Albright’s Disease (McCune-Albright Syndrome)

Albright’s disease, medically known as McCune-Albright syndrome, is a rare genetic condition that affects bones, skin, and the hormonal system, causing a unique combination of symptoms that vary widely from person to person.

McCune-Albright syndrome, MAS, Polyostotic fibrous dysplasia, Fibrous dysplasia/McCune-Albright syndrome, FD/MAS

Table of contents

• What is Albright’s Disease?
• What Causes This Condition?
• How Common Is It?
• Symptoms and Signs
• Possible Complications
• How Is It Diagnosed?
• Treatment Options
• Outlook and Life Expectancy

What is Albright’s Disease?

Albright’s disease is a complex disorder that affects multiple parts of the body. It was first described in the 1930s by American doctors Donovan James McCune and Fuller Albright, which is why it’s also called McCune-Albright syndrome^[1]. The condition creates a pattern of problems involving bones, skin coloring, and the body’s hormone-producing glands^[2].

The classic signs include three main features. First, people develop areas of abnormal bone tissue called fibrous dysplasia, where normal bone is replaced by scar-like tissue^[1]. Second, they have distinctive skin markings called café-au-lait spots, which are light brown patches on the skin^[2]. Third, they may experience hormonal problems, most commonly early puberty in girls^[3].

Not everyone with Albright’s disease has all three features. The condition appears differently in each person because of how the underlying genetic problem spreads through the body during early development^[4]. Some people have mild symptoms that barely affect their daily life, while others face serious medical challenges^[2].

What Causes This Condition?

Albright’s disease is caused by a change in a gene called GNAS. This gene provides instructions for making a protein that helps cells communicate with each other and respond to hormones^[1]. When the gene has a mutation, the protein stays “turned on” all the time, causing cells to receive constant signals even when they shouldn’t^[4].

The mutation happens randomly very early in a baby’s development, shortly after conception. It occurs when cells are dividing and making copies of themselves during the first few weeks after a sperm fertilizes an egg^[2]. This means the mutation is not inherited from parents, and parents cannot pass it to their children^[3].

Because the mutation happens during development, not all cells in the body carry it. This creates a pattern called mosaicism, where some cells are normal and others have the mutation^[4]. The symptoms a person experiences depend on which tissues contain cells with the mutation and how many mutated cells are present in each tissue^[5].

How Common Is It?

Albright’s disease is very rare. It occurs in approximately 1 out of every 100,000 to 1,000,000 people worldwide^[1][2]. Because of its rarity, many doctors may never see a case during their entire career, which can sometimes make diagnosis challenging^[3].

The condition can affect anyone regardless of race or ethnic background. Both boys and girls can develop Albright’s disease, though certain symptoms like early puberty are much more common in girls^[6].

Symptoms and Signs

Bone Problems

The most significant bone problem in Albright’s disease is fibrous dysplasia. In this condition, normal bone tissue is replaced by fibrous, scar-like tissue that resembles the stringy fibers in a tendon^[1]. This abnormal tissue is weaker than normal bone and grows unevenly, creating several problems.

Bones affected by fibrous dysplasia break more easily than normal bones. Children may suffer fractures from minor falls that wouldn’t hurt other children^[2]. The bones of the face, skull, arms, and legs are most commonly affected^[3]. When skull and facial bones are involved, the face may grow unevenly on one side, creating an asymmetric appearance^[1].

If leg bones are affected and grow at different rates, one leg may become longer than the other, causing a limp^[2]. The abnormal bone areas often appear on just one side of the body^[3]. Some people also develop abnormal curvature of the spine, called scoliosis^[1].

People with fibrous dysplasia may experience ongoing bone pain and difficulty moving affected limbs^[2]. In rare cases, less than 1 percent of people, the abnormal bone tissue can become cancerous^[1].

Skin Changes

People with Albright’s disease typically have distinctive skin markings called café-au-lait spots. These are flat patches of skin that are light brown to dark brown in color, similar to coffee with milk, which is what “café-au-lait” means in French^[3].

What makes these spots special in Albright’s disease is their irregular, jagged borders, which doctors describe as looking like the “coast of Maine” with its rocky, uneven coastline^[1]. This is different from café-au-lait spots in other conditions, which have smooth, even borders like the “coast of California”^[1].

These skin markings are often present from birth or appear in the first weeks of life^[3]. Like the bone problems, the café-au-lait spots often appear only on one side of the body^[2]. They may become more noticeable as a child grows older^[2].

Hormonal Problems

Albright’s disease affects the endocrine system, which is the network of glands throughout the body that produce hormones. Hormones are chemical messengers that control many body functions including growth, metabolism, and sexual development^[2].

The most common hormonal problem is early puberty, especially in girls. Some girls begin having menstrual periods as early as age 2, long before other signs of puberty like breast development or pubic hair appear^[1]. This happens because cysts that form on the ovaries produce too much estrogen, the main female hormone^[1]. Early puberty is less common in boys but can occur^[6].

About half of people with Albright’s disease develop problems with their thyroid gland, a butterfly-shaped organ at the base of the neck. The thyroid may become enlarged, forming a visible swelling called a goiter, or develop lumps called nodules^[1]. Many produce too much thyroid hormone, a condition called hyperthyroidism, which causes a fast heartbeat, high blood pressure, weight loss, trembling hands, and excessive sweating^[1].

