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22q11.2 Deletion Syndrome

What is 22q11.2 deletion syndrome?

22q11.2 deletion syndrome is a genetic disorder with varying conditions present in each individual with the syndrome. In this syndrome, a tiny piece of chromosome 22 is missing. This can cause many medical problems. These problems may range from heart defects and developmental delays to seizures and effects on facial appearance, such as cleft palate (an opening in the roof of the mouth due to a birth defect).

In 22q11.2 deletion syndrome, a tiny piece of chromosome 22 is missing from the long arm of chromosome 22 at a location called q11.2. 

Most people affected by the syndrome do not experience all the health problems that are associated with it. In general, health problems that are present due to 22q11.2 deletion syndrome can be managed with treatment, especially if they are detected early. 

In the mid-1960s, an endocrinologist named Dr. Angelo DiGeorge recognized that a particular group of clinical features frequently occurred together, including the following: 

  • Hypoparathyroidism (underactive parathyroid gland), which results in hypocalcemia (low blood calcium levels) 

  • Hypoplastic (underdeveloped) thymus or absent thymus, which results in problems with the immune system 

  • Conotruncal heart defects (such as tetralogy of Fallot, interrupted aortic arch, ventricular septal defects, vascular rings) 

  • Cleft lip and/or palate

The signs and symptoms of 22q11.2 deletion syndrome can vary from one affected person to another. For that reason, several disorders and collections of symptoms caused by this syndrome have had other names in the past. These names, some of which are still used occasionally, include: 

  • DiGeorge syndrome

  • Velocardiofacial syndrome (VCFS)

  • Shprintzen syndrome

  • Conotruncal anomaly face syndrome (CTAF)

  • Sedlackova syndrome

In addition, some children with the syndrome were previously diagnosed with Opitz G/BBB syndrome or Cayler cardiofacial syndrome. Doctors now understand that these disorders all share the same genetic cause as 22q11.2 deletion syndrome. 

Who is affected by 22q11.2 deletion syndrome?

About one in 4,000 people have 22q11.2 deletion syndrome. Some medical experts believe this number should be higher because some people with the chromosome defect have less severe symptoms that may not be diagnosed as 22q11.2 deletion syndrome. Thus, they are unaware they have the syndrome. 

What causes 22q11.2 deletion syndrome?

Most people with 22q11.2 deletion syndrome are missing about 30 to 40 genes. The exact function of many of these genes remains a mystery. But one gene, TBX1, probably accounts for the syndrome's most common physical symptoms, including heart problems and cleft palate. Another nearby gene, called COMT, may also help explain the increased risk for behavior problems and mental illness in people with the syndrome. 

About 90 percent of 22q11.2 deletion syndrome cases occur randomly at fertilization or early in fetal development. So most people affected with the disorder have no previous family history of it. However, they may pass the condition on to their children. The remaining 10 percent of cases are inherited from either the mother or the father. When the condition is inherited, other family members could also be affected. Because a person who has this chromosome deletion has a 50 percent chance of passing the deletion to a child, both parents are generally offered the opportunity to have their blood studied to look for the deletion. 

What are the signs and symptoms of 22q11.2 deletion syndrome?

The signs and symptoms of 22q11.2 deletion syndrome may vary widely, even among family members. At least 30 different signs or symptoms have been associated with this disorder, but most affected people only have some symptoms.  

The most common symptoms include: 

  • Heart defects, which are usually present from birth 

  • Palate abnormalities, such as cleft palate and speech difficulties 

  • Middle ear infections or hearing loss 

  • Feeding difficulties 

  • Low levels of calcium in the blood, due to problems with the parathyroid glands, which can trigger seizures 

  • Immune system problems that can increase risk for infections 

  • Kidney abnormalities 

  • Spine problems, such as scoliosis (curvature in the spine) and abnormalities in the bones of  the neck or upper back 

  • Learning difficulties, especially with nonverbal material, and developmental delays 

  • Communication and social interaction problems, including autism 

  • An increased risk for  mental illness, such as anxiety, depression, or schizophrenia in adulthood

Facial features of children with 22q11.2 deletion syndrome may include the following: 

  • Small ears with squared upper ear

  • Hooded eyelids

  • Cleft lip and/or palate

  • Asymmetric facial appearance when crying

  • Small mouth, chin, and side areas of the nose tip 

The symptoms of 22q11.2 deletion syndrome may resemble other problems or medical conditions. Always consult your child's doctor for a diagnosis. 

