22q11.2 deletion syndrome

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22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population.

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Figure 1: Chromosome 22 idiogram.
Figure 2: Low copy repeats and genes within the 22q11.2 deletion.
Figure 3: 22q11.2 non-allelic homologous recombination.
Figure 4: Development of the cardiovascular and pharyngeal structures affected in 22q11.2 deletion syndrome.
Figure 5: Organ and system involvement in 22q11.2 deletion syndrome.
Figure 6: Craniofacial features associated with 22q11.2 deletion syndrome.
Figure 7: Developmental trajectory.
Figure 8: Associated autosomal recessive conditions on 22q11.2.


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The authors acknowledge grants from the National Institute of Mental Health (consortium grants U01MH101723, U01MH101720 and U01MH101719-01 to D.M.M.-M., N.P., A.S., J.A.S.V., B.S.E., J.R.V., B.E.M. and A.S.B., and grant U01MH087636 to D.M.M.-M.); NIH grant P01-HD070454 to D.M.M.-M., B.S.E. and B.E.M.; the Immune Deficiency Foundation, Baxalta and Janssen (to K.S.); Brain and Behavior Research Foundation (formerly NARSAD) 2010 Young Investigator Award (to J.A.S.V.); and the Canadian Institutes of Health Research (CIHR; MOP 97800 and MOP 111238), the Canada Research Chair in Schizophrenia Genetics and Genomic Disorders, and the Dalglish Chair in 22q11.2 Deletion Syndrome (to A.S.B.). The authors thank L. DiCairano, L. Lunny, A. Melchiorre, K. Schlechtweg, M. Torsan and G. Wong for assistance with manuscript formatting.

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Introduction (D.M.M.-M., K.E.S. and A.S.B.); Epidemiology (D.M.M.-M., K.E.S., B.M. and A.S.B.); Mechanisms/pathophysiology (D.M.M.-M., K.E.S., B.M., J.A.S.V., J.R.V., B.E.M., P.J.S. and A.S.B.); Diagnosis, screening and prevention (D.M.M.-M., K.E.S., B.M., N.P., A.S., J.A.S.V., E.H.Z., B.S.E. and A.S.B.); Management (D.M.M.-M., K.E.S., B.M., N.P., A.S., J.A.S.V., E.H.Z. and A.S.B.); Quality of life (D.M.M.-M., K.E.S., B.M., A.S., J.A.S.V. and A.S.B.); Outlook (D.M.M.-M., K.E.S., B.E.M, P.J.S., J.R.V. and A.S.B.); Overview of the Primer (D.M.M.-M.).

Correspondence to Donna M. McDonald-McGinn.

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D.M.M.-M. has presented lectures on 22q11.2 deletion syndrome for Natera. All other authors declare no competing interests.

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McDonald-McGinn, D., Sullivan, K., Marino, B. et al. 22q11.2 deletion syndrome. Nat Rev Dis Primers 1, 15071 (2015) doi:10.1038/nrdp.2015.71

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