McCune Albright Syndrome - Causes, Symptoms, and Treatment

Introduction:

McCune Albright syndrome (MAS) is a rare, complex genetic condition characterized by cafe-au-lait spots (hyperpigmented lesions that may be light brown to dark brown), scar-like tissue formation of the bones (fibrous dysplasia), and precocious puberty. This condition affects the skin, bones, and certain endocrine glands. The diagnosis of the condition includes various blood examinations, imaging tests, genetic testing to evaluate genetic mutation, etc. The treatment modality for MAS involves hormone therapies and symptomatic relief. This condition is also known as Albright syndrome, osteitis fibrosa disseminata, polyostotic fibrous dysplasia, etc.

What Is McCune Albright Syndrome (MAS)?

McCune Albright syndrome (MAS) is a rare and complex genetic disorder affecting children's bones, skin, and endocrine systems. MAS results in classic café-au-lait spots (hyperpigmented lesions that may be light brown to dark brown), polyostotic fibrous dysplasia (abnormal scar-like tissue formation on bones), and functional impairment of certain endocrine glands. MAS is a mosaic disease (a condition in which an organism has more than one genetic line) occurring due to genetic mutation. Fibrous dysplasia occurring in MAS causes the replacement of bone with fibrous tissues, which may lead to fracture of the bone, uneven growth of the bones, and deformities. These fibrous lesions in the bone can become cancerous in about one percent of people with MAS.

Who Is Affected by McCune Albright Syndrome?

MAS affects children, and it can affect any child because it occurs due to a new genetic mutation. It has no gender variation and affects males and females equally.

Is McCune Albright Syndrome a Common Disease?

MAS is a rare and complex genetic disease, and it is estimated to occur in one in 1,00,000 to one in 10,00,000 individuals globally. However, the exact frequency of the MAS cannot be determined because a vast number of cases go undiagnosed and unreported.

What Causes McCune Albright Syndrome?

MAS occurs due to mutation in the GNAS1 gene (guanine nucleotide-binding protein). This mutation occurs shortly after the fertilization of the embryo. This condition is not hereditary; therefore, it is not passed down from generation to generation—the genetic mutation results from a change in the DNA (deoxyribonucleic acid) that happens after conception. The GNAS1 gene is responsible for producing a protein that regulates hormone production. The gene mutation causes the adenylate cyclase enzyme overproduction of hormones, which results in the classic MAS symptoms. Improper differentiation of osteoblasts (bone-forming cells) also occurs due to mutation of the GNAS1 gene, which is responsible for developing fibrous dysplasia in the affected individual.

What Is the McCune Albright Syndrome Triad?

Three symptoms of MAS constitute the McCune Albright syndrome:

1. Café-au-lait skin spots. Brown-colored pigmentation of the skin.

2. Fibrous dysplasia. Abnormal scar-like tissue formation in the bone.

3. Precocious puberty. A condition in which a child's body begins to change into that of an adult before the average age of puberty.

What Are the Symptoms of McCune Albright Syndrome?

The degree of severity and appearance of the symptoms of MAS are highly variable. Some children are born with bone abnormalities and increased hormone production by the endocrine glands. At the same time, some affected children show no variations in skin or bone and do not undergo precocious puberty as well. MAS primarily affects skin, bones, and certain endocrine glands; therefore, the symptoms of the condition are:

• Bone: The most common condition that affects the bones in MAS is fibrous dysplasia or polyostotic fibrous dysplasia. In fibrous dysplasia, the normal bone is replaced by abnormal scar-like fibrous connective tissues. This fibrous bone makes the bone weak, fragile, and extremely susceptible to fractures. Fibrous dysplasia often affects only one side of the body, but it may sometimes occur in different parts of the body. In rare cases, this fibrous bone can become cancerous. Symptoms occurring due to fibrous dysplasia are:

1. Bones of the face and skull grow asymmetrically.

2. Pain and discomfort in the affected bones.

3. Inability to move.

4. Scoliosis (abnormal lateral curvature of the spinal bone).

5. Rickets (softening and weakening of bones in children).

6. Osteomalacia (weakening of bone in both children and adults).

7. Short height and stature due to abnormal bone growth.

8. Uneven bone growth of the limbs leads to walking with a limp.

9. Frequent fractures.

10. Long bones become bowed.

11. Fibrous dysplasia of the craniofacial region can cause uneven jaw growth, nasal congestion, misaligned teeth, facial asymmetry, etc.

