The DiGeorge anomaly.

Abstract

The DiGeorge anomaly, originally considered a clinical paradigm for isolated thymus deficiency, has now been redefined as a member of a group of disorders that share in common a chromosome deletion resulting in monosomy 22q11 (CATCH-22 or DGA/VCFS). In addition to the thymus defect, conotruncal heart anomalies, dysmorphism, hypoparathyroidism, and cleft palate are prominent features. Despite the emphasis on thymus involvement in DGA, a clinically significant thymus defect is found only in a small percentage of these patients probably occurring in less than 5% of the cases. Maldescent of the thymus, however, is extremely common, leading to an absence of mediastinal thymic tissue in nearly all cases. The basic embryological fault in these disorders is an inadequate development of the facial neural-crest tissues, resulting in defective organogenesis of pharyngeal pouch derivatives that receive cephalic neural-crest contribution to the mesenchmyme. The causes for this maldevelopment are both genetic and extragenetic in origin and the genetic lesions act in concert with random environmental events to produce the ultimate clinical picture. The modern research approaches now available have cleared away most of the confusion clouding the clinical and theoretical aspects of DGA and related disorders, providing the clinician with useful landmarks to assess and treat these intriguing clinical challenges.