DiGeorge syndrome

DiGeorge syndrome (also known as 22q11.2 deletion syndrome) predominantly results from a microdeletion in chromosome 22, which disrupts the development of the pharyngeal arches and pouches, and may also cause neurological, immunological, endocrinological, or cognitive deficits.

Classic presentation is a triad of cardiac anomalies, hypoplastic thymus, and hypocalcaemia, but clinical manifestations are highly variable, ranging from mild learning disabilities to the complete spectrum of congenital malformations. This phenotypic variability occurs despite a highly consistent genetic lesion.

Presenting signs and symptoms depend on age at diagnosis and the organ system affected.

Treatment modalities depend on clinical manifestations present in the individual patient. Management follows typical practice for patients without the syndrome, for any given feature.

DiGeorge syndrome, also known as 22q11.2 deletion syndrome (22q11.2DS) or velocardiofacial syndrome, is a condition that describes characteristic, but variable, morphological and neurological features that result from the deletion of one copy of 22q11.2.[1]McDonald-McGinn DM, Sullivan KE, Marino B, et al. 22q11.2 deletion syndrome. Nat Rev Dis Primers. 2015 Nov 19;1:15071. https://pmc.ncbi.nlm.nih.gov/articles/PMC4900471 http://www.ncbi.nlm.nih.gov/pubmed/27189754?tool=bestpractice.com ​ The classical presentation is a triad of cardiac anomalies, hypoplastic thymus, and hypocalcaemia (resulting from parathyroid hypoplasia). The deletion causes a reduction in TBX1, a key transcription factor for development of the pharyngeal arches.[2]Du Q, de la Morena MT, van Oers NSC. The genetics and epigenetics of 22q11.2 deletion syndrome. Front Genet. 2019;10:1365. https://pmc.ncbi.nlm.nih.gov/articles/PMC7016268 http://www.ncbi.nlm.nih.gov/pubmed/32117416?tool=bestpractice.com ​ This developmental disruption may cause cardiac anomalies, immunological abnormalities, cleft lip and palate, hypoparathyroidism, learning disabilities, and schizophrenia.[3]Cirillo A, Lioncino M, Maratea A, et al. Clinical manifestations of 22q11.2 deletion syndrome. Heart Fail Clin. 2022 Jan;18(1):155-64. http://www.ncbi.nlm.nih.gov/pubmed/34776076?tool=bestpractice.com ​ The disorder is notable for marked variation in the penetrance of the various features. The syndrome has been known by multiple other names, including CATCH22 and Shprintzen's syndromes. The complexity of the nomenclature is due to great variability in the clinical syndrome. 

The phenotype of DiGeorge syndrome may be divided into two components. The first, pharyngeal component consists of congenital heart disease, hypoplasia of the parathyroid glands, thymic hypoplasia with T-cell immunodeficiency, cleft lip and palate, and mild dysmorphic facial features. The second, neurological phenotype consists of mild cognitive dysfunction, which typically presents as learning disabilities, speech impairment, and an increased incidence of schizophrenia.[Figure caption and citation for the preceding image starts]: Loss of 1 copy of 22q11.2, demonstrated by microarray copy number analysisFrom the collections of Sean A. McGhee, MD and Maria Garcia Lloret, MD [Citation ends].