DiGeorge AM, editor. Congenital absence of the thymus and its immunologic consequences: concurrence with congenital hypothyroidism. Birth defects. Vol IV(1). White Plains, New York: March of Dimes-Birth Defects Foundation, 1968.

Davies EG. Immunodeficiency in DiGeorge syndrome and options for treating cases with complete athymia. Front Immunol. 2013;4:322. https://doi.org/10.3389/fimmu.2013.00322.

Article  CAS  PubMed  PubMed Central  Google Scholar 

•• Mustillo PJ, Sullivan KE, Chinn IK, et al. Clinical practice guidelines for the immunological management of chromosome 22q11.2 deletion syndrome and other defects in thymic development. J Clin Immunol. 2023;43(2):247–70. https://doi.org/10.1007/s10875-022-01418-y. This recent article provides guidelines for initial and longitudinal assessment of immunologic status in 22q11.2DS. The article also reviews the common immunologic findings in 22q11.2DS and the genetic and non-genetic causes of DGS.

Shearer WT, Rosenblatt HM, Gelman RS, et al. Lymphocyte subsets in healthy children from birth through 18 years of age: the Pediatric AIDS Clinical Trials Group P1009 study. J Allergy Clin Immunol. 2003;112(5):973–80. https://doi.org/10.1016/j.jaci.2003.07.003.

Article  PubMed  Google Scholar 

Driscoll DA, Salvin J, Sellinger B, et al. Prevalence of 22q11 microdeletions in DiGeorge and velocardiofacial syndromes: implications for genetic counselling and prenatal diagnosis. J Med Genet. 1993;30(10):813–7. https://doi.org/10.1136/jmg.30.10.813.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Katzman PJ, Smoot LB, Cox GF. Cardiac registry screening for DiGeorge critical region deletion using loss of heterozygosity analysis. Pediatr Dev Pathol. 2006;9:266–79.

Article  CAS  PubMed  Google Scholar 

Rope AF, Cragun DL, Saal HM, Hopkin RJ. DiGeorge anomaly in the absence of chromosome 22q11.2 deletion. J Pediatr. 2009;155(4):560–5. https://doi.org/10.1016/j.jpeds.2009.04.010.

Article  CAS  PubMed  Google Scholar 

Campbell IM, Sheppard SE, Crowley TB, et al. What is new with 22q? An update from the 22q and You Center at the Children’s Hospital of Philadelphia. Am J Med Genet A. 2018;176(10):2058–69. https://doi.org/10.1002/ajmg.a.40637.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Calmont A, Ivins S, Van Bueren KL, et al. Tbx1 controls cardiac neural crest cell migration during arch artery development by regulating Gbx2 expression in the pharyngeal ectoderm. Development. 2009;136(18):3173–83. https://doi.org/10.1242/dev.028902.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sulik KK, Johnston MC, Daft PA, Russell WE, Dehart DB. Fetal alcohol syndrome and DiGeorge anomaly: critical ethanol exposure periods for craniofacial malformations as illustrated in an animal model. Am J Med Genet Suppl. 1986;2:97–112. https://doi.org/10.1002/ajmg.1320250614.

Article  CAS  PubMed  Google Scholar 

Ammann AJ, Wara DW, Cowan MJ, Barrett DJ, Stiehm ER. The DiGeorge syndrome and the fetal alcohol syndrome. Am J Dis Child. 1982;136(10):906–8.

CAS  PubMed  Google Scholar 

Coberly S, Lammer E, Alashari M. Retinoic acid embryopathy: case report and review of literature. Pediatr Pathol Lab Med. 1996;16(5):823–36.

Article  CAS  PubMed  Google Scholar 

Cirillo E, Giardino G, Gallo V, et al. DiGeorge-like syndrome in a child with a 3p12.3 deletion involving MIR4273 gene born to a mother with gestational diabetes mellitus. Am J Med Genet A. 2017;173(7):1913–8. https://doi.org/10.1002/ajmg.a.38242.

