Skip to main content

Advertisement

Log in

Immune and Genetic Features of the Chromosome 22q11.2 Deletion (DiGeorge Syndrome)

  • Immune Deficiency and Dysregulation (DP Huston and C Kuo, Section Editors)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review provides an update on the progress in identifying the range of immunological dysfunction seen in DiGeorge syndrome and on more recent diagnostic and treatment approaches.

Recent Findings

Clinically, the associated thymic hypoplasia/aplasia is well known and can have profound effects on T cell function. Further, the humoral arm of the immune system can be affected, with hypogammaglobulinemia and poor vaccine-specific antibody response. Additionally, genetic testing utilizing chromosomal microarray demonstrates a small but significant number of 22q11 deletions that are not detectable by standard FISH testing. The recent addition of a TREC assay to newborn screening can identify a subset of infants whose severe immune defects may result from 22q11 deletion. This initial presentation now also places the immunologist in the role of “first responder” with regard to diagnosis and management of these patients.

Summary

DiGeorge syndrome reflects a clinical phenotype now recognized by its underlying genetic diagnosis, chromosome 22q11.2 deletion syndrome, which is associated with multisystem involvement and variable immune defects among patients. Updated genetic and molecular techniques now allow for earlier identification of immune defects and confirmatory diagnoses, in this disorder with life-long clinical issues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Greenberg F. DiGeorge syndrome: an historical review of clinical and cytogenetic features. J Med Genet. 1993;30:803–6.

    Article  CAS  Google Scholar 

  2. DiGeorge AM. Congenital absence of the thymus and its immunologic consequences: concurrence with congenital hypoparathyroidism. March of Dimes Birth Defects Foundation IV 1968; 116–121.

  3. Lischner HW. DiGeorge syndrome(s). Pediatrics. 1972;81:1042–4.

    Article  CAS  Google Scholar 

  4. Bejjani BA, Shaffer LG. Clinical utility of contemporary molecular cytogenetics. Ann Rev Genomics Hum Genet. 2008;9:71–86.

    Article  CAS  Google Scholar 

  5. •• McDonald-McGinn DM, Sullivan KE, Marino B, Philip N, Swillen A, Vorstman JAS, et al. 22q11.2 deletion syndrome. Nat Rev Dis Prim 2015; no. 15072. This article reviews the pathogenesis of the most frequent microdeletion syndrome encountered in human disease, including its genetic, molecular and embryologic origins. Further, clinical insights provide the reader with guidance on clinical management of patients.

  6. 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 https://doi.org/10.1002/ajmg.a.38597. [Epub ahead of print].

    Article  CAS  Google Scholar 

  7. Emanuel BS, Shaikh TH. Segmental duplications: an “expanding” role in genomic instability and disease. Nat Rev Genet. 2001;2:791–800.

    Article  CAS  Google Scholar 

  8. Emanuel BS, Saitta SC. From microscopes to microarrays: dissecting recurrent chromosomal rearrangements. Nat Rev Genet. 2007;8:869–83.

    Article  CAS  Google Scholar 

  9. Emanuel BS, McDonald-McGinn D, Saitta SC, Zackai EH. The 22q11.2 deletion syndrome. Adv Pediatr. 2001;48:39–73.

  10. Grati FR, Molina Gomes D, Ferreira JC, Dupont C, Alesi V, Gouas L, et al. Prevalence of recurrent pathogenic microdeletions and microduplications in over 9500 pregnancies. Prenat Diagn. 2015;35:801–9.

    Article  Google Scholar 

  11. • Bassett AS, McDonald-McGinn DM, Devriendt K, Digilio MC, Goldenberg P, Habel A, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159:332–9. These guidelines developed by a large international consortium of experts, provide a clinical checklist with helpful tables to approach patient care issues at multiple ages.

    Article  Google Scholar 

  12. Davies EG. Immunodeficiency in DiGeorge syndrome and options for treating cases with complete athymia. Front Immunol. 2013;4:1–9.

    Article  CAS  Google Scholar 

  13. •• Morsheimer M, Brown Whitehorn TF, Heimall J, Sullivan KE. The immune deficiency of chromosome 22q11.2 deletion syndrome. Am J Med Genet A. 2017;173:2366–72. This recent article is among the first to comprehensively outline the range of immune dysfunction encountered by patients with this genomic disorder and provides data based on experience derived from one of the largest clinical cohort of patients.

