Patients with this syndrome demonstrate marked variability in their immune system, ranging from complete thymic aplasia to reduced T-cell counts and function. The majority of patients (~75%) have a decrease in the total number of T cells, and approximately 1.5% of patients have complete thymic aplasia requiring transplant. Reduced levels of immunoglobulin A (IgA) and immunoglobulin M (IgM) also occur more frequently compared to the general population. Almost all patients have a tendency toward infection, particularly of the respiratory tract. As long as there is a working thymus, patients with 22q11 deletion syndrome can be immunized and generate a good antibody response because humoral immunity is usually intact. However, poor vaccine-specific antibody responses have been described. Neonatal diagnosis historically relied on fluorescence in situ hybridization (FISH) testing and phenotype recognition. However, T-cell receptor excision circles (TRECs) and polymerase chain reaction (PCR) testing are now included in the newborn screening panel for severe combined immunodeficiency (SCID). This allows for early identification of 22q11.2 deletion syndrome patients with severe T-cell lymphopenia. In addition, cell-free DNA from maternal serum might help identify these patients in utero. Autoimmune conditions are found in up to a third of patients, the most common being juvenile chronic arthritis, autoimmune thrombocytopenia, hemolytic anemia, Raynaud phenomena, and autoimmune thyroid disease.

References

• Kuo CY, Signer R, Saitta SC. Immune and genetic features of chromosome 22q11.2 deletion (DiGeorge syndrome). Curr Allergy Asthma Rep. 2018;18:75.
• Sullivan KE. Chromosome 22q11.2 deletion syndrome and DiGeorge syndrome. Immunol Rev. 2019;287: 186-201.
• Urschel D, Hernandez-Trujillo VP. Spectrum of genetic T-cell disorders from 22q11.2DS to CHARGE. Clin Rev Allergy Immunol. 2022;63:99-105.