Article  CAS  PubMed  Google Scholar 

Wilson TA, Blethen SL, Vallone A, et al. DiGeorge anomaly with renal agenesis in infants of mothers with diabetes. Am J Med Genet. 1993;47(7):1078–82. https://doi.org/10.1002/ajmg.1320470729.

Article  CAS  PubMed  Google Scholar 

Roberts C, Ivins SM, James CT, Scambler PJ. Retinoic acid down-regulates Tbx1 expression in vivo and in vitro. Dev Dyn. 2005;232(4):928–38. https://doi.org/10.1002/dvdy.20268.

Article  CAS  PubMed  Google Scholar 

• Du Q, de la Morena MT, van Oers NSC. The genetics and epigenetics of 22q11.2 deletion syndrome. Front Genet. 2020;10:1365. Published 2020 Feb 6. https://doi.org/10.3389/fgene.2019.01365. This article reviews the genetic origins of 22q11.2DS and the pathogenesis of disease, which helps to explain the variability in phenotype.

Greenberg F, Courtney KB, Wessels RA, et al. Prenatal diagnosis of deletion 17p13 associated with DiGeorge anomaly. Am J Med Genet. 1988;31(1):1–4. https://doi.org/10.1002/ajmg.1320310102.

Article  CAS  PubMed  Google Scholar 

Cirillo E, Prencipe MR, Giardino G, et al. Clinical phenotype, immunological abnormalities, and genomic findings in patients with DiGeorge spectrum phenotype without 22q11.2 deletion. J Allergy Clin Immunol Pract. 2020;8(9):3112–20. https://doi.org/10.1016/j.jaip.2020.06.051.

Article  PubMed  Google Scholar 

Fernández L, Lapunzina P, Pajares IL, et al. Unrelated chromosomal anomalies found in patients with suspected 22q11.2 deletion. Am J Med Genet A. 2008;146A(9):1134–41. https://doi.org/10.1002/ajmg.a.32256.

Article  PubMed  Google Scholar 

Gottlieb S, Driscoll DA, Punnett HH, Sellinger B, Emanuel BS, Budarf ML. Characterization of 10p deletions suggests two nonoverlapping regions contribute to the DiGeorge syndrome phenotype. Am J Hum Genet. 1998;62(2):495–8. https://doi.org/10.1086/301718.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Koczkowska M, Wierzba J, Śmigiel R, et al. Genomic findings in patients with clinical suspicion of 22q11.2 deletion syndrome. J Appl Genet. 2017;58(1):93–8. https://doi.org/10.1007/s13353-016-0366-1.

Article  CAS  PubMed  Google Scholar 

Snijders Blok C, Corsten-Janssen N, FitzPatrick DR, et al. Definition of 5q11.2 microdeletion syndrome reveals overlap with CHARGE syndrome and 22q11 deletion syndrome phenotypes. Am J Med Genet A. 2014;164A(11):2843–8. https://doi.org/10.1002/ajmg.a.36680.

Article  CAS  PubMed  Google Scholar 

Jyonouchi S, McDonald-McGinn DM, Bale S, Zackai EH, Sullivan KE. CHARGE (coloboma, heart defect, atresia choanae, retarded growth and development, genital hypoplasia, ear anomalies/deafness) syndrome and chromosome 22q11.2 deletion syndrome: a comparison of immunologic and nonimmunologic phenotypic features. Pediatrics. 2009;123(5):e871–7. https://doi.org/10.1542/peds.2008-3400.

Article  PubMed  Google Scholar 

Corsten-Janssen N, Saitta SC, Hoefsloot LH, et al. More clinical overlap between 22q11.2 deletion syndrome and CHARGE syndrome than often anticipated. Mol Syndromol. 2013;4(5):235–45. https://doi.org/10.1159/000351127.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Jawad AF, McDonald-Mcginn DM, Zackai E, Sullivan KE. Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Pediatr. 2001;139(5):715–23. https://doi.org/10.1067/mpd.2001.118534.

