DiGeorge syndrome

Definition

DiGeorge syndrome (22q11.2 deletion syndrome), a disorder caused by a defect in chromosome 22, results in the poor development of several body systems.

Medical problems commonly associated with DiGeorge syndrome include heart defects, poor immune system function, a cleft palate, complications related to low levels of calcium in the blood and behavioral disorders.

The number and severity of problems associated with DiGeorge syndrome vary greatly. Almost everyone with DiGeorge syndrome needs treatment from specialists in a variety of fields.

Before the discovery of the chromosome 22 defect, the disorder was known by several names — DiGeorge syndrome, velocardiofacial syndrome and others. Although the term "22q11.2 deletion syndrome" is frequently used today — and is generally a more accurate description — previous names for the disorder are still used.

Symptoms

Signs and symptoms of DiGeorge syndrome can vary significantly in type and severity. This variation depends on what body systems are affected and how severe the defects are. Some signs and symptoms may be apparent at birth, but others may not appear until later in infancy or early childhood.

Signs and symptoms may include some combination of the following:

• Bluish skin due to poor circulation of oxygen-rich blood (cyanosis)
• Weakness or tiring easily
• Failure to thrive
• Failure to gain weight
• Poor muscle tone
• Shortness of breath
• Twitching or spasms around the mouth, hands, arms or throat (tetany)
• Frequent infections
• Difficulty feeding
• Delayed development, such as delays in rolling over, sitting up or other infant milestones
• Delayed speech development
• Learning delays or difficulties
• A gap in the roof of the mouth (cleft palate) or other problems with the palate
• Certain facial features, such as low-set ears, wide-set eyes or a narrow groove in the upper lip

When to see a doctor
Other conditions may cause the signs and symptoms of DiGeorge syndrome. So it's important to get an accurate and prompt diagnosis if your child exhibits any signs or symptoms of the disorder.

If your child has any of the following signs and symptoms, seek immediate medical care:

• Bluish skin
• Twitching or spasms around the mouth, hands, arms or throat
• Seizures

Causes

DiGeorge syndrome is caused by the deletion of a portion of chromosome 22. Each person has two copies of chromosome 22, one inherited from each parent. This chromosome contains an estimated 500 to 800 genes.

If a person has DiGeorge syndrome, one copy of chromosome 22 is missing a segment that includes an estimated 30 to 40 genes. Many of these genes haven't been clearly identified and aren't well understood. The region of chromosome 22 that's deleted in DiGeorge syndrome is known as 22q11.2. A small number of people with DiGeorge syndrome have a shorter deletion in the same region of chromosome 22.

The deletion of genes from chromosome 22 usually occurs randomly in the father's sperm or in the mother's egg, or it may occur very early during fetal development. Therefore, the deletion is repeated in all or nearly all of the cells in the body as the fetus develops.

Complications

The portions of chromosome 22 deleted in DiGeorge syndrome play a role in the development of a number of body systems. As a result, the disorder can cause several errors during fetal development. Common problems that occur with DiGeorge syndrome include:

