030088
Macroorchidism
Large testis
0000053
Monostotic fibrous dysplasia 0010736
Renal tubular dysfunction
Abnormal function of filtrating structures in kidney
0000124
Scoliosis 0002650
5%-29% of people have these symptoms
Benign gastrointestinal tract tumors
Non-cancerous GI tumors
0006719
Bone fracture 0020110
Bone pain 0002653
Decreased fertility
Abnormal fertility
0000144
Dental malocclusion
Bad bite
Malalignment of upper and lower dental arches
Misalignment of upper and lower dental arches
[ more ]
0000689
Facial asymmetry
Asymmetry of face
Crooked face
Unsymmetrical face
[ more ]
0000324
Gastroesophageal reflux
Acid reflux
Acid reflux disease
Heartburn
[ more ]
0002020
Goiter
Enlarged thyroid gland in neck
0000853
Growth hormone excess 0000845
Hearing impairment
Deafness
Hearing defect
[ more ]
0000365
Hepatocellular adenoma 0012028
Hyperplasia of the Leydig cells 0010791
Inappropriate sexual behavior 0008768
Increased circulating prolactin concentration 0000870
Irregular menstruation
Menstrual irregularity
0000858
Nasal obstruction
Blockage of nose
Nasal blockage
Obstruction of nose
Stuffy nose
[ more ]
0001742
Osteomalacia
Softening of the bones
0002749
Pancreatitis
Pancreatic inflammation
0001733
Paresthesia
Pins and needles feeling
Tingling
[ more ]
0003401
Polyostotic fibrous dysplasia 0010735
Recurrent fractures
Increased fracture rate
Increased fractures
Multiple fractures
Multiple spontaneous fractures
Varying degree of multiple fractures
[ more ]
0002757
Renal phosphate wasting 0000117
1%-4% of people have these symptoms
Aneurysmal bone cyst 0012063
Bone marrow hypocellularity
Bone marrow failure
0005528
Breast carcinoma
Breast cancer
0003002
Cholestasis
Slowed or blocked flow of bile from liver
0001396
Cutaneous myxoma 0030428
Hepatitis
Liver inflammation
0012115
Hyperphosphaturia
High urine phosphate levels
0003109
Hypophosphatemia
Low blood phosphate level
0002148
Pancytopenia
Low blood cell count
0001876
Primary hypercortisolism 0001579
Visual loss
Loss of vision
Vision loss
[ more ]
0000572
Percent of people who have these symptoms is not available through HPO
Blindness 0000618
Craniofacial hyperostosis
Excessive bone growth of the skull and face
0004493
Hyperparathyroidism
Elevated blood parathyroid hormone level
0000843
Increased circulating cortisol level 0003118
Intestinal polyposis 0200008
Pathologic fracture
Spontaneous fracture
0002756
Pituitary adenoma
Noncancerous tumor in pituitary gland
0002893
Somatic mosaicism 0001442
Showing of 56 |
Do you have more information about symptoms of this disease? We want to hear from you.
Last updated: 2/1/2021

Cause Cause


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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]

Precocious puberty in McCune-Albright syndrome is gonadotropin-independent. This means that it is not caused by early release of gonadotropins (luteinizing hormone and follicle-stimulating hormone), but, instead, the cause is the early secretion of high levels of sex hormones (male androgens and female estrogens). Precocious puberty caused by this condition is much more common in girls than in boys, resulting from an excess of estrogen produced by cysts in the ovaries.[5][1]

Other endocrine problems that may also occur in people with McCune-Albright syndrome are hyperthyroidism, acromegaly and Cushing syndrome. The hyperthyroidism in the MAS is caused by an enlarged thyroid gland (goiter) or by thyroid masses called nodules. Acromegaly results from an excess of growth hormone produced by the pituitary gland (a structure at the base of the brain that makes several hormones).  Cushing syndrome results from an excess of the hormone cortisol produced by the adrenal glands.[5]
Last updated: 3/22/2018

Inheritance Inheritance


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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: 3/22/2018

Diagnosis Diagnosis


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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 fibrous 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]

In cases when only one bone has fibrous dysplasia and there are not other symptoms  genetic testing is needed to establish the diagnosis.[1]

Last updated: 3/22/2018

Treatment Treatment


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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: 3/22/2018

Prognosis Prognosis


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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: 3/22/2018

Statistics Statistics


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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 disease? We want to hear from you.

Find a Specialist Find a Specialist


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If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

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.
  • 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 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 MedlinePlus Genetics.

Related Diseases Related Diseases


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Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm (see these terms).
Visit the Orphanet disease page for more information.

Research Research


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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 related to 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

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with McCune-Albright syndrome. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for McCune-Albright syndrome:
    The Fibrous Dysplasia/McCune-Albright Syndrome Patient Registry
     

Organizations Organizations


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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

  • FD/MAS Alliance
    2885 Sanford Ave. SW #40754
    Grandville, MI 49418
    Website: https://fdmasalliance.org/
    contact form: https://fdmasalliance.org/contact-us/
  • 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? We want to hear from you.

Learn More Learn More


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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. 
  • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
  • MedlinePlus Genetics contains information on McCune-Albright syndrome. This website is maintained by the National Library of Medicine.
  • 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

  • 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.
  • 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


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News

  • Rare Disease Day at NIH 2021
    March 1, 2021

GARD Answers GARD Answers


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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


  1. Boyce AM & Collins MT. Fibrous Dysplasia/McCune-Albright Syndrome. GeneReviews. February 26, 2015; http://www.ncbi.nlm.nih.gov/books/NBK274564/.
  2. 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.
  3. Sims EK. McCune Albright Syndrome. National Organization for Rare Disorders (NORD). December 22 2016; https://rarediseases.org/rare-diseases/mccune-albright-syndrome/.
  4. 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.
  5. McCune-Albright syndrome. MedlinePlus Genetics. January 2009; https://ghr.nlm.nih.gov/condition/mccune-albright-syndrome.
  6. McCune-Albright syndrome. MedlinePlus. September 11, 2014; http://www.nlm.nih.gov/medlineplus/ency/article/001217.htm.
  7. GNAS Complex Locus. Online Mendelian Inheritance in Man – OMIM web site. September 29, 2014; http://omim.org/entry/139320.
  8. Gabriel I Uwaifo. McCune-Albright Syndrome. Medscape Reference. January 13, 2015; http://emedicine.medscape.com/article/127233-overview#a5.
Do you know of a review article? We want to hear from you.
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