Which are the causes of 22q11 DiGeorge Syndrome?

22q11 DiGeorge Syndrome is caused by a submicroscopic deletion of a small segment of genetic material on chromosome 22, specifically at the q11.2 location. This missing piece of DNA contains approximately 30 to 40 genes that are essential for the normal development of various body systems, including the heart, palate, and immune system.

What is the underlying genetic cause of 22q11 DiGeorge Syndrome?

The primary cause of 22q11 DiGeorge Syndrome is a genetic anomaly known as a microdeletion. In approximately 90% of cases, this deletion occurs spontaneously (de novo) during the formation of reproductive cells or in early fetal development, meaning it is not inherited from either parent. In the remaining 10% of cases, the condition is inherited from an affected parent in an autosomal dominant pattern, meaning there is a 50% chance of passing the deletion to each child. The deleted region, often referred to as 22q11.2, contains genes such as TBX1, which is widely considered a key driver of the developmental abnormalities seen in patients with 22q11 DiGeorge Syndrome.

Are there environmental triggers or other risk factors?

Unlike some conditions that are influenced by external environmental factors, 22q11 DiGeorge Syndrome is purely a genetic event. There is no evidence to suggest that maternal behavior, diet, or environmental exposures during pregnancy cause the 22q11.2 deletion. It is important to distinguish between "causes" and "risk factors": the deletion is the definitive cause, while the risk factor for having a child with the condition is primarily the presence of the deletion in a parent’s genetic makeup. Because the deletion is microscopic, it is often missed on standard karyotype tests, which is why specialized genetic testing is required for diagnosis.

How do these genes affect body development?

The genes located within the deleted region of 22q11 DiGeorge Syndrome function like an architectural blueprint. When these specific instructions are missing, the body’s "construction crew" fails to properly build certain structures during the first few weeks of pregnancy. The following structures are frequently impacted due to the loss of these genetic instructions:

• The Heart: Structural defects such as tetralogy of Fallot or interrupted aortic arch.


• The Immune System: Underdevelopment of the thymus gland, leading to T-cell deficiencies.


• The Palate: Cleft palate or velopharyngeal insufficiency, which can affect speech and feeding.


• Calcium Regulation: Hypoparathyroidism, which can lead to dangerously low calcium levels in the blood.

Is the etiology of 22q11 DiGeorge Syndrome fully understood?

While we know the specific location of the deletion, researchers are still actively studying why the clinical presentation of 22q11 DiGeorge Syndrome varies so significantly between individuals. Even within the same family, one person might have severe heart defects while another has only mild learning differences. Current research is focused on "modifier genes"—other genetic variations elsewhere in the genome that may act as buffers or exacerbators of the missing 22q11.2 material. Understanding these pathways is the focus of ongoing work by the 215 members of our 22q11 DiGeorge Syndrome community and global research consortia.

Next steps

• Consult a clinical geneticist to discuss microarray testing if you suspect a diagnosis.


• Request a referral to a pediatric cardiologist and immunologist for comprehensive baseline screening.


• Connect with the 22q11 DiGeorge Syndrome community on DiseaseMaps.org to share experiences and find local support.


• Review your family history with a genetic counselor to understand inheritance risks for future pregnancies.

Medical disclaimer: This content is for informational purposes only and does not constitute medical advice, diagnosis, or treatment; always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition.

References

• NIH Genetic and Rare Diseases Information Center (GARD): 22q11.2 deletion syndrome.


• Orphanet: 22q11.2 deletion syndrome (ORPHA:567).


• OMIM (Online Mendelian Inheritance in Man): DiGeorge Syndrome (#188400).


• The International 22q11.2 Foundation.