    Article  CAS  Google Scholar 

  14. Sullivan KE. Chromosome 22q11.2 deletion syndrome: DiGeorge syndrome/velocardiofacial syndrome. Immun All Clin N Am. 2008;28:353–66.

    Article  Google Scholar 

  15. Herwadkar A, Gennery AR, Moran AS, Haeney MR, Arkwright PD. Association between hypoparathyroidism and defective T cell immunity in 22q11.2 deletion syndrome. J Clin Path. 2010;63:151–5.

    Article  CAS  Google Scholar 

  16. Davies EG, Cheung M, Gilmour K, Maimaris J, Curry J, Furmanski A, et al. Thymus transplantation for complete DiGeorge syndrome: European experience. J Allerg Clin Immunol. 2017;140:1660–70.

    Article  CAS  Google Scholar 

  17. Finocchi A, Di Cesare S, Romiti ML, Capponi C, Rossi P, Carsetti R, et al. Humoral immune responses and CD27+ B cells in children with DiGeorge syndrome (22q11.2 deletion syndrome). Ped Aller Immunol. 2006;17:382–8.

    Article  CAS  Google Scholar 

  18. Jawad AF, Prak EL, Boyer J, McDonald-McGinn DM, Zackai E, McDonald K, et al. A prospective study of influenza vaccination and a comparison of immunologic parameters in children and adults with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Clin Immunol. 2011;31:927–35.

    Article  CAS  Google Scholar 

  19. Patel K, Akhter J, Kobrynski L, Gathman B, Davis O, Sullivan KE. Immunoglobulin deficiencies: the B-lymphocyte side of DiGeorge syndrome. J Pediatr. 2012;161:950–3.

    Article  CAS  Google Scholar 

  20. Smith CA, Driscoll DA, Emanuel BS, DM MD-MG, Zackai EH, Sullivan KE. Increased prevalence of immunoglobulin A deficiency in patients with the chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Diag Lab Immunol. 1998;5:415–7.

    CAS  Google Scholar 

  21. Derfalvi B, Maurer K, McDonald McGinn DM, Zackai E, Meng W, Luning Prak ET, et al. B cell development in chromosome 22q11.2 deletion syndrome. Clin Immunol. 2016;163(1–9):1–9.

    Article  CAS  Google Scholar 

  22. Kwan A, Church JA, Cowan MJ, Agarwal R, Kapoor N, Kohn DB, et al. Newborn screening for severe combined immunodeficiency and T-cell lymphopenia in California: results of the first 2 years. J Allerg Clin Immunol. 2013;132:140–50.

    Article  Google Scholar 

  23. Barry JC, Crowley TB, Jyonouchi S, Heimall J, Zackai EH, Sullivan KE, et al. Identification of 22q11.2 deletion syndrome via newborn screening for severe combined immunodeficiency. J Clin Immunol. 2017:1–10.

  24. Land MH, Garcia-Lloret MI, Borzy MS, Rao PN, Aziz N, McGhee SA et al. Long-term results of bone marrow transplantation in complete DiGeorge syndrome. J Allerg Clin Immunol. 2007; 120: 2007908–915, 908.

    Article  CAS  Google Scholar 

  25. McGhee SA, Lloret MG, Stiehm ER. Immunologic reconstitution in 22q deletion (DiGeorge) syndrome. Immunol Res. 2009;45:37–45.

    Article  Google Scholar 

  26. • Markert ML, Devlin BH, Mccarthy EA. Thymus transplantation. Clin Immunol. 2010;135:236–46. An update on treatment for the immune defects associated with 22qDS from the single US center performing thymus transplants for this condition.

    Article  CAS  Google Scholar 

  27. Markert ML, Devlin BH, Chinn I, Elizabeth A. Thymus transplantation in complete DiGeorge anomaly. 2009;44:61–70.

  28. Markert ML, Devlin BH, Alexieff MJ, Li J, McCarthy EA, Gupton SE. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood. 2007;109:4539–47.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sulagna C. Saitta.

Ethics declarations

Conflict of Interest

The authors declare no conflicts of interest relevant to this manuscript.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

This article is part of the Topical Collection on Immune Deficiency and Dysregulation

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kuo, C.Y., Signer, R. & Saitta, S.C. Immune and Genetic Features of the Chromosome 22q11.2 Deletion (DiGeorge Syndrome). Curr Allergy Asthma Rep 18, 75 (2018). https://doi.org/10.1007/s11882-018-0823-5

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11882-018-0823-5

Keywords

Navigation