DiGeorge syndrome

Definition

DiGeorge syndrome is a disorder present at birth (congenital) caused by problems within a developing embryo that occur due to chromosome defects. The specific chromosome defect your baby has dictates the medical concerns he or she will face.

Doctors sometimes refer to DiGeorge syndrome as velocardiofacial syndrome because problems frequently associated with the disorder include cleft palate (velopharyngeal incompetence), cardiac defects and abnormal facial features. Other common problems include immune system defects and low blood-calcium levels.

There's no cure for DiGeorge syndrome, and the long-term outlook for children with DiGeorge syndrome varies widely, depending on the organs affected. Treatment of DiGeorge syndrome focuses on correcting or managing the medical problems caused by the chromosome defect.

Symptoms

Infants with DiGeorge syndrome often have distinct facial features, including:

• Wide-set eyes
• Low-set ears, with a notched ear fold
• Small jaw
• A narrow, short groove in the upper lip

Other signs and symptoms of DiGeorge syndrome include:

• Cleft palate
• Recurrent infections, such as chronic runny nose or multiple bouts of pneumonia, oral thrush (candidiasis), diaper rash or diarrhea
• Cramp-like spasms of the baby's hands and fingers, or twitches or spasms of the muscles in the baby's face, throat or arms (tetany)
• Developmental delays, most often speech delay
• Slow mental development
• Lack of appetite
• Poor weight gain
• Failure to thrive

Causes

The cause of DiGeorge syndrome is problems in the chromosomes within a baby's cells. Most babies born with DiGeorge syndrome are missing part of chromosome 22. Rarely, there may be other chromosome abnormalities that cause DiGeorge syndrome, such as a defect in chromosome 10. Sometimes babies with DiGeorge syndrome have no detectable chromosome abnormality.

Usually, the chromosome abnormalities related to DiGeorge syndrome aren't inherited. Instead, they happen spontaneously during embryonic development. The reason why these chromosome abnormalities occur isn't clear.

When portions of chromosome 22 are missing, it can affect the parts of the body the chromosome is responsible for developing, which include the following:

• Thymus gland. Part of your immune system, the thymus gland is a small organ located in your upper chest beneath your breastbone. During childhood, white blood cells called T lymphocytes (T cells) develop in the thymus and are distributed to your lymph nodes to help fight infection. After puberty, other parts of your body become more important in making and distributing T cells. As you grow, the thymus decreases in size and is slowly replaced by fat tissue. Defects in chromosome 22 may cause your baby's thymus gland to be smaller than normal (hypoplastic). In some cases, children with DiGeorge syndrome don't have a thymus gland.
• Parathyroid glands. You have four parathyroid glands in your neck, next to your thyroid gland. These small oval-shaped glands are each about the size of a pea. They maintain proper levels of calcium and phosphorus in your body by turning the secretion of parathyroid hormone (PTH) off or on. DiGeorge syndrome can be associated with parathyroid glands that are smaller than normal, which usually causes lower than normal secretion of PTH (hypoparathyroidism). Hypoparathyroidism often results in low levels of calcium (hypocalcemia) and high levels of phosphorus in the blood (hyperphosphatemia).
• Heart outflow vessels. Outflow vessels are the blood vessels that transport blood away from your heart. The largest is the aorta. Babies with DiGeorge syndrome frequently have heart defects associated with heart outflow vessels. The most common defects include: tetralogy of Fallot, ventricular septal defect, interrupted aortic arch, truncus arteriosus and patent ductus arteriosus In some infants, these defects may cause signs and symptoms such as shortness of breath, lack of appetite and poor weight gain.
• Facial features. Chromosome 22 is involved in the development of your facial bones, as well as your lips and ears. Defects in chromosome 22 cause the distinct facial features of DiGeorge syndrome. In some cases, the chromosome defects may also cause an opening or split in the roof of the mouth (cleft palate).

Your body's lymphatic system is part of your immune system, which protects you against infection and disease. It includes your spleen, thymus, bone marrow, lymph nodes and lymph channels, as well as your tonsils and adenoids.

The parathyroid glands, which lie behind the thyroid, manufacture the hormone parathyroid, which plays a role in regulating your body's level of the minerals calcium and phosphorus.

Risk factors

In most cases, researchers don't know what causes the chromosome abnormalities that result in DiGeorge syndrome. In a small percentage of cases, DiGeorge syndrome may be inherited from a parent, so a family history of the disease may increase a baby's risk of developing DiGeorge syndrome.

When to seek medical advice

Within the first 24 to 48 hours after they are born, babies who have DiGeorge syndrome often experience cramp-like spasms of their hands and fingers, or twitches or spasms of the muscles in their face, throat or arms (tetany). These spasms are a result of low blood-calcium (hypocalcemia) and high levels of phosphorus in their blood due to low levels of parathyroid hormone (hypoparathyroidism).