• Heart defects. DiGeorge syndrome often causes heart defects that result in an insufficient supply of oxygen-rich blood for the body. These defects may include a hole between the lower chambers of the heart (ventricular septal defect); only one large vessel, rather than two vessels, leading out of the heart (truncus arteriosus); and a combination of four abnormal heart structures (tetralogy of Fallot).
• Hypoparathyroidism. The four parathyroid glands are oval, grain-of-rice-sized glands located in your neck. These glands maintain proper levels of calcium and phosphorus in your body by turning off or on the secretion of parathyroid hormone (PTH). DiGeorge syndrome can result in smaller than normal parathyroid glands that secrete too little PTH (hypoparathyroidism). Hypoparathyroidism results in low levels of calcium and high levels of phosphorus in the blood.
• Thymus gland dysfunction. The thymus gland in children, located beneath the breastbone, is where T cells — a type of white blood cell — mature. Mature T cells are needed to help fight infections. As you grow older, the thymus decreases in size, and other parts of your body take over the role of the thymus in the immune system. In children with DiGeorge syndrome, the thymus gland may be small or missing, resulting in poor immune function and frequent, severe infections.
• Cleft palate. A common condition of DiGeorge syndrome is a cleft palate — an opening (cleft) in the roof of the mouth (palate). Other, less visible abnormalities of the palate that may also be present can make it difficult to swallow or produce certain sounds in speech.
• Facial features. A number of particular facial features may be present in some people with DiGeorge syndrome. These may include small, low-set ears, wide-set eyes, hooded eyes, a relatively long face or a short or flattened groove in the upper lip.
• Learning, behavioral and mental health problems. The 22q11.2 deletion may cause problems with the development and function of the brain, resulting in learning, social, developmental or behavioral problems. Delays in toddler speech development and learning difficulties are common. A number of children with DiGeorge syndrome develop disorders, such as attention-deficit/hyperactivity disorder (ADHD), autism or autism-related disorders. Later in life people with DiGeorge syndrome are at increased risk of mental health problems, including depression, anxiety disorders, schizophrenia and other psychiatric disorders.
• Autoimmune disorders. People who had poor immune function as children, due to a small or missing thymus, may have an increased risk of autoimmune disorders, such as rheumatoid arthritis and Graves' disease.
• Other problems. A large number of medical conditions may be associated with DiGeorge syndrome. These include hearing impairment, poor vision, poor kidney function and relatively short stature for one's family.

Lymphatic system

Lymphatic system

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 ...

Parathyroid glands

Parathyroid glands

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. ...

Truncus arteriosus

Truncus arteriosus

If your baby has truncus arteriosus, one very large vessel leads out of the heart, instead of two separate vessels, and there's a hole in the wall between the ventricles (ventricle septal defect). ...

Ventricular septal defect

Ventricular septal defect

A ventricular septal defect is an abnormal opening between the heart's lower pumping chambers. It's a common congenital heart defect that may heal on its own or require treatment to repair. ...

Tetralogy of Fallot

Tetralogy of Fallot

Tetralogy of Fallot is a combination of four congenital abnormalities. The four defects are a ventricular septal defect (VSD), pulmonary stenosis, a misplaced aorta and a thickened right ventricular ...

Cleft palate

Cleft palate

In a cleft palate, the roof of the mouth doesn't fuse together. As a result, the lip and the bridge to the nose are also left open. ...

Preparing for your appointment

How you learn about your child's condition — if your child has DiGeorge syndrome — depends greatly on the combination of medical problems that are present and their severity. If certain conditions — a severe heart defect, cleft palate or a combination of other factors typical of DiGeorge syndrome — are readily apparent at birth, diagnostic tests will likely begin before your child leaves the hospital.

Your family doctor or pediatrician may suspect the disorder because of a combination of illnesses or disorders that become apparent over time. Other issues may come to the attention of your doctor during regularly scheduled well-baby visits or annual checkups for your child.

Well-baby visits and annual checkups
It's important to take your child to all regularly scheduled well-baby visits and annual appointments. These visits can be important for identifying early signs of developmental delays and enable you to address concerns with your doctor.

Be prepared to answer questions that your child's doctor may ask:

• Does your baby have any problems feeding?
• Does your baby seem listless, weak or sick?
• Is your child reaching certain milestones in development, such as rolling over, pushing up, sitting up, crawling, walking or speaking?
• Do you observe any behaviors that concern you?

Talking to your doctor about DiGeorge syndrome
If your family doctor or pediatrician believes that your child exhibits signs or symptoms of DiGeorge syndrome and suggests diagnostic tests for the disorder, you may want to discuss the following questions:

• What diagnostic tests will be needed?
• When will we know the results of the tests?
• What specialists will you refer us to?
• What medical conditions related to DiGeorge syndrome need to be addressed right now? What is our highest priority?
• How will you help me monitor my child's health and development?
• Can you suggest educational materials and local support services regarding DiGeorge syndrome?
• What services are available for early childhood development?

