DiGeorge syndrome is a set of birth defects that include problems with an immune system organ called the thymus, the parathyroid glands, and the heart. Infants born with this condition may also have a structural problem in the roof of the mouth called a cleft palate and are at elevated risk for various mental disorders. Often, the name DiGeorge syndrome is used interchangeably with “22q11.2 deletion syndrome”, but technically there are a variety of similar conditions falling into the category of “22q11.2 deletion syndrome”. Of these conditions, DiGeorge syndrome is the most widely known, but it is fairly rare, striking about 1 in 4,000 newborns, and generally the doctors and parents will be aware of it prior to birth.
The term “22q11.2 deletion” refers to what geneticists call a microdeletion, meaning that part of a particular chromosome is missing. Specifically, there is a microdeletion on the long arm of chromosome number 22, which is one of 23 chromosomes present in your body cells, each in two copies, meaning that there are 23 pair of chromosomes, or a total of 46. Absence of part of the long arm of chromosome 22 means that such children are missing certain genes —genes that are located in that missing region of the chromosome. In fact, children with this disorder typically are missing about 30-40 genes. There is variation in how many and which genes are missing, so there is variation on how the form and severity that DiGeorge syndrome takes. To suffer the disorder, the abnormality need only occur on one of the two chromosomes of pair number 22. In other words, one of the child’s chromosome 22 can be perfectly normal, while the other one is abnormal for DiGeorge and the child will have the condition. This is called a dominant genetic disorder. Although only around 10 percent of cases are inherited parents passing down the condition, having one parent with the condition is enough for the child to be affected. Meanwhile, in 90 percent of cases, the deletion on chromosome 22 occurs spontaneously, meaning not inherited from either parent. But the fact that the deletion need only occur on one of the two copies of chromosome 22 also makes the condition a dominant genetic disorder, since the child can grow up and pass it down to his or her children, also with dominant inheritance.
As for what those missing genes do, that’s the hard part. Scientists are not certain about what many of the missing genes even do, but they do know a lot about some of them. One gene, called TBX1, for instance, is thought to be important when it comes to most physical symptoms, such as the cleft palate and heart abnormalities. Also, a gene called COMT may be at center stage, when it comes to and mental illness and behavior. In most cases, the deletion of part of the long arm of chromosome 22 happens randomly. There may be some maternal factors that can put the baby at risk for DiGeorge syndrome to develop by causing the deletions, but the full story is not very clear. Some evidence suggests that maternal alcohol consumption at levels high enough to cause fetal alcohol syndrome may be responsible for some of the cases.
As noted earlier, DiGeorge syndrome classically affects the thymus. This is a kind of lymphatic organ located in the chest, that shrinks from infancy onward. The thymus is part of the immune system. It is a place where a type of white blood cells, called T-lymphocytes develop. These are immune cells that fight against infection and the thymus gland produces most of them even prior to birth. In DiGeorge syndrome, the thymus is either extremely undeveloped, or is absent, so the child is very susceptible to infections. Also, in DiGeorge syndrome, the parathyroid glands do not develop. These are tiny glands that are embedded within the thyroid gland. The job of the parathyroids is to increase the level of calcium in the blood whenever the level of calcium drops too low. Consequently, babies with DiGeorge syndrome have hypocalcemia, meaning low levels of calcium in the blood. In infants, this can cause rapid heartbeats and rapid breathing or cessation of breathing, poor feeding, the jitters, tetany, muscle spasms, and seizures.
Congenital heart abnormalities that can develop as a result of DiGeorge syndrome include the cyanotic type, meaning the kind of congenital heart disease in which the infant turns blue, due to large amounts of blood that has not passed through the lungs getting shunted into the systemic circulation. Such conditions include truncus arteriosus, of which one in three cases are due to DiGeorge syndrome. Other cyanotic congenital heart conditions commonly associated with DiGeorge syndrome of tetralogy of Fallot and transposition of the great vessels. All of these heart malformations also are associated with health problems in the mothers, notably pre-gestational diabetes, poor nutrition, and rubella.