DiGeorge syndrome (22q11.2 deletion syndrome)

DiGeorge syndrome, more accurately known by a broader term — 22q11.2 deletion syndrome — is a disorder caused when a small part of chromosome 22 is missing. This deletion results in the poor development of several body systems.

The term 22q11.2 deletion syndrome covers terms once thought to be separate conditions, including DiGeorge syndrome, velocardiofacial syndrome and other disorders that have the same genetic cause, though features may vary slightly.

Medical problems commonly associated with 22q11.2 deletion syndrome include heart defects, poor immune system function, a cleft palate, complications related to low levels of calcium in the blood, and delayed development with behavioral and emotional problems.

The number and severity of symptoms associated with 22q11.2 deletion syndrome vary. However, almost everyone with this syndrome needs treatment from specialists in a variety of fields.

Symptoms

Signs and symptoms of DiGeorge syndrome (22q11.2 deletion syndrome) can vary in type and severity, depending 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:

• Heart murmur and bluish skin due to poor circulation of oxygen-rich blood (cyanosis) as a result of a heart defect
• Frequent infections
• Certain facial features, such as an underdeveloped chin, low-set ears, wide-set eyes or a narrow groove in the upper lip
• A gap in the roof of the mouth (cleft palate) or other problems with the palate
• Delayed growth
• Difficulty feeding, failure to gain weight or gastrointestinal problems
• Breathing problems
• Poor muscle tone
• Delayed development, such as delays in rolling over, sitting up or other infant milestones
• Delayed speech development or nasal-sounding speech
• Learning delays or disabilities
• Behavior problems

When to see a doctor

Other conditions may cause signs and symptoms similar to 22q11.2 deletion syndrome. So it's important to get an accurate and prompt diagnosis if your child shows any signs or symptoms listed above.

Doctors may suspect 22q11.2 deletion syndrome:

• At birth. If certain conditions — a severe heart defect, cleft palate or a combination of other factors typical of 22q11.2 deletion syndrome — are readily apparent at birth, diagnostic tests will likely begin before your child leaves the hospital.
• At well-baby visits. 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.

Causes

Each person has two copies of chromosome 22, one inherited from each parent. If a person has DiGeorge syndrome (22q11.2 deletion 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 is known as 22q11.2.

The deletion of genes from chromosome 22 usually occurs as a random event in the father's sperm or in the mother's egg, or it may occur early during fetal development. Rarely, the deletion is an inherited condition passed to a child from a parent who also has deletions in chromosome 22 but may or may not have symptoms.

Complications

The portions of chromosome 22 deleted in DiGeorge syndrome (22q11.2 deletion 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 22q11.2 deletion syndrome include:

• Heart defects. 22q11.2 deletion syndrome often causes heart defects that could result in an insufficient supply of oxygen-rich blood. For example, 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); or a combination of four abnormal heart structures (tetralogy of Fallot).
• Hypoparathyroidism. The four parathyroid glands in the neck regulate the levels of calcium and phosphorus in the body. 22q11.2 deletion syndrome can cause smaller than normal parathyroid glands that secrete too little parathyroid hormone (PTH), leading to hypoparathyroidism. This condition results in low levels of calcium and high levels of phosphorus in the blood.
• Thymus gland dysfunction. The thymus gland, located beneath the breastbone, is where T cells — a type of white blood cell — mature. Mature T cells are needed to help fight infections. In children with 22q11.2 deletion syndrome, the thymus gland may be small or missing, resulting in poor immune function and frequent, severe infections.
• Cleft palate. A common condition of 22q11.2 deletion syndrome is a cleft palate — an opening (cleft) in the roof of the mouth (palate) — with or without a cleft lip. Other, less visible abnormalities of the palate that may also be present can make it difficult to swallow or produce certain sounds in speech.
• Distinct facial features. A number of particular facial features may be present in some people with 22q11.2 deletion syndrome. These may include small, low-set ears, short width of eye openings (palpebral fissures), hooded eyes, a relatively long face, an enlarged nose tip (bulbous), or a short or flattened groove in the upper lip.
• Learning, behavioral and mental health problems. 22q11.2 deletion may cause problems with development and function of the brain, resulting in learning, social, developmental or behavioral problems. Delays in toddler speech development and learning difficulties are common. Some children develop attention-deficit/hyperactivity disorder (ADHD) or autism spectrum disorder. Later in life, the risk of depression, anxiety disorders and other mental health disorders increases.
• Autoimmune disorders. People who had poor immune function as children, due to a small or missing thymus, may also have an increased risk of autoimmune disorders, such as rheumatoid arthritis or Graves' disease.
• Other problems. A large number of medical conditions may be associated with 22q11.2 deletion syndrome, such as hearing impairment, poor vision, breathing problems, poor kidney function and relatively short stature for one's family.

