22q11.2 Deletion Syndrome in Children

The 22q11.2 deletion syndrome (22q11.2DS) is a genetic disorder. In children with this syndrome, a tiny piece of chromosome 22 is missing. This can cause many health problems. These problems may range from heart defects and developmental delays to seizures. The child may also have changes in how the eyes, nose, or ears look. Or the child may have an opening in the roof of the mouth (cleft palate), or decreased movement of the palate. Most children with the syndrome have only some of the health problems. In general, many of the health problems can be treated, especially if they are found early.

The name of the syndrome refers to the missing piece of chromosome 22. It is located at a specific place on that chromosome called q11.2.

The symptoms of 22q11.2DS can vary greatly from one child to another. For that reason, several disorders caused by 22q11.2DS have had other names in the past. These names include:

• DiGeorge syndrome
• Velocardiofacial syndrome
• Shprintzen syndrome
• Conotruncal anomaly face syndrome
• Sedlackova syndrome
• CATCH 22 syndrome

Some children with the syndrome had been diagnosed with a form of Opitz G/BBB syndrome or Cayler cardiofacial syndrome in the past. Healthcare providers now know that these disorders all share the same genetic cause as 22q11.2DS.

About 1 in 4,000 people have 22q11.2DS. But some experts believe this number is higher. Some parents who have a child with this chromosome problem may not know it because the symptoms are less severe.

Most children with 22q11.2DS are missing approximately 46 genes. Researchers don’t yet know the exact function of many of these genes. Missing the TBX1 gene on chromosome 22 may likely cause the syndrome's most common physical symptoms. These include heart problems and cleft palate.

The loss of another gene (called COMT), along with other common genetic risk factors for mental health disease, may also explain the higher risk for behavior problems and mental illness.

About 9 in 10 cases of 22q11.2DS happen by chance (randomly). They are present at the time when the egg is fertilized. Or they occur early in a baby’s growth in the mother’s uterus. This means that most children with the disorder have no family history of it.

But a person with the condition can pass it on to their children. About 1 in 10 cases are inherited from the mother or the father. When the condition is inherited, other family members could also be affected. A person who has this chromosome deletion has a 1 in 2 chance of passing the problem to a child. So both parents can have their blood studied to look for the deletion.

A child is more at risk for this disorder if they have a parent who has the condition or is carrying the faulty chromosome. But most cases occur randomly.

Symptoms of 22q11.2DS may vary widely, even among family members. Many symptoms have been seen with this disorder. Most children have only some of the symptoms.

The most common symptoms include:

• Heart defects. These are usually present from birth (congenital).
• Mouth problems. These include cleft palate and a palate that does not move normally (velopharyngeal insufficiency). These can cause speech problems.
• Ear problems. This includes middle ear infections or hearing loss.
• Low levels of calcium in the blood. This is caused by problems with the parathyroid glands and can set off seizures.
• Immune system problems. These can increase the risk for infections.
• Spine problems. These include curvature of the spine (scoliosis) and problems with the bones of the neck or upper back.
• Learning problems. These include delays in development and speech.
• Communication and social problems. This includes autism.
• Increased risk for mental illness. This includes anxiety, depression, or schizophrenia in adulthood.
• Feeding difficulties. These may occur because of a cleft palate, gastroesophageal reflux, or other issues. 
• Kidney problems. These may include an abnormally shaped kidney or a missing kidney.

Facial features of children may include: 

• Small ears with squared upper ear
• Hooded eyelids
• Cleft lip, cleft palate, or both
• Uneven (asymmetric) face when crying
• Small mouth, chin, and side areas of the tip of the nose

The symptoms of 22q11.2DS can be like other health conditions. Make sure your child sees their healthcare provider for a diagnosis.

Your child’s healthcare provider will look at your child’s prenatal history and complete health and family history. They will do a physical exam. Your child may need certain tests. These may include:

• Blood tests. These are to look for immune system problems.
• X-ray. This test makes pictures of internal tissues, bones, and organs. 
• Echocardiography. This test looks at the structure of the heart and how well it is working.
• Fluorescent in situ hybridization (FISH) studies. This blood test looks at a specific spot in the 22q11.2 region to see if it is deleted. If the FISH test doesn’t find any deletion in the 22q11.2 region of the chromosome but your child has signs of the syndrome, they will usually need a full chromosome study. This will look for other chromosome problems.
• Chromosomal microarray. This is similar to a FISH test. But it looks at many regions across all the chromosomes, including chromosome 22. This is to find a missing piece in the 22q11.2 location. This test is done more commonly than the FISH test to look for the deletion.
• Exome or genome sequencing. This testing looks at the spelling of the DNA letters in either all of the genes (exome) or the entire genome. Missing pieces of chromosome 22 can also be detected.

