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DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis

Christine M Seroogy, MD
Section Editor
Jennifer M Puck, MD
Deputy Editor
Elizabeth TePas, MD, MS


DiGeorge syndrome (DGS) is a constellation of signs and symptoms associated with defective development of the pharyngeal pouch system. Most cases are caused by a heterozygous chromosomal deletion at 22q11.2. Chromosome 22q11.2 deletion syndrome (22qDS) includes DGS and other similar syndromes, such as velocardiofacial syndrome. The classic triad of features of DGS on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia (resulting from parathyroid hypoplasia).

Thymic hypoplasia in DGS results in a range of T cell deficits. Most patients with DGS have mild defects in T cell numbers and are not clinically immunodeficient. Approximately 1 percent, however, have a complete absence of thymic tissue and profound immunodeficiency. This form of DGS, called complete DGS, is a type of severe combined immunodeficiency (SCID) and is life threatening if not corrected with immune reconstitution by thymic or hematopoietic cell transplantation. (See "Hematopoietic cell transplantation for primary immunodeficiency".)

This topic reviews the clinical features and diagnosis of DGS. The epidemiology, pathogenesis, management, and prognosis of patients with DGS are presented separately. (See "DiGeorge (22q11.2 deletion) syndrome: Epidemiology and pathogenesis" and "DiGeorge (22q11.2 deletion) syndrome: Management and prognosis".)


The classic triad of features of DGS on presentation is conotruncal cardiac anomalies, hypoplastic thymus, and hypocalcemia [1]. However, the phenotype is quite variable (table 1), and there may be marked differences between affected individuals, even within a single family [2-7]. A broad spectrum characterizes the presence and severity of individual features, and the severity of each feature appears to be independent of other features. Older children with DGS may be detected through clinics for congenital heart defects or craniofacial clinics, may be referred to developmental specialists for poor school performance, or may be diagnosed due to frequent infections or autoimmune conditions.

Cardiac anomalies — Conotruncal cardiac defects occur in approximately 80 percent of DGS patients and, when present, are typically the initial abnormalities noted [2,3,5]. The term "conotruncal" refers to the distal portion of the fetal heart (trunco-aortic sac) at an early stage in development. The aortic and pulmonary roots subsequently develop from this area, and defects in these structures are referred to as conotruncal defects.

