DiGeorge syndrome (22q11.2 deletion syndrome)

Overview

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is a condition caused when a small part of chromosome 22 is missing. This deletion causes several body systems to develop poorly.

The term 22q11.2 deletion syndrome covers terms once thought to be different conditions. These terms include DiGeorge syndrome, velocardiofacial (vel-oh-cahr-dee-oh-fay-shell) syndrome and other conditions caused by the same missing part of chromosome 22. But features may vary slightly.

Medical problems commonly related to 22q11.2 deletion syndrome include heart problems, lowered immunity, a cleft palate, complications from low levels of calcium, various eye issues and autoimmune disorders. Complications also include hearing loss, skeletal differences, kidney and genital differences, and delayed development with behavioral and emotional problems.

The number and severity of symptoms related to 22q11.2 deletion syndrome vary. But specialists in various fields need to treat almost everyone with this syndrome.

Symptoms

Symptoms of DiGeorge syndrome can vary based on what body systems are affected and the severity of the problems. Some symptoms may be clear at birth, but others may not appear until later in infancy or as a young child, or as an adult.

Symptoms of DiGeorge syndrome may include:

• Heart issues, such as problems with the structure of the heart and vessels, or a heart murmur and bluish skin because of poor circulation of blood, also known as cyanosis.
• Frequent infections.
• Distinctive facial features, such as an underdeveloped chin, ears that look different, wide-set eyes, hooded eyes and an enlarged nose tip. Asymmetric crying facies also may be present. This is when muscles on one side of the mouth don't develop fully, causing that side of the mouth to droop when crying, though the face looks balanced at rest.
• A gap in the roof of the mouth, also known as a cleft palate, or other problems with the palate.
• A hard time feeding, failure to gain weight or stomach problems.
• Hearing loss.
• Poor muscle tone.
• Kidney problems.
• Poor vision and other eye problems.
• Low levels of calcium in the blood.
• Scoliosis.

Other symptoms may include:

• Delayed growth.
• 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.
• Behavioral problems.

When to see a doctor

Other conditions may cause symptoms like 22q11.2 deletion syndrome. It's important to get the right diagnosis quickly if your child shows any symptoms listed above.

Healthcare professionals may suspect 22q11.2 deletion syndrome:

• At birth. If a severe heart problem, cleft palate or other signs typical of 22q11.2 deletion syndrome are clear at birth, tests likely will be done before your child leaves the hospital.
• At well-baby visits. Illnesses or conditions that are typical of 22q11.2 deletion syndrome may become clear over time. Your child's healthcare professional may see issues during regularly scheduled well-baby visits or annual checkups.

Causes

Each person has two copies of chromosome 22 — one inherited from each parent. 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 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 when the baby is developing. Rarely, the deletion is passed to a child from a parent who also has a deletion in chromosome 22 but may have fewer or mild symptoms.

Complications

The portions of chromosome 22 missing in DiGeorge syndrome affect the development of several body systems. As a result, the condition can cause several errors during fetal development.

• Heart issues. 22q11.2 deletion syndrome often causes heart problems that could lead to too little oxygen-rich blood. For example, problems may include a hole between the lower chambers of the heart, also known as a ventricular septal defect. Or there may be only one large vessel rather than two vessels leading out of the heart, also known as truncus arteriosus. Or there may be four problems with heart structure, also known as 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 parathyroid glands to be smaller than usual and produce too little parathyroid hormone. This leads to hypoparathyroidism. This condition results in low levels of calcium and high levels of phosphorus in the blood.
• Thymus gland dysfunction. The thymus gland, which is beneath the breastbone, is where T cells — a type of white blood cell — mature. Mature T cells help fight infections. In children with 22q11.2 deletion syndrome, the thymus gland may be small or missing. This leads to poor immune function and frequent, severe infections.
• Cleft palate. A common condition of 22q11.2 deletion syndrome is a cleft palate, which is an opening in the roof of the mouth, with or without a cleft lip. Other, less visible problems with the structure of the palate can make it hard to swallow or make 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 syndrome may cause problems with development and function of the brain, resulting in learning, social, developmental or behavioral problems. Delays in toddler speech development and finding it hard to learn are common. Some children develop attention-deficit/hyperactivity condition (ADHD) or autism spectrum disorder. Later in life, the risk of depression, anxiety and other mental health conditions is higher.
• Autoimmune conditions. People with 22q11.2 deletion syndrome also may have a greater risk of getting autoimmune conditions, such as rheumatoid arthritis or Graves' disease.
• Other problems. Many medical conditions may be related to 22q11.2 deletion syndrome, such as hearing problems, eye problems and poor kidney function.