If you notice signs of tetany, or if your child has other signs or symptoms of DiGeorge syndrome, make an appointment to talk with your doctor.

Tests and diagnosis

DiGeorge syndrome may be difficult to definitively diagnose because the disorder can cause a wide variety of signs and symptoms, the severity and combination of which depend on the nature of your child's chromosome defect. One of the most telltale signs of DiGeorge syndrome is its distinct facial features.

If your baby's doctor suspects DiGeorge syndrome, he or she may recommend the following tests:

• Blood test. If your child has DiGeorge syndrome, a blood test may show low levels of calcium and high levels of phosphorus in the blood, as well as low levels of T cells.
• Chest X-ray. A chest X-ray may suggest a heart defect, requiring further tests or exams to confirm the diagnosis.
• Genetic studies. These tests may show chromosome defects related to DiGeorge syndrome.

Complications

Possible complications associated with DiGeorge syndrome are related to the specific medical problems caused by your child's chromosome defect.

Parathyroid glands
If your child's parathyroid glands aren't fully developed (hypoparathyroidism), he or she may have the following complications:

• Stunted growth (short stature)
• Slow mental development (or mental retardation)
• Cataracts

Thymus gland
If your child's thymus gland is underdeveloped or absent, severe infection may occur due to a lack of infection-fighting T cells.

Heart
If left untreated, heart defects can result in severe complications, such as:

• Congestive heart failure. Congestive heart failure is a condition in which the heart can't pump enough blood to meet the body's needs.
• Enlargement of the heart (cardiomegaly). Some heart defects cause increased blood flow through the heart, which forces it to work harder than normal, resulting in enlargement of the heart.
• High blood pressure in the lungs (pulmonary hypertension). Increased blood flow to the lungs as a result of a heart defect can cause the lungs' blood vessels to narrow, increasing blood pressure and making it increasingly difficult for the baby's heart to pump blood into the lungs.
• Endocarditis. Children with some types of heart defects are at increased risk of an infection of the heart (endocarditis).
• Stroke. Children with heart defects such as a hole between the heart's lower pumping chambers (ventricular septal defect) are at increased risk of a stroke due to a blood clot passing through the hole in the heart and going to the brain.

Treatments and drugs

Because there isn't a way to repair chromosome defects, there's no cure for DiGeorge syndrome. Treatment focuses on managing the medical problems that the chromosome defects cause.

The long-term outlook for children with DiGeorge syndrome varies widely, depending on the severity of their condition and the organs affected. For example, some children with mild forms of DiGeorge syndrome may have a normal life expectancy, while others with more severe forms have a reduced life expectancy. Some children have no restrictions on their activities, while others — particularly those with complex heart defects — may need to avoid some activities.

Parathyroid glands
When a baby's parathyroid glands are smaller than normal, they often can't produce enough parathyroid hormone (PTH) to properly regulate the amount of calcium and phosphorus in the body (hypoparathyroidism). To regulate calcium and phosphorus, treatment of hypoparathyroidism often includes calcium supplements, a low phosphorus diet and vitamin D.

If enough of the parathyroid tissue is intact, it's possible your child's parathyroid glands will be able to begin correctly regulating their production of PTH within the first year of life, which usually eliminates hypoparathyroidism.

Thymus gland
If part or all of your child's thymus gland is missing, he or she may need to take antibiotics or another type of medication, called immune globulin, to help prevent infection. Also to prevent infection, a child with decreased thymic function may need to avoid live virus vaccinations. A thymic tissue transplant may be an option for restoring immune function in some severe cases.

Because the thymus gland is less important in fighting infection in adults than it is in children, as he or she ages, your child may outgrow problems related to decreased thymus function.

Heart
Although some heart defects, such as a small ventricular septal defect, don't require treatment, surgery may be necessary to correct your baby's heart defect and avoid long-term complications.

Prevention

In rare cases, DiGeorge syndrome may be passed from affected parent to child through defective genes. If you're concerned about a family history of DiGeorge syndrome, or if you already have a child with DiGeorge syndrome, you may wish to consult your doctor or a genetic counselor for help in planning future pregnancies.

Coping and support

Finding out your child has DiGeorge syndrome can be difficult. You may not know what to expect, and you may worry about your own ability to care for a baby with medical concerns. The best cure for fear and worry is to arm yourself with information and help.

Find a team of doctors and therapists you trust to help you with the important decisions you'll need to make about your child's care and treatment. These professionals can also help identify and evaluate appropriate resources in your area.

Each family and each child with DiGeorge syndrome is different. But connecting with other families facing the same problems can help you feel less alone. Ask your child's doctor for information about support groups and other organizations in your area that can help.