There is no cure for 22q11.2DS. But many of its related health problems can be treated. You can help your child by seeking early care.

Treatment will depend on your child’s symptoms, age, and general health. It will also depend on how bad the condition is.

Treatment may include working with specialists. This may include any of the following:

• Cardiologist. They will look at any heart defects. The cardiologist may correct them with a procedure or surgery.
• Plastic surgeon, otolaryngologist or oral and maxillofacial surgeon, and speech pathologist. They will look at any cleft lip or cleft palate defects.
• Speech and digestive specialists. They will look at any feeding problems. Some children with the syndrome have severe feeding problems. They may need tube feedings in order to get enough nutrition.
• Immune system specialist. Your child should be checked by this type of specialist. If your child has a T cell problem, they are at risk for infections that keep coming back. Your child should not have any live viral vaccines. Your child should have any blood products for a transfusion irradiated. This is true unless your child’s immune system healthcare provider says that it is not needed.
• Neurology and developmental pediatric specialist. Learning, developmental, and behavioral difficulties are common. This type of healthcare provider can screen for, as well as keep track of and address, these problems if they occur.
• Endocrinologist. This specialist treats problems of the endocrine system. Your child may have parathyroid glands that haven't fully developed. This can result in hypocalcemia, which causes low calcium levels. It's a potentially life-threatening side effect of the syndrome.

Other common problems that may need treatment include:

• Low calcium. This is common in children with the syndrome, especially right after birth. But it can also happen during times of stress, such as during puberty or after surgery. Your child may need to take calcium and vitamin D supplements.
• Development problems. Young children with 22q11.2DS may be slow to meet developmental milestones. These include sitting, walking, and talking. The International 22q11.2 Deletion Syndrome Foundation recommends that parents consider physical therapy (PT), occupational therapy (OT), and speech therapy for their child. PT strengthens large muscles and helps children meet developmental milestones. OT focuses on small muscles used for tying shoes, buttoning clothes, and other tasks. It can also help with feeding problems. Speech therapy can help your child with language delays.

A small number of children with severe heart defects and immune system problems caused by 22q11.2DS will not survive the first year of life. But most children with the syndrome who get treatment will survive and grow into adulthood. These children will likely need extra help throughout school. They may also need long-term care for their health needs.

Some children with the syndrome may have behavioral conditions. These include autism, attention deficit disorder, obsessive compulsive disorder, schizophrenia, or anxiety.

Most cases of 22q11.2DS occur randomly. So the disease can’t always be prevented. In about 1 in 10 cases of the syndrome, the deletion is inherited from one of the parents. Think about having genetic testing and counseling to find out if this disorder is inherited. Some of the screening tests during a pregnancy may be able to find this condition before a baby is born. If you have the 22q11.2 deletion, you have a 1 in 2 chance of passing it on to a child. This is true for every pregnancy you have.

Most health problems caused by 22q11.2DS can be treated, especially if they are found early. Here are things you can do to help your child:

• Keep all appointments with your child’s healthcare provider.
• Call the healthcare provider if you are concerned about your child’s symptoms.
• Tell others of your child’s condition. Work with your child’s healthcare provider and school to come up with a treatment plan.
• Think about getting genetic testing and counseling to understand whether 22q11.2DS is an inherited condition in your family.

Call the healthcare provider if your child has:

• Symptoms that don’t get better, or get worse
• New symptoms

• 22q11.2DS deletion syndrome is a genetic disorder where a tiny piece of chromosome 22 is missing.
• Most cases happen randomly as a baby grows in the mother’s uterus. It can also be inherited. About 1 in 10 cases are inherited.
• Symptoms vary widely and can range from heart defects and developmental delays to seizures. A child’s eyes, nose, or ears may look different. Or the child may have an opening in the roof of the mouth (cleft palate).
• The syndrome has no cure. But many related health problems can be treated. You can help your child by seeking early care.
• Most children who get treatment early will survive and grow into adulthood. They will likely need extra help throughout school. They may also need long-term care for their health needs.
• A person with this condition has a 1 in 2 chance of passing the problem to a child. So genetic testing and counseling are important.

Tips to help you get the most from a visit to your child’s healthcare provider:

• Know the reason for the visit and what you want to happen.
• Before your visit, write down questions you want answered.
• At the visit, write down the name of a new diagnosis and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you for your child.
• Know why a new medicine or treatment is prescribed and how it will help your child. Also know what the side effects are.
• Ask if your child’s condition can be treated in other ways.
• Know why a test or procedure is recommended and what the results could mean.
• Know what to expect if your child does not take the medicine or have the test or procedure.
• If your child has a follow-up appointment, write down the date, time, and purpose for that visit.
• Know how you can contact your child’s healthcare provider after office hours. This is important if your child becomes ill and you have questions or need advice.