12. Protruding eyes and bulging forehead.

13. Neurological symptoms like loss of vision and loss of hearing due to compression of vital nerves and vessels from abnormal tissue development. However, this rarely occurs.

• Skin: Several individuals affected by MAS have cafe-au-lait spots, which are abnormal skin patches of brown-colored pigmentation that are irregularly shaped and have a jagged (rough with sharp points) border around them. These spots may be present at birth or develop soon after birth and become more visible with age. These spots may be present on only one side of the body.

• Endocrine Dysfunction: MAS affects the endocrine system of the patient in various ways:

1. The most significant symptom of endocrine dysfunction in MAS is precocious puberty. This is defined as the abnormally early onset of puberty because the glands responsible for the production of sex hormones become active at an abnormally early age. Secondary sexual characters start appearing at a very early age. Precocious puberty is more common in girls.

2. Hyperthyroidism occurs in about one-third of all MAS-affected populations. The symptoms of hyperthyroidism include anxiety, unusual weight loss, profuse sweating, fatigue, heat intolerance, etc.

3. Excess growth hormone leads to increased growth velocity in children affected by MAS. This excess of growth hormone occurs due to dysfunction of the pituitary gland. Children may also develop acromegaly (a hormonal disorder that causes enlargement of bones of the face, hands, and feet) due to excess growth hormone.

4. Adrenal dysfunction may lead to a condition known as Cushing’s syndrome. It is a syndrome characterized by excess cortisol in the body leading to increased weight in the upper part of the body, round face, swelling, easy bruising, pink-purple striations, etc.

How Is McCune Albright Syndrome Diagnosed?

The diagnosis of MAS can be made on the following grounds:

• Various classical signs and symptoms may be present at birth, like cafe-au-lait spots.

• Genetic testing can be done to check for mutation of the GNAS1 gene. This will provide a definitive diagnosis.

• Blood examinations may be done to check for endocrine dysfunction. In the case of MAS, there will be increased levels of growth hormone, cortisol, and thyroid hormones in the body.

• Multiple imaging tests like X-rays, CT scans (computed tomography), bone scans, etc., may be done to examine the bone growth, bone structure, and any other abnormalities in the bone. The fibrous-like tissues are also examined through imaging tests.

How Is McCune Albright Syndrome Treated?

The treatment of MAS depends upon the severity of the disease. The approach to treating MAS should be multidisciplinary. The treatment modalities for MAS include:

• Drugs and medications may be given to treat abnormal bone growth and reduce the risk of fractures. Drugs like Bisphosphonates may be given.

• Aromatase inhibitors may be given to treat precocious puberty.

• Antithyroid drugs may be used to treat hyperthyroidism caused due to overproduction of thyroid hormones.

• Physical and psychological support should be given to treat mobility issues.

• Surgery may be required in certain cases with fibrous dysplasia. Surgery may also be required in cases where these abnormal bones become cancerous.

Can McCune Albright Syndrome Be Prevented?

Unfortunately, MAS can not be prevented because it is a genetic condition occurring due to mutation in the GNAS1 gene. Genetic mutations occur sporadically, and they cannot be prevented from happening.

What Is the Life Expectancy With McCune Albright Syndrome?

The prognosis of MAS depends upon the severity of the condition and the symptoms. People affected by MAS are believed to have a normal life span, just like people who are not affected by this condition. However, a small percentage of people with the cancerous transformation of fibrous bone may require surgery and ultimately have surgery-related mortality. In general, MAS is not related to an increased risk of death.

Conclusion:

McCune Albright syndrome is a rare condition affecting children occurring due to genetic mutation. The prognosis of the disease depends upon the severity of the symptoms. However, doctors should work closely with the affected child to provide symptomatic relief and treat discomfort. It is highly recommended to see an expert physician when symptoms that are similar to that of MAS are seen. This condition is rare yet curable, and if treated with proper therapies, it can eventually lead to a normal life.