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Literature review current through: Oct 2017. | This topic last updated: Jul 25, 2017.
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  1. Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr 2011; 159:332.
  2. McDonald-McGinn DM, Sullivan KE. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore) 2011; 90:1.
  3. Ryan AK, Goodship JA, Wilson DI, et al. Spectrum of clinical features associated with interstitial chromosome 22q11 deletions: a European collaborative study. J Med Genet 1997; 34:798.
  4. Vantrappen G, Devriendt K, Swillen A, et al. Presenting symptoms and clinical features in 130 patients with the velo-cardio-facial syndrome. The Leuven experience. Genet Couns 1999; 10:3.
  5. McDonald-McGinn DM, Kirschner R, Goldmuntz E, et al. The Philadelphia story: the 22q11.2 deletion: report on 250 patients. Genet Couns 1999; 10:11.
  6. Motzkin B, Marion R, Goldberg R, et al. Variable phenotypes in velocardiofacial syndrome with chromosomal deletion. J Pediatr 1993; 123:406.
  7. Cirillo E, Giardino G, Gallo V, et al. Intergenerational and intrafamilial phenotypic variability in 22q11.2 deletion syndrome subjects. BMC Med Genet 2014; 15:1.
  8. McDonald-McGinn DM, LaRossa D, Goldmuntz E, et al. The 22q11.2 deletion: screening, diagnostic workup, and outcome of results; report on 181 patients. Genet Test 1997; 1:99.
  9. Goldmuntz E, Driscoll DA, Emanuel BS, et al. Evaluation of potential modifiers of the cardiac phenotype in the 22q11.2 deletion syndrome. Birth Defects Res A Clin Mol Teratol 2009; 85:125.
  10. Hiéronimus S, Bec-Roche M, Pedeutour F, et al. The spectrum of parathyroid gland dysfunction associated with the microdeletion 22q11. Eur J Endocrinol 2006; 155:47.
  11. Kar PS, Ogoe B, Poole R, Meeking D. Di-George syndrome presenting with hypocalcaemia in adulthood: two case reports and a review. J Clin Pathol 2005; 58:655.
  12. Harris JM, Hazenberg MD, Poulin JF, et al. Multiparameter evaluation of human thymic function: interpretations and caveats. Clin Immunol 2005; 115:138.
  13. Kolte L, Dreves AM, Ersbøll AK, et al. Association between larger thymic size and higher thymic output in human immunodeficiency virus-infected patients receiving highly active antiretroviral therapy. J Infect Dis 2002; 185:1578.
  14. Markert ML, Devlin BH, Alexieff MJ, et al. Review of 54 patients with complete DiGeorge anomaly enrolled in protocols for thymus transplantation: outcome of 44 consecutive transplants. Blood 2007; 109:4539.
  15. Kwan A, Abraham RS, Currier R, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA 2014; 312:729.
  16. Kwan A, Puck JM. History and current status of newborn screening for severe combined immunodeficiency. Semin Perinatol 2015; 39:194.
  17. http://primaryimmune.org/idf-advocacy-center/idf-scid-newborn-screening-campaign/ (Accessed on February 20, 2017).
  18. Markert ML, Alexieff MJ, Li J, et al. Postnatal thymus transplantation with immunosuppression as treatment for DiGeorge syndrome. Blood 2004; 104:2574.
  19. Ozcan E, Notarangelo LD, Geha RS. Primary immune deficiencies with aberrant IgE production. J Allergy Clin Immunol 2008; 122:1054.
  20. Markert ML, Alexieff MJ, Li J, et al. Complete DiGeorge syndrome: development of rash, lymphadenopathy, and oligoclonal T cells in 5 cases. J Allergy Clin Immunol 2004; 113:734.
  21. Vu QV, Wada T, Toma T, et al. Clinical and immunophenotypic features of atypical complete DiGeorge syndrome. Pediatr Int 2013; 55:2.
  22. Selim MA, Markert ML, Burchette JL, et al. The cutaneous manifestations of atypical complete DiGeorge syndrome: a histopathologic and immunohistochemical study. J Cutan Pathol 2008; 35:380.
  23. Piliero LM, Sanford AN, McDonald-McGinn DM, et al. T-cell homeostasis in humans with thymic hypoplasia due to chromosome 22q11.2 deletion syndrome. Blood 2004; 103:1020.
  24. Finocchi A, Di Cesare S, Romiti ML, et al. Humoral immune responses and CD27+ B cells in children with DiGeorge syndrome (22q11.2 deletion syndrome). Pediatr Allergy Immunol 2006; 17:382.
  25. 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; 86:141.
  26. Gennery AR. Immunological aspects of 22q11.2 deletion syndrome. Cell Mol Life Sci 2012; 69:17.
  27. Gennery AR, Barge D, O'Sullivan JJ, et al. Antibody deficiency and autoimmunity in 22q11.2 deletion syndrome. Arch Dis Child 2002; 86:422.
  28. Smith CA, Driscoll DA, Emanuel BS, et al. Increased prevalence of immunoglobulin A deficiency in patients with the chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Diagn Lab Immunol 1998; 5:415.
  29. Jawad AF, McDonald-Mcginn DM, Zackai E, Sullivan KE. Immunologic features of chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). J Pediatr 2001; 139:715.
  30. Schubert MS, Moss RB. Selective polysaccharide antibody deficiency in familial DiGeorge syndrome. Ann Allergy 1992; 69:231.
