Defects in Thymic Development: DiGeorge/CHARGE/Chromosome 22q11.2 Deletion
DiGeorge anomaly is characterized by defects of the heart, thymus, and parathyroid. To make the diagnosis of DiGeorge anomaly, two of the three organs must be affected. The genetic and syndromic associations with DiGeorge anomaly include 22q11.2 deletion syndrome, CHARGE (coloboma, heart defects, atresia of the choanae, retardation of growth and development, genital hypoplasia, ear anomalies and/or deafness) syndrome, and diabetic embryopathy. Most infants with DiGeorge anomaly have a small thymus resulting in low T cell numbers. Less than 1% of infants with DiGeorge anomaly are athymic and consequently have no thymically-derived T cells. This condition is "complete" DiGeorge anomaly. These infants are at high risk for life-threatening infections. Some infants with complete DiGeorge anomaly may develop an atypical phenotype similar to Omenn syndrome, with circulating oligoclonal T cells and severe rash. The symptoms leading to the diagnosis of DiGeorge anomaly and the management of these patients are described in this chapter.