Velo-cardio-facial syndrome (VCFS) is one of a number of syndromes which are associated with monosomic deletions of chromosome 22q11.2. In the older child, school issues are common and the physician can often provide insight into the optimal learning environment for the child; however, this seldom is affected by the presence of immunodeficiency. The immunodeficiency does not correlate with any other clinical feature. This makes it difficult to determine which infants should be screened for immunodeficiency. The most conservative approach would be to perform simple screening studies for T-cell defects. Infants suspected of having VCFS/chromosome 22q11.2 deletion syndrome should have FISH analyses performed. The 22q11.2 deletion and the 10p deletion should be sought and can be tested simultaneously. Humoral immunity should be assessed in patients with recurrent infections. Although chromosome 22q11.2 deletion syndrome is classically considered a T-cell defect, there may be secondary antibody deficits.