22q11 Deletion Syndrome
22q11 Deletion Syndrome (22qDS), which is also known as velocardiofacial syndrome or DiGeorge syndrome, has multiple possible features, including: learning difficulties, speech or palate problems, characteristic but subtle facial features, congenital (present at birth) cardiac (heart) defects, other birth defects (e.g., foot deformities), hypocalcemia (low calcium levels in the
blood). Because the physical features are often subtle and the condition is not yet well known, 22qDS is under-recognized, especially in adults. We have developed screening criteria to help doctors and other clinicians better recognize 22qDS. 22qDS may be definitively diagnosed using specialized chromosomal testing called Fluorescence In-Situ Hybridization ("FISH") (see Figure 1).
22qDS is associated with a chromosomal abnormality, a small deletion on chromosome 22q11.2. (see Figure 1)There are dozens of genes in the deleted region on chromosome 22, but specific causative genes for 22qDS have not yet been identified. 22qDS occurs in about 1 in 2,000 to 1 in 4,000 births. This means 22qDS is more common then other conditions like Huntington's Disease and Duchenne Muscular Dystrophy.
One of our main research studies involves adults with tetralogy of Fallot (TOF) and other congenital heart defects. Patients born with TOF have about a 15% (about 1 in 7) chance of having 22qDS. The special blood test (FISH) for 22qDS has only been available since about 1994, so many adults with TOF and other congenital heart defects have not yet been diagnosed. At the Toronto Congenital Cardiac Centre for Adults at the Toronto General Hospital we are screening several hundred adults for 22qDS and other genetic syndromes that may be associated with congenital heart defects. We are collaborating with Dr. Gary Webb, Dr. Jack Colman, Dr. Vera Rose, and the many other cardiologists at the clinic.
Our screening has doubled the rate of identifying patients with 22qDS at the
clinic.
In our study with patients at the Toronto Congenital Cardiac Centre for Adults we will be able to learn if there are certain features that people with a 22qDS subtype of congenital heart defect have that are more common or less common than others with the same congenital heart defect. For example, patients with 22qDS and TOF may have more pulmonary artery problems than patients with TOF that is not associated with 22qDS.
Why is it important to diagnose 22qDS?
There are two major reasons: prevention and early detection of serious illnesses, and genetic counselling. There are important treatable illnesses associated with 22qDS that may develop at any age and that doctors can watch for. Hypocalcemia (low calcium) can develop at any age in 22qDS and may lead to seizures if not diagnosed and treated. Thyroid disease can also be associated with 22qDS.
Psychiatric illnesses can significantly interfere with functioning. All of
these illnesses are treatable, especially if they are caught early. This is preventive health care.
We recommend yearly monitoring of ionized calcium levels, parathyroid hormone (important for regulating calcium levels), and thyroid stimulating hormone levels. These are all simple blood tests. Similarly, symptoms of psychiatric illnesses, such as changes in behaviour and mood, can be watched out for (there are no blood tests for psychiatric illnesses). As we follow adults with 22qDS over time we will learn more about other conditions to watch out for.
The other major reason to diagnose 22qDS is for genetic counselling. Patients with 22qDS have a 50% (1 in 2) chance of passing the chromosome 22 deletion to each child they have (that is, at each pregnancy). Fertility is not usually affected in 22qDS so this is important information for individuals in their child-bearing years to have. Genetic counselling is an essential part of the clinical care of everyone with 22qDS.
Origin of the chromosome 22q deletion
About 90% of cases of 22qDS are sporadic (the individual is the first person in the family to have 22qDS). The mechanism of how and why this sporadic or "de novo" (spontaneously arising) deletion occurs is not known but we do know that it is nothing the parents did or did not do that caused the deletion. It is a chance occurrence.
In the other 10% of cases, one of the parents has 22qDS and has passed it on to their child. Because the physical findings associated with 22qDS can be quite subtle and vary from one person to the next, often a parent does not know that they have 22qDS until their child is diagnosed and they have been tested.
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Sometimes a person may have features of 22qDS but does not have a detectable deletion on chromosome 22. These patients may still have 22qDS but with a different genetic change than the one usually found. One of the goals of our research study is to define the spectrum of presentation of 22qDS in adults and to find out what these other genetic changes may be in some of our patients.
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Possible brain changes
There is some evidence that there may be visible changes in the brains of individuals with 22qDS. The underlying mechanisms causing these brain changes are not yet fully understood. It is also not yet known what percentage of individuals with 22qDS may have these changes, when they occur (e.g. before birth or later) and what role they may or may not play, for example, in specific learning difficulties. To help answer some of these research questions, we are inviting individuals with 22qDS to have Magnetic Resonance Imaging (MRI) done as part of our research initiative. MRI provides a detailed 3-dimensional picture of the brain without exposing the individual to radiation.
Goals of our 22qDS research
The overall goals of our research on 22qDS include gaining an understanding of the longterm health outcome for individuals with this syndrome. This is information that is not currently available, since most research until now has focussed only on children with 22qDS. Of particular interest to us are the psychiatric aspects of the syndrome. We hope to learn more about why individuals with this genetic condition may be at increased risk for psychiatric illnesses (e.g. anxiety or schizophrenia), and why some individuals with the deletion develop psychiatric aspects of the syndrome while others do not. Through the knowledge that we gain, we hope to be able to contribute to developing the best treatments for individuals with 22qDS and psychiatric illness.
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