McCune-Albright syndrome

McCune-Albright syndrome is a genetic condition that affects bone growth, skin pigmentation and the body’s hormone balance. Bones that break easily and premature sexual maturity are typical signs of the condition. There is currently no cure.

Symptoms range in severity#

In some cases the bone abnormalities and hormone problems are severe enough to be obvious in infancy. In other cases the child seems healthy in all respects. It is difficult to predict how severe the symptoms will be or how a child with McCune-Albright syndrome will be affected throughout life.

Signs and symptoms#

The signs and symptoms can include:

• polyostotic fibrous dysplasia – abnormal growth of two or more bones, most often the bones of the face, skull, arms and legs
• café au lait birthmarks – flat, oval-shaped spots with a jagged outline, usually on the abdomen or back
• premature sexual maturity – this can affect girls and boys, but is much more common in girls, and may include onset of the menstrual period before the growth of breasts or pubic hair
• ovarian cysts, which are thought to trigger early menstruation
• symptoms of an overactive thyroid gland (hyperthyroidism)

Café au lait birthmarks are often the first signs of the condition and appear at or shortly after birth. In people with lighter skin they look light brown, or ‘milk-coffee coloured’. In people with darker skin they may be harder to see.

Complications#

Some of the complications of McCune-Albright syndrome can include:

• brittle, warped bones (osteoporosis)
• repeated fractures
• rickets
• blindness or deafness due to abnormal growth of skull bones
• adrenal gland tumours
• osteitis fibrosa cystica – soft bones that are prone to developing cysts
• mobility problems or disability caused by abnormal bone growth or asymmetry of the skeleton
• in rare cases, excessive growth (gigantism) because of growth hormone imbalance, most often affecting the face and feet
• Cushing’s syndrome

Cushing’s syndrome#

Cortisol is a hormone made by the adrenal glands, which sit above the kidneys. McCune-Albright syndrome may cause enlargement of the adrenal glands and overproduction of cortisol. This leads to a range of symptoms known together as Cushing’s syndrome, which can include:

• arrested growth in childhood
• obesity and weight gain around the abdomen
• wasting of the limbs
• a hump of fat high on the back
• a round, red and puffy face
• thin, easily bruised skin
• slow healing of skin wounds and skin ulcers

What causes McCune-Albright syndrome?#

McCune-Albright syndrome is caused by a change in the GNAS1 gene that makes the gene more active than usual. The change is not inherited from the parents and is not present at the time of conception. Instead, it occurs during an early cell division in the developing embryo. As a result, the change is present in some, but not all, cells of the body. This is known as ‘mosaicism’.

Despite hormonal irregularities, most women with McCune-Albright syndrome are fertile. A person with the condition cannot pass it on to their children. The cause of the genetic change itself is not known.

Diagnosis#

Tests used to help diagnose McCune-Albright syndrome may include:

• medical history
• physical examination
• blood tests to check hormone levels of the thyroid, parathyroid, adrenal glands and pituitary gland
• x-rays to examine the skeleton
• a bone scan using an injection of radioactive material
• other scans, such as MRI
• genetic tests

Treatment#

There is no cure for McCune-Albright syndrome. Treatment depends on the person’s age, general health and the severity of their symptoms, and may include:

• medication to manage pain
• surgery to support affected bones with grafts, pins, casts or a combination of procedures
• treatment with medicines known as bisphosphonates to improve bone density
• vitamin D supplements to reduce the risk of rickets
• a regular, supervised exercise program to improve bone density
• physical therapy to maintain or improve joint mobility
• medication to reduce levels of the female sex hormone oestrogen
• surgery to remove ovarian cysts
• surgery to remove abnormal adrenal glands in the case of Cushing’s syndrome
• hormone therapy or surgery to treat gigantism or a pituitary tumour

Treatment team#

Specialist doctors involved in care may include an orthopaedic surgeon to treat bone problems, a plastic surgeon to treat facial deformities, and an endocrinologist to treat hormone imbalances.

Genetic counselling#

If your child has been diagnosed with McCune-Albright syndrome, it may help to speak to a genetic counsellor. Genetic counsellors are health professionals qualified in both counselling and genetics. As well as providing emotional support, they can help you understand McCune-Albright syndrome, what causes it, and what a diagnosis means for your child’s health and development. They are trained to provide information and support that is sensitive to your family’s circumstances, culture and beliefs, and can help connect you with support groups and other families affected by the condition.

Key points#

• McCune-Albright syndrome is a genetic condition affecting bone growth, skin pigmentation and hormone balance.
• Symptoms range in severity and are difficult to predict.
• In people with darker skin, café au lait birthmarks may be harder to see.
• The condition may cause enlargement of the adrenal glands and overproduction of cortisol, leading to Cushing’s syndrome.
• Cushing’s syndrome can cause arrested growth in childhood, among other symptoms.

Where to get help#