Prevention

In some cases, DiGeorge syndrome (22q11.2 deletion syndrome) may be passed from an affected parent to a child. If you're concerned about a family history of 22q11.2 deletion syndrome, or if you already have a child with the syndrome, you may want to consult a doctor who specializes in genetic disorders (geneticist) or a genetic counselor for help in planning future pregnancies.

Diagnosis

A diagnosis of DiGeorge syndrome (22q11.2 deletion syndrome) is based primarily on a lab test that can detect the deletion in chromosome 22. Your doctor will likely order this test if your child has:

• A combination of medical problems or conditions suggesting 22q11.2 deletion syndrome
• A heart defect, because certain heart defects are commonly associated with 22q11.2 deletion syndrome

In some cases, a child may have a combination of conditions that suggest 22q11.2 deletion syndrome, but the lab 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.

Treatment

Although there is no cure for DiGeorge syndrome (22q11.2 deletion syndrome), treatments can usually correct critical problems, such as a heart defect or cleft palate. Other health issues and developmental, mental health or behavioral problems can be addressed or monitored as needed.

Treatments and therapy for 22q11.2 deletion syndrome may include interventions for:

• Hypoparathyroidism. Hypoparathyroidism can usually be managed with calcium supplements and vitamin D supplements.
• Heart defects. Most heart defects associated with 22q11.2 deletion syndrome require surgery soon after birth to repair the heart and improve the supply of oxygen-rich blood.
• Limited thymus gland function. If your child has some thymic function, infections may be frequent, but not necessarily severe. These infections — usually 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 improves with age.
• Severe thymus dysfunction. If the impairment of the thymus is severe or there's no thymus, your child is at risk of 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 and lip can usually be surgically repaired.
• Overall development. Your child will likely benefit from a range of therapies, including speech therapy, occupational therapy and developmental therapy. In the United States, early intervention programs providing these types of therapy are usually available through a state or county health department.
• Mental health care. Treatment may be recommended if your child is later diagnosed with attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, depression, or other mental health or behavioral disorders.
• Management of other conditions. These may include addressing feeding and growth issues, hearing or vision problems, and other medical conditions.

Health care team

Because 22q11.2 deletion syndrome can result in so many problems, several 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 on your care team may include these professionals and others, as needed:

• Children's health specialist (pediatrician)
• Expert in inherited disorders (geneticist)
• Heart specialist (cardiologist)
• Immune system specialist (immunologist)
• Ear, nose and throat (ENT) specialist
• Infectious disease specialist
• Hormone disorder specialist (endocrinologist)
• Surgeon who specializes in correcting such conditions as a cleft palate (oral and maxillofacial surgeon)
• Surgeon who specializes in correcting heart defects (cardiovascular surgeon)
• Occupational therapist to help develop practical, everyday skills
• Speech therapist to help improve verbal skills and articulation
• Developmental therapist to help develop age-appropriate behaviors, social skills and interpersonal skills
• Mental health professional, such as a pediatric psychiatrist or psychologist

Coping and support

Having a child with DiGeorge syndrome (22q11.2 deletion syndrome) is challenging. You must deal with numerous treatment issues, manage your own expectations and meet the needs of your child. Ask your health care team about organizations that provide educational materials, support groups and other resources for parents of children with 22q11.2 deletion syndrome.

Preparing for an appointment

Your doctor may suspect DiGeorge syndrome (22q11.2 deletion syndrome) at birth, in which case diagnostic tests and treatment will likely begin before your child leaves the hospital.

Your child's health care provider will look for developmental problems at regular checkups and give you the opportunity to discuss any concerns with your doctor. It's important to take your child to all regularly scheduled well-baby visits and annual appointments.

Here's some information to help you prepare for your appointment.

What you can do

If your family doctor or pediatrician believes that your child shows signs of 22q11.2 deletion syndrome, basic question to ask include:

• What diagnostic tests will be needed?
• When will we know and how will we get the results of the tests?
• What specialists will you refer us to?
• What medical conditions related to this syndrome need to be addressed right now? What's 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 this syndrome?
• What services are available for early childhood development?

What to expect from your doctor

Be prepared to answer questions the doctor may ask, such as:

• 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?

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