**3.1.1 DiGeorge syndrome: Defective thymic development**

DiGeorge syndrome is a congenital malformation involving defective development of the structures derived from the third and fourth pharyngeal pouch during fetal life, as thymus and parathyroid glands, among others. Depending on the severity of the syndrome, thymus can be completely absent or just reduced or misplaced. When thymus is present, thymic structure and functionality, despite reduced, is normal. Approximately 90% of all DiGeorge syndromes present a specific deletion on the region q11.2 of chromosome 22, while the remaining 10% show other chromosomic defects due to gestational diabetes, fetal alcoholism syndrome or prenatal exposure to Accutane® (cystic acne treatment). A similar defect in thymic development has been reported when mutation in gene T box 1 (TBX1) occurs. Principal characteristics of the DiGeorge syndrome are shown in Table 2.


Table 2. Clinical features of DiGeorge syndrome.

Most urgent treatment for children with DiGeorge syndrome is *Pneumocistiis jirovenci* prophylaxis. General care includes treating hypocalcemia and correcting cardiac abnormalities. When TL immunity is severely compromised, thymus and bone marrow transplant can partially restore the adaptive immune system. Severe syndromes usually lead to sudden or cardiac-derived death. Surprisingly, less severe syndromes, where TL are reduced but not absent, natural improvement due to regrowth of remaining thymic tissue, extra-thymic TL maturation or ectopic thymus development can be observed.