Prevention

In some cases, an affected parent may pass DiGeorge syndrome to a child. If you're worried about a family history of 22q11.2 deletion syndrome or if you already have a child with the syndrome, you may want to see a doctor who specializes in genetic conditions. This doctor is called a geneticist. Or you may want to see a genetic counselor to help plan 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 child's healthcare professional likely will order this test if your child has:

• A mix of medical problems or conditions suggesting 22q11.2 deletion syndrome.
• A heart problem because certain heart problems are commonly related to 22q11.2 deletion syndrome.

In some cases, a child may have a mix of conditions that suggest 22q11.2 deletion syndrome, but the lab test doesn't suggest a missing portion of chromosome 22.

Treatment

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

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

• Hypoparathyroidism. Taking calcium and vitamin D supplements as directed by your healthcare professional often can manage hypoparathyroidism. In some cases, other supplements also may be recommended.
• Heart problems. Most heart problems related to 22q11.2 deletion syndrome require surgery soon after birth to repair the heart and make the supply of oxygen-rich blood better.
• 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 — generally are treated as they would be in any child. Most children with limited thymic function follow the usual vaccination schedules. Immune system function improves with age for most children whose thymus has been moderately harmed.
• Severe thymus dysfunction. If the harm to the thymus is severe or there's no thymus, your child is at risk of several severe infections. Treatment may require a transplant of thymus tissue and specialized cells from bone marrow or specialized disease-fighting blood cells.
• Cleft palate. A cleft palate or other unusual features of the palate and lip usually can be repaired by surgery.
• Overall development. Your child likely will benefit from a range of therapies, including speech therapy, occupational therapy and developmental therapy. In the U.S., early intervention programs providing these types of therapy usually are 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 another mental health or behavioral condition.
• Management of other conditions. These conditions may include feeding and growth issues, hearing or vision problems, and other medical conditions.

Healthcare team

Because 22q11.2 deletion syndrome can lead to so many problems, several specialists likely will help diagnose specific conditions, recommend treatments and provide care. This team will change as your child's needs change.

Specialists on your child's care team may include these professionals and others, as needed:

• Children's health specialist, also known as a pediatrician.
• Expert in inherited conditions, also known as a geneticist.
• Heart specialist, also known as a cardiologist.
• Immune system specialist, also known as an immunologist.
• Ear, nose and throat specialist, also called an ENT.
• Infectious diseases specialist.
• Hormone condition specialist, also known as an endocrinologist.
• Surgeon who specializes in fixing conditions such as a cleft palate, also known as an oral and maxillofacial surgeon.
• Surgeon who specializes in correcting heart problems, also known as a cardiovascular surgeon.
• Occupational therapist to build practical, everyday skills.
• Speech therapist to improve the ability to speak.
• Developmental therapist to develop age-appropriate behaviors and social 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 could be dealing with multiple health issues and treatments. To help meet your child's and your own needs, ask the healthcare 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 child's doctor or other healthcare professional may suspect DiGeorge syndrome at birth. If so, tests and treatment likely will begin before your child leaves the hospital.

Your child's healthcare professional will look for developmental problems at regular checkups and talk about any concerns. 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 child's appointment.

What you can do

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

• What tests will be needed?
• When will we get the test results?
• What specialists will you refer my child to?
• What medical conditions related to this syndrome need to be dealt with now? What medical condition is most important?
• How will you help me watch for problems with my child's health and development?
• Can you suggest educational materials and local support services about this syndrome?
• What services are available for early childhood development?

What to expect from your doctor

Be prepared to answer questions the healthcare professional 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 see any behaviors that concern you?

Being ready for these questions will help you make the most of your time with your child's healthcare professional.