Immunologic Aspects of DiGeorge Syndrome

Abstract

After completing this article, readers should be able to: 1. Describe the immune defects seen in DiGeorge syndrome. 2. Review recommended immune testing and immune follow-up in patients with DiGeorge syndrome. 3. Review the indications for screening for DiGeorge syndrome. 4. Describe the variety of other congenital defects that can be associated with DiGeorge syndrome. 5. Review recommended anticipatory guidance for patients with DiGeorge syndrome. DiGeorge syndrome (DGS) is a contiguous field defect of the third and fourth pharyngeal pouches, most often due to a hemizygous microdeletion in the chromosome 22q11.2 region. Although classically defined as the triad of conotruncal cardiac anomaly, thymic hypoplasia, and hypocalcemia, the syndrome encompasses a broad spectrum of congenital defects that have varying degrees of severity. Speech delay and dysmorphic features are two of the most common and consistent findings. It shares phenotypic features with velocardiofacial syndrome, conotruncal anomaly face syndrome, Opitz-G syndrome, CHARGE syndrome, and cranio-cerebello-cardiac dysplasia syndrome. In some patients, these other syndromes are the result of the same 22q11.2 microdeletion and may represent variation in the presentation of DGS rather than separate syndromes. This review focuses on the immune defects seen in the patient population with hemizygous 22q11.2 microdeletion. The underlying defect of DGS is due to inadequate contribution of neural crest tissue to the third and fourth pharyngeal pouches that contribute to facial, cardiac, thymic, and parathyroid tissues. DGS can be caused by either genetic defects or environmental exposures in utero. Fetal exposure to ethanol, retinoids, and maternal diabetes can result in a clinical DGS phenotype. In more than 90% of patients, however, the syndrome results from hemizygosity at the chromosome 22q11.2 region (del22q11.2). In a small subset of patients, a deletion of 10p13 has been identified as the causative factor, as has monosomy 18q21.33 and trisomy 18. No genetic or environmental cause can be identified …