McCune-Albright syndrome

Background

McCune-Albright syndrome (MAS) is a rare condition that was first described in 1937. It is sometimes called Albright syndrome.

The classic presentation of this syndrome consists of 3 features:

Café-au-lait spots on the skin
Bone abnormalities
Endocrine (hormonal) abnormalities, in particular early puberty

At least 2 of these features need to be present to diagnose the condition. MAS is a genetic condition that is caused by a spontaneous (chance) mutation in the GNAS1 gene. The mutation occurs early in the development of an embryo and affects only a subset of the patient's cells (called mosaicism). The mutation cannot be passed on to affected patient's children.

Clinical features

1. Café-au-lait spots	These are flat coffee-coloured patches on the skin. Solitary café-au-lait spots are common in the general population; the presence of numerous spots is suggestive of a genetic disorder, such as type 1 neurofibromatosis or MAS. The café-au-lait spots of MAS may be present at birth or appear during childhood. They are most commonly found on the neck, lower back, or buttocks and are distributed along the lines of Blaschko. The spots may be small or large, have irregular borders, and are usually on the same side of the body as the bony lesions. Although spots occasionally appear on both sides of the body, individual patches do not usually cross the midline.
2. Bone abnormalities	The bone abnormality in MAS is called polyostotic fibrous dysplasia; normal bone is replaced by fibrous tissue and weakened bone. In many cases, bones on one side of the body only are affected. The bony abnormalities may cause recurrent fractures, bone pain, facial asymmetry, scoliosis (abnormal curvature of the spine), unequal leg length, limb bowing, or a limp. Generally, the bony changes progress until early adulthood and then become relatively stable.
3. Endocrine abnormalities	The most common endocrine abnormality in MAS is early puberty; the average age of onset is around 5 years. Girls are more commonly affected than boys. MAS is also associated with hyperthyroidism, growth hormone excess (acromegaly), Cushing syndrome, breast discharge due to excess prolactin hormone, and renal phosphate wasting (excess urinary excretion of phosphate, which may result low circulating phosphate in the blood).
4. Other associated problems	MAS has been associated with a variety of other clinical problems including: Developmental delay Liver disease and jaundice High blood pressure and abnormal heart rhythms

Café au lait macules

Diagnosis

X-rays of the affected bones show characteristic features such as a central ‘ground-glass’ pattern, lytic lesions (local disappearance of normal bone), cyst-like appearance, and evidence of current or past fractures.
CT, MRI, and nuclear medicine bone scanning may also be useful.
Once the condition has been diagnosed, other investigations are required to screen for occult (concealed) endocrine abnormalities.

Treatment

Medical treatment of MAS has had mixed success.
Early puberty can be treated with various hormonal agents, but results have been inconsistent.
A class of medications, called bisphosphonates, have recently been used to reduce fracture rates and bone pain in patients with MAS. However, results have again been inconsistent.
Other endocrine problems require specific medication or surgery.

Complications

Bony changes in the skull can result in damage to nerves causing vision and/or hearing loss.
Bony changes in the chest wall may lead to difficulty breathing.
A type of bone cancer called osteosarcoma develops in up to 2% of patients with MAS. This tumour is found most often in patients who have received radiation treatment to affected bone lesions.
Although 2 long-term studies have shown no increased risk of premature death, several authors have noted unexplained sudden death in patients with severe features of the disease.

Related information

References:

McCune-Albright Syndrome – eMedicine dermatology, pediatric diseases
Albright Syndrome – eMedicine pediatrics, general medicine
McCune-Albright Syndrome – eMedicine endocrinology
Dumitrescu CE, Collins MT. McCune-Albright syndrome. Orphanet J Rare Dis. 2008; 3: 12.
Roth JG, Esterly NB. McCune-Albright syndrome with multiple bilateral café au lait spots. Pediatr Dermatol. 1991 Mar;8(1):35-9.

On DermNet NZ:

Congenital melanocytic naevi (brown birthmarks)

Other websites:

McCune-Albright Syndrome – Medline Plus
McCune-Albright Syndrome – OMIM
McCune-Albright Syndrome – National Institute of Child Health and Human Development

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Author: Dr Marie Hartley, Staff Writer.