DiGeorge syndrome is a genetic condition caused by a small missing piece of chromosome 22 that disrupts the development of several body systems before birth. Also called 22q11.2 deletion syndrome, it affects roughly 1 in every 2,148 live births, making it the most common microdeletion syndrome in humans. The missing segment contains about 50 genes, and their absence can cause problems ranging from heart defects and immune deficiency to low calcium levels, learning difficulties, and distinct facial features.
What Causes the Deletion
The deletion occurs at a specific spot on chromosome 22 called the q11.2 region. In most cases it happens randomly, either in the father’s sperm, the mother’s egg, or very early in embryonic development. It is not typically inherited, and parents who don’t carry the deletion have no way to predict or prevent it. When someone who has the deletion has children, though, there is a 50 percent chance of passing it on.
Because the missing genes influence how multiple organs form during fetal development, DiGeorge syndrome doesn’t look the same in every person. One child may be born with a serious heart defect but normal calcium levels and only mild immune problems. Another may have no heart issues at all but significant low calcium and very few immune cells. This wide variability is one reason the condition often goes unrecognized.
Heart Defects
Heart problems are one of the hallmark features. About 75 to 80 percent of people with DiGeorge syndrome are born with some form of congenital heart defect. The most common types involve the large blood vessels leaving the heart: interrupted aortic arch, truncus arteriosus (where a single vessel exits the heart instead of two), and tetralogy of Fallot, a combination of four structural problems that reduces oxygen in the blood. Together, these three categories account for roughly 95 percent of the cardiac malformations seen in autopsy-confirmed cases. Many of these defects require surgical repair in infancy.
Immune System Problems
The thymus, a small organ behind the breastbone, is where immune cells called T cells mature. In DiGeorge syndrome the thymus is underdeveloped or, rarely, completely absent. Most people with the deletion have a partial reduction in T cells, which means they can still fight infections but may get sick more often or take longer to recover. Vaccines that contain live viruses may need to be delayed or avoided until a doctor confirms that T-cell function is adequate.
In a small subset of cases (sometimes called “complete” DiGeorge syndrome), the thymus is entirely missing and the immune system is severely compromised. These children are vulnerable to life-threatening infections and may require a thymus tissue transplant or a bone marrow transplant to rebuild immune function.
Low Calcium and Parathyroid Issues
The parathyroid glands, tiny structures in the neck that regulate calcium, are often underdeveloped or absent. Without enough parathyroid hormone, calcium levels in the blood drop. In newborns this can cause seizures, muscle twitching, or jitteriness. Some people develop low calcium only during periods of stress, illness, or surgery, while others need lifelong calcium and vitamin D supplementation to keep levels stable. About 50 to 60 percent of people with the deletion experience hypocalcemia at some point in their lives.
Facial Features and Palate Differences
Certain subtle facial characteristics are common: a bulbous nose, a small mouth, low-set ears, hooded eyelids, and a flat midface. These features can be mild enough that they go unnoticed by anyone who isn’t specifically looking for them. Cleft palate or, more often, a problem with the soft palate called velopharyngeal insufficiency (where the palate doesn’t close properly against the back of the throat during speech) affects a significant number of children. This can cause a nasal-sounding voice, difficulty feeding in infancy, and speech delays that benefit from early therapy.
Learning and Mental Health
Most children with DiGeorge syndrome have some degree of developmental delay, particularly in speech and language. IQ scores vary widely but tend to fall in the borderline-to-low-average range. Learning difficulties are common enough that early intervention with speech therapy, occupational therapy, and educational support makes a meaningful difference.
The psychiatric dimension is significant. In a study of 411 patients, about 13 percent developed a psychotic disorder such as schizophrenia, a rate far higher than the roughly 1 percent seen in the general population. Researchers found that a decline in verbal IQ scores became noticeable from around age 11 onward in children who later developed psychosis, and that a baseline IQ below 75 during childhood was an independent risk factor. Anxiety disorders, ADHD, and mood disorders are also more common. About 10 percent of people with the deletion develop autoimmune conditions, including thyroid disease (which affects up to 30 percent of adults), celiac disease, or autoimmune-related low platelet counts.
How It’s Diagnosed
DiGeorge syndrome is confirmed through genetic testing. For years the standard test was a technique called FISH (fluorescence in situ hybridization), which uses a fluorescent probe to check whether the specific region on chromosome 22 is present. FISH is still useful for screening family members or for prenatal testing when a deletion has already been identified in the family.
Increasingly, though, a broader test called a chromosomal microarray is preferred, especially in newborns in intensive care or in cases where clinical signs are ambiguous. Microarray testing scans the entire genome for missing or extra segments of DNA, so it can catch deletions that FISH might miss if they’re smaller or in an atypical location. For a baby born with a heart defect, seizures from low calcium, or unexplained immune deficiency, microarray testing is often ordered as a first step.
Treatment and Ongoing Care
There is no single treatment for DiGeorge syndrome because the condition affects so many systems. Instead, care is tailored to whichever problems are present. A child born with a critical heart defect will need cardiac surgery, sometimes within the first days or weeks of life. Low calcium is managed with supplements. Feeding and swallowing difficulties, which are common in infancy, may require specialized feeding techniques or therapy.
Because the needs are so varied, children do best when followed by a multidisciplinary team. This typically involves specialists in cardiology, immunology, endocrinology, speech pathology, genetics, and sometimes plastic surgery or ear-nose-throat medicine for palate issues. As children grow, the focus shifts toward managing learning difficulties, monitoring immune function, and watching for early signs of psychiatric conditions.
Long-Term Outlook
Many people with DiGeorge syndrome live into adulthood and beyond, especially when heart defects are repaired early and immune function is adequate. However, the deletion does carry a risk of premature death. In one long-term study following over 100 adults with the deletion, survival to age 40 was about 90 percent, dropping to roughly 74 percent by age 50. The median age at death among those who died during the study was 41.5 years.
The most striking finding was that sudden, unexplained death accounted for half of the deaths in that group, including in people whose heart defects had been repaired or who had no known heart disease at all. Other causes included pneumonia, stroke, and complications of existing heart conditions. These numbers underscore why ongoing cardiac monitoring remains important even in adults who feel well. With coordinated medical care and early support for developmental and psychiatric needs, many people with DiGeorge syndrome lead independent, fulfilling lives.