McCune–Albright syndrome

From WikiMD's Wellness Encyclopedia

(Redirected from McCune-Albright Syndrome)

McCune-Albright syndrome
   
ICD-10 Q78.1
ICD-9 756.54
DiseasesDB 7880
MedlinePlus 001217
eMedicine ped 1386
MeSH ID D005359

Alternate names[edit | edit source]

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

Defintion[edit | edit source]

McCune–Albright syndrome, or simply Albright syndrome, described in 1937 by Donovan James McCune and Fuller Albright,[1][2][3] is a genetic disorder of bones, skin pigmentation and hormonal problems along with premature puberty.

Epidemiology[edit | edit source]

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.

Presentation[edit | edit source]

McCune–Albright syndrome is suspected when two of the three following features are present:

Within the syndrome there are bone fractures and deformity of the legs, arms and skull, different pigment patches on the skin, and early puberty with increased rate of growth.

Approximately 20-30% of fibrous dysplasias are polyostotic, which means fibrous dysplasia and sclerotic bone are present in multiple sites; two thirds of patients are polyostotic before the age of ten. The disease frequently involves the skull and facial bones, pelvis, spine and shoulder girdle. The sites of involvement are the femur (91%), tibia (81%), pelvis (78%), ribs, skull and facial bones (50%), upper extremities, lumbar spine, clavicle, and cervical spine, in decreasing order of frequency. The craniofacial pattern of the disease occurs in 50% of patients with the polyostotic form of fibrous dysplasia.

Increased production of hormones by glands regulated by the G protein system is due to a mutation in the gene causing continuous activation of stimulatory G protein. This results in the so called "autonomous production" of hormones, including thyroid hormone, cortisol, estrogen and growth hormone. Therefore, hyperthyroidism, Cushing syndrome, precocious puberty in women with premature thelarche (breast growth), premature menarche (beginning of menstrual function), increased speed of growth and growth hormone excess can ensue. Increased serum estrogen concentrations correlate with large ovarian cysts. Ovarian cysts appear and disappear with changing estrogen concentrations, causing menstrual bleeding when estrogen decreases.

McCune–Albright syndrome has different levels of severity. For example, one child with McCune–Albright syndrome may be entirely healthy, with no outward evidence of bone or endocrine problems, enter puberty at close to the normal age, and have no unusual skin pigmentation. Diagnosis may be made only after decades. In other cases, children are diagnosed in early infancy, show obvious bone disease, and obvious increased endocrine secretions from several glands.

Cause[edit | edit source]

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.

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. 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.

Inheritance[edit | edit source]

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

Diagnosis[edit | edit source]

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 (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.

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

Treatment[edit | edit source]

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. Generally, treatment depends on what tissues are affected as well as the severity.

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.

Prognosis[edit | edit source]

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.

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.

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.


Notable cases[edit | edit source]

Mauricio Saravia, a Uruguayan artist with the disease

The disease made headlines in December, 2005 when a Haitian teen afflicted with the disease, Marlie Casseus, underwent a 17-hour emergency surgical procedure to remove a 7 kg (16 pound) tumour-like growth of bone from her face. A series of operations at Holtz Children's Hospital in Miami, Florida restored the child's face to a more normal proportion.[4]

See also[edit | edit source]

References[edit | edit source]

  1. synd/1844 at Who Named It?
  2. "Marlie Casseus". Archived from the original on 2007-05-29. Retrieved 2007-07-14.


External links[edit | edit source]


Pediatric glossary of terms | Glossary of medical terms | Dictionary of pediatrics


Health Topics > A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z
View All Health Topics in one page! | Health Encyclopedia | Index of health articles

Professions:Medicine | Nursing | Pharmacy | Healthcare science | Dentistry | Allied health professions | Healthcare

Medicine - Specialties and subspecialties
Surgery

Cardiac surgery - Cardiothoracic surgery - Colorectal surgery - Ophthalmology - General surgery - Neurosurgery - Oral and maxillofacial surgery - Orthopedic surgery - Hand surgery - Otolaryngology - ENT - Pediatric surgery - Plastic surgery - Reproductive surgery - Surgical oncology - Transplant surgery - Trauma surgery - Urology - Andrology - Vascular surgery

Medicine Internal medicine - Allergy / Immunology - Angiology - Cardiology - Endocrinology - Gastroenterology - Hepatology - Geriatrics - Hematology - Hospital medicine - Infectious disease - Nephrology - Oncology - Pulmonology - Rheumatology
Obstetrics and gynaecology Gynaecology - Gynecologic oncology - Maternal–fetal medicine - Obstetrics - Reproductive endocrinology and infertility - Urogynecology
Diagnostic Radiology - Interventional radiology - Nuclear medicine - Pathology - Anatomical - Clinical pathology - Clinical chemistry - Cytopathology - Medical microbiology - Transfusion medicine
Other specialties Addiction medicine - Adolescent medicine - Anesthesiology - Dermatology - Disaster medicine - Diving medicine - Emergency medicine - Family medicine - General practice - Hospital medicine - Intensive care medicine - Medical genetics - Narcology - Neurology - Clinical neurophysiology - Occupational medicine - Ophthalmology - Oral medicine - Pain management - Palliative care - Pediatrics - Neonatology - Physical medicine and rehabilitation (PM&R) - Preventive medicine - Psychiatry -Addiction psychiatry - Radiation oncology - Reproductive medicine - Sexual medicine - Sleep medicine - Sports medicine - Transplantation medicine - Tropical medicine - Travel medicine - Venereology
Medical education Medical school - USMLE - Bachelor of Medicine, Bachelor of Surgery - Bachelor of Medical Sciences - Doctor of Medicine - Doctor of Osteopathic Medicine - Alternative medicine - Allied health - Dentistry - Podiatry - Pharmacy - Physiotherapy - Molecular oncology - Nanomedicine - Personalized medicine - Public health - Rural health - Therapy - Traditional medicine - Veterinary medicine - Physician - Chief physician - History of medicine
Misc. topics Health topics A-Z - Rare diseases - Drugs - Diet - Medicine portal - First Aid - Glossary of medicine - Health insurance - Glossary of health topics - Drug classes - Medicines - List-Class medicine articles - Dentistry portal - Pharmacology and Medications-Medications portal - Pharmacology portal - Psychiatry portal
WikiMD
Navigation: Wellness - Encyclopedia - Health topics - Disease Index‏‎ - Drugs - World Directory - Gray's Anatomy - Keto diet - Recipes

Search WikiMD

Ad.Tired of being Overweight? Try W8MD's physician weight loss program.
Semaglutide (Ozempic / Wegovy and Tirzepatide (Mounjaro / Zepbound) available.
Advertise on WikiMD

WikiMD's Wellness Encyclopedia

Let Food Be Thy Medicine
Medicine Thy Food - Hippocrates

Medical Disclaimer: WikiMD is not a substitute for professional medical advice. The information on WikiMD is provided as an information resource only, may be incorrect, outdated or misleading, and is not to be used or relied on for any diagnostic or treatment purposes. Please consult your health care provider before making any healthcare decisions or for guidance about a specific medical condition. WikiMD expressly disclaims responsibility, and shall have no liability, for any damages, loss, injury, or liability whatsoever suffered as a result of your reliance on the information contained in this site. By visiting this site you agree to the foregoing terms and conditions, which may from time to time be changed or supplemented by WikiMD. If you do not agree to the foregoing terms and conditions, you should not enter or use this site. See full disclaimer.
Credits:Most images are courtesy of Wikimedia commons, and templates Wikipedia, licensed under CC BY SA or similar.

Contributors: Prab R. Tumpati, MD