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Disease Profile

McCune-Albright syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

1-9 / 1 000 000

US Estimated

Europe Estimated

Age of onset

Childhood

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ICD-10

Q78.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease.

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype.

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder.

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

MAS; Albright syndrome; Albright's disease;

Categories

Congenital and Genetic Diseases; Endocrine Diseases; Female Reproductive Diseases;

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] 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]

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] 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]

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.

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

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]

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]

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 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]

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.

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

    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

      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.

        References

        1. Boyce AM & Collins MT. Fibrous Dysplasia/McCune-Albright Syndrome. GeneReviews. February 26, 2015; https://www.ncbi.nlm.nih.gov/books/NBK274564/.
        2. Michael Collins and Claudia Dumitrescu. McCune-Albright syndrome. Orphanet. May, 2008; https://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; https://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; https://www.nlm.nih.gov/medlineplus/ency/article/001217.htm.
        7. GNAS Complex Locus. Online Mendelian Inheritance in Man – OMIM web site. September 29, 2014; https://omim.org/entry/139320.
        8. Gabriel I Uwaifo. McCune-Albright Syndrome. Medscape Reference. January 13, 2015; https://emedicine.medscape.com/article/127233-overview#a5.

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