How is 22q11.2 deletion syndrome diagnosed?

In addition to a prenatal history, complete medical and family history, and a physical examination, diagnostic procedures for 22q11.2 deletion may include: 

  • Blood tests and tests to examine for immune system problems

  • X-ray. A diagnostic test which uses invisible electromagnetic energy beams to produce images of internal tissues, bones, and organs onto film. 

  • Echocardiography. A procedure that evaluates the structure and function of the heart by using sound waves recorded on an electronic sensor that produce a moving picture of the heart and heart valves. 

  • Fluorescent in situ hybridization (FISH) studies. When features of conotruncal heart defects, clefting, other facial features, hypocalcemia, and absent thymus are identified, a blood test is usually ordered to look for a deletion in the chromosome 22q11.2 region. FISH is specifically designed to look for small groups of genes that are deleted. If the FISH test finds no deletion in the 22q11.2 region and the features of VCFS are still strongly suggestive, then a full chromosome study is usually performed to look for other chromosome defects that have been associated with this syndrome. 

If a 22q11.2 deletion is detected in a child, then both parents are offered the FISH test to see if this deletion is inherited. In approximately 10 percent of families, the deletion has been inherited from one of the parents. Any individual who has this 22q11.2 deletion has a 50 percent chance, with each pregnancy, of passing it on to a child.           

How is 22q11.2 deletion syndrome treated?

There is no cure for 22q11.2 deletion syndrome, but many of its related health problems can be treated. Parents can help their child by seeking early, competent care.  

Specific treatment for 22q11.2 deletion syndrome will be determined by your child's doctor based on the following: 

  • Your child's age, overall health, and medical history

  • The extent of the disease

  • The type of disease

  • Your child's tolerance for specific medications, procedures, or therapies

  • Expectations for the course of the disease

  • Your opinion or preference 

Treatment will also depend on the particular features in any given child and may include the following: 

  • Heart defects will be evaluated by a cardiologist and may be corrected with interventional procedure or surgery. 

  • A plastic surgeon and a speech pathologist will evaluate cleft lip and/or palate defects. 

  • Speech and gastrointestinal specialists will evaluate feeding difficulties. Some children with the syndrome have severe feeding difficulties and need tube feedings in order to get adequate nutrition. Feeding difficulties are not usually related to heart or palate problems, but rather to intestinal problems caused by the syndrome. 

  • Immunology evaluations should be performed in all children with this deletion. To monitor T-cell disorder and recurrent infections, live viral vaccines should be avoided and all blood products for transfusions (if needed) should be irradiated unless cleared by an immunology doctor. 

Other common problems that may require treatment include: 

  • Low calcium. This is common in children with the syndrome, especially right after birth. But it can also recur during stressful periods, such as during puberty or following surgery. A child may need to take calcium supplements as well as vitamin D to help absorb the calcium. A referral to an endocrinologist (doctor who specializes in treating conditions affecting the endocrine system0 may be recommended.

  • Developmental difficulties. Young children with 22q11.2 deletion syndrome may be slow to achieve developmental milestones, such as 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 affected children. PT strengthens large muscles and helps children meet developmental milestones. OT focuses on small muscles used for skills, such as tying shoes and buttoning clothes. It can also help with feeding problems. Speech therapy can help address language delays that may become apparent after a child turns one year old. 

A child's doctor or parents may request an evaluation to determine what services are available to assist in the management of a child with 22q11.2 deletion syndrome. 

Long-term outlook for children with 22q11.2 deletion syndrome

A small percentage of children with severe heart defects and immune system problems caused by 22q11.2 deletion syndrome will not survive the first year of life. However, with the proper treatment of heart defects, immune system disorders, and other health problems, the vast majority of children with a 22q11.2 deletion will survive and grow into adulthood. These children will generally need extra help throughout school and will need long-term care for their individual health needs. 

Although it is not common, some children with the syndrome may have behavioral conditions such as autism, attention deficit disorder (ADD/ADHD), obsessive compulsive disorder (OCD), or anxiety. According to the Velo-Cardio-Facial Syndrome Educational Foundation, most individuals with the syndrome have some behavioral problems. The occurrence of psychiatric disorders is higher for adults with 22q11.2 deletion syndrome, but medical researchers are still investigating the exact nature and risk of these disorders.