DiGeorge Syndrome

DiGeorge syndrome, also known as 22q11.2 deletion syndrome, is the prototype of syndromes due to defective development of the third and fourth pharyngeal pouch. Even though the association between thymic aplasia and congenital hypoparathyroidism was first observed by Sedlackova in 1955 and Lobdell in 1959, only in 1965 were these signs classified as a new syndrome called DiGeorge (DGS) syndrome, from the name of Dr. Angelo DiGeorge, who reported a few infants with congenital absence of the thymus and parathyroid glands. Congenital heart disease (CHD), particularly involving the outflow tract, was later added to the list of the typical symptoms. However, the phenotypic spectrum of the syndrome is very wide (McDonald-McGinn and Sullivan 2011). The DGS phenotype, initially restricted to the presence of all or more than one of the above-mentioned signs, was extended over time even to patients with only a few classic symptoms, not necessarily associated with the presence of endocrine or immunological alterations, such as Velocardio Facial Syndrome or VCSF (MIM192430), or the Conotruncal Anomaly Face Syndrome (CTAFS)/Takao syndrome (MIM217095). VCFS has been defined as the association of palatoschisis, cardiac defects, typical facies, and difficulties in acquiring language and learning skills, while CTAFS is characterized by conotruncal cardiac defects and a peculiar facial appearance. The finding that 22q11.2 deletion can be detected in these subjects confirms that CTAFS, VCFS, and DGS are the same entity. A DGS phenotype may be also found in patients with diabetic or retinoic acid embryopathy and it has also been described in patients carrying mutations in the Chromodomain Helicase DNA-binding Protein 7 gene (CHD7), responsible for CHARGE syndrome, T-box 1 gene (TBX1), or other chromosomal alterations, including the 10p13-14, 11q23ter11, 3p12.3, 17p13, and 4q34.1q35.2 (Corsten-Janssen et al. 2013; Cirillo et al. 2017), suggesting that the biological differentiation process of the organs involved in the syndrome involves a very high number of genes, as expected. A different degree of immunological abnormalities has been described in all these conditions.