22q11.2 Deletion Disorders (DiGeorge Syndrome and Velocardiofacial Syndrome)

What is a 22q11.2 deletion?

Each chromosome is made of protein and deoxyribonucleic acid (DNA). Passed from parents to offspring, DNA contains the specific instructions that make each type of living creature unique. DNA is organized as 23 pairs of chromosomes. One pair, the sex chromosomes, consists of either two X chromosomes (XX), resulting in a girl, or one X and one Y chromosome (XY), resulting in a boy. The other 22 pairs of chromosomes are numbered 1 through 22. 22q11.2 identifies a specific chromosomal location.

A molecular test called Fluorescence In Situ Hybridization (abbreviated as FISH) tests for deletions of 22q11.2 that are too small to be seen under the microscope. Using the FISH test for 22q11.2, it was discovered that about 95% of patients with DiGeorge syndrome and VCFS have a deletion. This special FISH test for 22q11.2 deletions is available in many clinical laboratories that look at chromosomes (referred to as cytogenetics laboratories).  This test is performed only when physicians instruct the laboratory that they suspect a 22q11.2 deletion in a person or fetus. That is, this FISH test is not done routinely for every amniocentesis (procedure where fluid and cells surrounding a developing fetus are sampled) or from every blood sample from patients.

If the FISH test for 22q11.2 deletion is negative, can my child still have a 22q11.2 deletion?

Yes! As noted in the previous section, the majority of patients with DiGeorge syndrome or Velocardiofacial Syndrome (VCFS) will have a positive FISH test. However, if the doctors caring for your child make the diagnosis of DiGeorge syndrome or VCFS on the basis of certain typical features (facial appearance, heart disease, etc.), then that remains true even if the FISH tests are normal.

Does the diagnosis of 22q11.2 deletion change the care of my child’s heart problem?

Babies born with 22q11.2 deletion frequently have heart defects. Those defects range in severity from mild to life-threatening. Those with the more serious forms of heart involvement will require surgery in the newborn and infancy period.  In general, decisions about the timing and the type of surgery that these young patients require is not affected by the diagnosis of a 22q11.2 deletion syndrome.

Varying degrees of immune system dysfunction may be present. If the immune system is abnormal, there is a somewhat higher risk of certain types of infection or other complications after the heart surgery.

If my child has 22q11.2 deletion syndrome, what is the risk for my other children or others in our family?

Most children with a 22q11.2 deletion are the first person in their family to have that problem. There is a small risk of new 22q11.2 deletion for any pregnancy.

When someone with a 22q11.2 deletion has children of their own, there is a 50-50 chance of passing along a copy of chromosome 22 with that deletion with each pregnancy. This also means, of course, that there is an equal chance that their next child will not inherit the deletion. Like flipping coins for heads or tails, the results of previous pregnancies do not necessarily affect the next one. So, a person with a 22q11.2 deletion and a first child who did not inherit the deletion has the same 50-50 risk with their second child.

In some cases, a parent of a child with a 22q11.2 deletion is also found to have that problem. Once an infant or child is identified as having the deletion, the geneticists will often take a history concerning the parents and examine them in order to decide whether or not one of the parents has it too. Since the severity of the disorder observed in individuals with 22q11.2 deletions can vary (discussed below), a parent may have gone without a diagnosis if the disorder is mild in them. When in doubt, the geneticist can test for the deletion in a blood sample using the same FISH test. If a parent is found to have the deletion, the geneticists will then turn their attention to others in the family who might have it too. These could include other children as well as the siblings and parents of the affected parent.

If the doctors decide that neither parent has 22q11.2 deletion syndrome, then the risk for others in the family including their other children (siblings of the child with the 22q11.2 deletion) is no greater than anyone else in the world, which is estimated between 1 in 2,000 to 1 in 4,000 births.

If a sibling of a child with 22q11.2 deletion does not have the deletion, then they cannot pass it along to their children. The 22q11.2 deletion syndrome does not skip generations.

If a parent has 22q11.2 deletion syndrome, what will their child who inherits the deletion be like?

Scientists are actively trying to figure out why the disease varies if the loss of the piece of chromosome 22 is the same, but we do not know at this point.

If my fetus has 22q11.2 deletion, what will he or she be like?

There is a lot of variability in the disease among patients with 22q11.2 deletions. This creates uncertainty about the status of a developing fetus if the amniocentesis reveals that there is a 22q11.2 deletion. Using ultrasound testing, specially trained obstetricians can look at the developing fetus and define certain aspects of the 22q11.2 disorders such as potential kidney abnormalities. Similarly, specially trained pediatric cardiologists can look carefully at the heart of a developing fetus in order to detect serious heart defects. Some of the milder heart defects that babies with 22q11.2 deletions might be born with are not readily seen with this test. Fortunately, the most serious heart defects can be seen in nearly all fetuses. Definition of the heart defects enables physicians and parents to plan properly for the remaining pregnancy and the care of the baby after birth.

Developmental delay/learning issues are an important concern for children with 22q11.2 deletions although many children with them have minimal or mild learning problems. At present, there are no tools for predicting this aspect of the 22q11.2 deletion disorders in fetuses or newborns.