Tests and diagnosis

A diagnosis of DiGeorge syndrome is based primarily on a laboratory test that can detect the deletion in chromosome 22. Your doctor will likely order such a test if a combination of medical problems or conditions suggests DiGeorge syndrome.

Because certain heart defects are commonly associated with DiGeorge syndrome, the presence of the heart defect itself may prompt your doctor to order a laboratory test for a chromosome 22 deletion.

In some cases, a child may have a combination of conditions that suggest DiGeorge syndrome, but the laboratory test doesn't indicate a deletion in chromosome 22. Although these cases present a diagnostic challenge, the coordination of care to address all of the medical, developmental or behavioral problems will likely be similar.

Health care team
Because DiGeorge syndrome can result in so many disorders, a number of specialists will likely be involved in diagnosing specific conditions, recommending treatments and providing care. This team will evolve as your child's needs change. Specialists in your care team may include the following professionals:

• Children's health specialist (pediatrician)
• Geneticist (expert in inherited disorders)
• Heart specialist (cardiologist)
• Immune system specialist (immunologist)
• Infectious disease specialist
• Hormone disorder specialist (endocrinologist)
• Oral and maxillofacial surgeon, who specializes in surgery to correct such conditions as a cleft palate
• Other surgical specialists
• Occupational therapist, who specializes in therapy to help your child develop practical, everyday skills
• Speech therapist
• Developmental therapist, who specializes in therapy to help your child develop age-appropriate behaviors, social skills and interpersonal skills
• Mental health professional, such as a pediatric psychologist or psychiatrist

Treatments and drugs

There is no cure for DiGeorge syndrome. Treatments can usually correct critical problems, such as a heart defect or low calcium levels. Care for developmental, mental health or behavioral problems are more challenging, and the outcomes are less predictable.

Treatments and therapy for a person with DiGeorge syndrome may include interventions for the following conditions:

• Hypoparathyroidism. Hypoparathyroidism can usually be managed with calcium supplements, vitamin D supplements and a low phosphorus diet. If enough of the parathyroid tissue is intact, it's possible your child's parathyroid glands will eventually regulate calcium and phosphorus levels without a specialized diet.
• Limited thymus gland function. If your child has some thymic function, infections may be frequent, but not necessarily severe. These infections — usually frequent colds and ear infections — are generally treated as they would be in any child. Most children with limited thymic function follow the normal schedule of vaccines. For most children with moderate thymus impairment, immune system function will improve as they grow older.
• Severe thymus dysfunction. If the impairment of the thymus is severe or there's no thymus, your child is vulnerable to a number of severe infections. Treatment requires a transplant of thymus tissue, specialized cells from bone marrow or specialized disease-fighting blood cells.
• Cleft palate. A cleft palate or other abnormalities of the palate can usually be surgically repaired.
• Heart defects. Most heart defects associated with DiGeorge syndrome require surgery to repair the heart and correct blood circulation.
• Overall development. Your child will likely benefit from a range of therapies, including speech therapy to improve verbal skills and articulation, occupational therapy to learn everyday skills and developmental therapy to learn age-appropriate behaviors, social skills and interpersonal skills. In the United States, early intervention programs providing these types of therapy are usually available through a state's health department.
• Mental health care. Psychotherapy and psychiatric medications may be recommended if your child is later diagnosed with attention-deficit/hyperactivity disorder (ADHD), depression, schizophrenia, or other mental health or behavioral disorders.

Coping and support

Having a child with DiGeorge syndrome is challenging. You must address numerous treatment issues, manage your own expectations and meet the needs of your child. Organizations such as the Velo-Cardio-Facial Syndrome Educational Foundation provide educational materials, support groups and other resources for parents of children with DiGeorge syndrome.

Prevention

In some cases, DiGeorge syndrome may be passed from an affected parent to a child. 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 a doctor who specializes in genetic disorders (geneticist) or a genetic counselor for help in planning future pregnancies.