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Chromosome 22q11.2 deletion syndrome is a common syndrome also known as DiGeorge syndrome and velocardiofacial syndrome. It occurs in approximately 1:4000 births, and the incidence is increasing due to affected parents bearing their own affected children. The manifestations of this syndrome cross all medical specialties, and care of the children and adults can be complex. Many patients have a mild to moderate immune deficiency, and the majority of patients have a cardiac anomaly. Additional features include renal anomalies, eye anomalies, hypoparathyroidism, skeletal defects, and developmental delay. Each child's needs must be tailored to his or her specific medical problems, and as the child transitions to adulthood, additional issues will arise. A holistic approach, addressing medical and behavioral needs, can be very helpful.