Article  CAS  PubMed  Google Scholar 

Sullivan KE, McDonald-McGinn D, Driscoll DA, Emanuel BS, Zackai EH, Jawad AF. Longitudinal analysis of lymphocyte function and numbers in the first year of life in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Diagn Lab Immunol. 1999;6(6):906–11. https://doi.org/10.1128/CDLI.6.6.906-911.1999.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chinen J, Rosenblatt HM, Smith EO, Shearer WT, Noroski LM. Long-term assessment of T-cell populations in DiGeorge syndrome. J Allergy Clin Immunol. 2003;111(3):573–9. https://doi.org/10.1067/mai.2003.165.

Article  PubMed  Google Scholar 

• Giardino G, Radwan N, Koletsi P, et al. Clinical and immunological features in a cohort of patients with partial DiGeorge syndrome followed at a single center. Blood. 2019;133(24):2586–96. https://doi.org/10.1182/blood.2018885244. This recent article provides clinical and immunological data from a large clinical cohort of patients that helps to identify risk factors for infections, atopy, and autoimmunity.

Article  CAS  PubMed  Google Scholar 

Ferrando-Martínez S, Lorente R, Gurbindo D, et al. Low thymic output, peripheral homeostasis deregulation, and hastened regulatory T cells differentiation in children with 22q11.2 deletion syndrome. J Pediatr. 2014;164(4):882–9. https://doi.org/10.1016/j.jpeds.2013.12.013.

Article  CAS  PubMed  Google Scholar 

Tantibhaedhyangkul U, Davis CM, Noroski LM, Hanson IC, Shearer WT, Chinen J. Role of IL-7 in the regulation of T-cell homeostasis in partial DiGeorge syndrome. J Allergy Clin Immunol. 2009;123(4):960-2.e2. https://doi.org/10.1016/j.jaci.2009.01.002.

Article  CAS  PubMed  Google Scholar 

Piliero LM, Sanford AN, McDonald-McGinn DM, Zackai EH, Sullivan KE. T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome. Blood. 2004;103(3):1020–5. https://doi.org/10.1182/blood-2003-08-2824.

Article  CAS  PubMed  Google Scholar 

•• Framme JL, Lundqvist C, Lundell AC, et al. Long-term follow-up of newborns with 22q11 deletion syndrome and low TRECs. J Clin Immunol. 2022;42(3):618–33. https://doi.org/10.1007/s10875-021-01201-5. This article details persistent immunologic aberrations in a subset of patients with 22q11.2DS, which emphasizes the role of expert immunologic evaluation and the importance of continued monitoring.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Morsheimer M, Brown Whitehorn TF, Heimall J, Sullivan KE. The immune deficiency of chromosome 22q11.2 deletion syndrome. Am J Med Genet A. 2017;173(9):2366–72. https://doi.org/10.1002/ajmg.a.38319.

Article  CAS  PubMed  Google Scholar 

Crowley B, Ruffner M, McDonald McGinn DM, Sullivan KE. Variable immune deficiency related to deletion size in chromosome 22q11.2 deletion syndrome. Am J Med Genet A. 2018;176(10):2082–6. https://doi.org/10.1002/ajmg.a.38597.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Sullivan KE, Jawad AF, Randall P, et al. Lack of correlation between impaired T cell production, immunodeficiency, and other phenotypic features in chromosome 22q11.2 deletion syndromes. Clin Immunol Immunopathol. 1998;86(2):141–6. https://doi.org/10.1006/clin.1997.4463.

Article  CAS  PubMed  Google Scholar 

Sullivan KE, Crowley TB, Maurer K, et al. T-cell lymphopenia in 22q11.2 deletion syndrome: Relationship to cardiac disease. J Allergy Clin Immunol Pract. 2018;6(2):690–1. https://doi.org/10.1016/j.jaip.2017.08.028.

Article  PubMed