The pituitary gland, a pea-sized structure at the base of the brain, sometimes produces too much growth hormone. This can lead to acromegaly, where the hands, feet, and facial features become unusually large^[1]. Excess growth hormone can also make fibrous dysplasia in skull bones expand more rapidly, potentially affecting vision and hearing^[5].

Rarely, young children under age 2 may develop Cushing syndrome due to excess cortisol hormone from the adrenal glands^[1]. This causes weight gain in the face and upper body, slower growth, fragile skin, and fatigue^[3].

Other Problems

Some people with Albright’s disease develop non-cancerous growths in the digestive system called polyps^[1]. Boys may develop testicular abnormalities including enlarged testicles^[5]. Other less common problems can affect various organs and systems in the body^[1].

Possible Complications

Without proper management, Albright’s disease can lead to several complications. The weakened bones may break repeatedly, and some people develop brittle bones similar to osteoporosis^[3]. When skull bones are severely affected, they may press on nerves, potentially causing blindness or deafness^[3].

Children who experience early puberty tend to have a growth spurt earlier than other children, making them taller than their peers initially. However, their bones stop growing sooner, so they often end up shorter than average as adults^[6].

Abnormal bone growth can cause deformities that affect mobility and movement^[3]. Some people develop soft, cyst-prone bones in a condition called osteitis fibrosa cystica^[3]. The combination of bone problems and uneven growth can lead to physical disabilities^[3].

In very rare cases, excessive growth hormone can lead to gigantism, where the face, hands, and feet grow abnormally large^[3]. Adrenal gland problems may cause tumors to develop^[3].

How Is It Diagnosed?

Diagnosing Albright’s disease requires a combination of physical examination, medical history, and various tests. Doctors look for at least two of the three classic features: fibrous dysplasia, café-au-lait spots, and hormonal problems^[6].

During a physical exam, doctors check for the characteristic skin markings and look for signs of uneven bone growth or facial asymmetry^[3]. They assess whether a child is experiencing early signs of puberty and examine for signs of other hormonal imbalances^[3].

X-rays can show areas of fibrous dysplasia in bones, revealing the characteristic abnormal tissue that looks different from normal bone^[3]. More detailed imaging tests like CT scans or MRI scans may be done to better see the extent of bone involvement, especially in the skull^[4]. Ultrasound may be used to check for ovarian cysts in girls with early puberty^[3].

Blood tests check hormone levels to identify problems with the thyroid, pituitary, adrenal glands, or sex hormones^[3]. These tests may show high levels of thyroid hormone, growth hormone, estrogen, cortisol, or parathyroid hormone^[3]. Blood tests also measure calcium and phosphate levels, which may be abnormal in Albright’s disease^[4].

Genetic testing can identify the GNAS gene mutation responsible for the condition^[3]. However, because the mutation is present only in some cells, it may not always show up in blood samples. Sometimes a biopsy of affected tissue is needed to find the mutation^[4].

Treatment Options

There is currently no cure for Albright’s disease. Treatment focuses on managing symptoms and preventing complications^[3][11]. Because the condition affects multiple body systems, people with Albright’s disease need care from a team of specialists working together^[2].

Managing Bone Problems

Medications called bisphosphonates can help reduce bone pain and may slow the progression of fibrous dysplasia^[10]. These medications work by slowing down the breakdown of bone tissue^[1].

Surgery may be needed to repair broken bones, correct deformities, or remove painful areas of abnormal bone^[3][11]. Operations on the skull may be necessary if bone growth threatens vision or hearing^[11]. However, surgery must be carefully timed because abnormal bone tissue can grow back^[11].

Radiation therapy should be avoided when possible because it may increase the risk of the abnormal bone tissue becoming cancerous^[10].

Managing Hormonal Problems

Treatment for early puberty in girls with Albright’s disease is challenging. Unlike other forms of early puberty, it does not respond well to standard medications^[10]. Doctors may try medications called aromatase inhibitors that block estrogen production^[10][11].

Ovarian cysts usually go away on their own without treatment, so surgery to remove them is rarely needed^[8]. Early puberty in boys is less common and may be treated with medications to block sex hormone production^[11].

An overactive thyroid is treated with medications that reduce thyroid hormone production, or in some cases, surgery to remove part of the thyroid gland^[11]. Excess growth hormone may be treated with medications that block hormone production or with surgery to remove pituitary tumors^[10]. Cushing syndrome in young children may require surgery to remove the adrenal glands^[11].

Ongoing Care

People with Albright’s disease need regular monitoring throughout their lives. This includes periodic imaging tests to check bone involvement, blood tests to monitor hormone levels, and screenings for potential complications^[11].

Physical therapy may help maintain mobility and muscle strength^[11]. Some people need assistive devices like braces, crutches, or wheelchairs to help with movement^[2].

Outlook and Life Expectancy

With proper treatment and monitoring, people with Albright’s disease can have a relatively normal life expectancy^[2][3]. The outlook varies greatly depending on which parts of the body are affected and how severe the symptoms are^[3].

The severity of symptoms is difficult to predict and can range from very mild to quite severe^[3]. Some people with Albright’s disease live relatively normal lives with few limitations, while others face ongoing medical challenges and may require multiple surgeries throughout their lives^[2].

Women with Albright’s disease who experienced early puberty are often able to become pregnant and have healthy children as adults^[8]. Children who undergo early puberty will need support as they deal with physical and emotional changes at a younger age than their peers^[6].

Working with a team of experienced healthcare providers and maintaining regular follow-up care is essential for the best possible outcomes^[2][11].