  31. Segni M, Zimmerman D. Autoimmune hyperthyroidism in two adolescents with DiGeorge/velocardiofacial syndrome (22q11 deletion). Eur J Pediatr 2002; 161:233.
  32. Kratz CP, Niehues T, Lyding S, et al. Evans syndrome in a patient with chromosome 22q11.2 deletion syndrome: a case report. Pediatr Hematol Oncol 2003; 20:167.
  33. Bruno B, Barbier C, Lambilliotte A, et al. Auto-immune pancytopenia in a child with DiGeorge syndrome. Eur J Pediatr 2002; 161:390.
  34. Tison BE, Nicholas SK, Abramson SL, et al. Autoimmunity in a cohort of 130 pediatric patients with partial DiGeorge syndrome. J Allergy Clin Immunol 2011; 128:1115.
  35. Choi JH, Shin YL, Kim GH, et al. Endocrine manifestations of chromosome 22q11.2 microdeletion syndrome. Horm Res 2005; 63:294.
  36. Davies K, Stiehm ER, Woo P, Murray KJ. Juvenile idiopathic polyarticular arthritis and IgA deficiency in the 22q11 deletion syndrome. J Rheumatol 2001; 28:2326.
  37. Cancrini C, Puliafito P, Digilio MC, et al. Clinical features and follow-up in patients with 22q11.2 deletion syndrome. J Pediatr 2014; 164:1475.
  38. Giardino G, Cirillo E, Maio F, et al. Gastrointestinal involvement in patients affected with 22q11.2 deletion syndrome. Scand J Gastroenterol 2014; 49:274.
  39. Chinen J, Rosenblatt HM, Smith EO, et al. Long-term assessment of T-cell populations in DiGeorge syndrome. J Allergy Clin Immunol 2003; 111:573.
  40. Zemble R, Luning Prak E, McDonald K, et al. Secondary immunologic consequences in chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Clin Immunol 2010; 136:409.
  41. 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; 164:882.
  42. Klocperk A, Grecová J, Šišmová K, et al. Helios expression in T-regulatory cells in patients with di George Syndrome. J Clin Immunol 2014; 34:864.
  43. McLean-Tooke A, Barge D, Spickett GP, Gennery AR. Immunologic defects in 22q11.2 deletion syndrome. J Allergy Clin Immunol 2008; 122:362.
  44. Davies JK, Telfer P, Cavenagh JD, et al. Autoimmune cytopenias in the 22q11.2 deletion syndrome. Clin Lab Haematol 2003; 25:195.
  45. DePiero AD, Lourie EM, Berman BW, et al. Recurrent immune cytopenias in two patients with DiGeorge/velocardiofacial syndrome. J Pediatr 1997; 131:484.
  46. Staple L, Andrews T, McDonald-McGinn D, et al. Allergies in patients with chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome) and patients with chronic granulomatous disease. Pediatr Allergy Immunol 2005; 16:226.
  47. Yagi H, Furutani Y, Hamada H, et al. Role of TBX1 in human del22q11.2 syndrome. Lancet 2003; 362:1366.
  48. Emanuel BS, McDonald-McGinn D, Saitta SC, Zackai EH. The 22q11.2 deletion syndrome. Adv Pediatr 2001; 48:39.
  49. Leopold C, De Barros A, Cellier C, et al. Laryngeal abnormalities are frequent in the 22q11 deletion syndrome. Int J Pediatr Otorhinolaryngol 2012; 76:36.
  50. Widdershoven JC, Spruijt NE, Spliet WG, et al. Histology of the pharyngeal constrictor muscle in 22q11.2 deletion syndrome and non-syndromic children with velopharyngeal insufficiency. PLoS One 2011; 6:e21672.
  51. Swillen A, Devriendt K, Legius E, et al. Intelligence and psychosocial adjustment in velocardiofacial syndrome: a study of 37 children and adolescents with VCFS. J Med Genet 1997; 34:453.
  52. Gerdes M, Solot C, Wang PP, et al. Cognitive and behavior profile of preschool children with chromosome 22q11.2 deletion. Am J Med Genet 1999; 85:127.
  53. Moss EM, Batshaw ML, Solot CB, et al. Psychoeducational profile of the 22q11.2 microdeletion: A complex pattern. J Pediatr 1999; 134:193.
  54. Wang PP, Woodin MF, Kreps-Falk R, Moss EM. Research on behavioral phenotypes: velocardiofacial syndrome (deletion 22q11.2). Dev Med Child Neurol 2000; 42:422.
  55. Van Aken K, De Smedt B, Van Roie A, et al. Motor development in school-aged children with 22q11 deletion (velocardiofacial/DiGeorge syndrome). Dev Med Child Neurol 2007; 49:210.
  56. Vorstman JA, Breetvelt EJ, Duijff SN, et al. Cognitive decline preceding the onset of psychosis in patients with 22q11.2 deletion syndrome. JAMA Psychiatry 2015; 72:377.
  57. Devriendt K, Swillen A, Fryns JP, et al. Renal and urological tract malformations caused by a 22q11 deletion. J Med Genet 1996; 33:349.
  58. Bassett AS, Chow EW, Husted J, et al. Clinical features of 78 adults with 22q11 Deletion Syndrome. Am J Med Genet A 2005; 138:307.
  59. Cohen E, Chow EW, Weksberg R, Bassett AS. Phenotype of adults with the 22q11 deletion syndrome: A review. Am J Med Genet 1999; 86:359.
  60. Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol 1999; 93:190.
  61. Cleveland WW. Immunologic reconstitution in the DiGeorge syndrome by fetal thymic transplant. Birth Defects Orig Artic Ser 1975; 11:352.
  62. Markert ML, Boeck A, Hale LP, et al. Transplantation of thymus tissue in complete DiGeorge syndrome. N Engl J Med 1999; 341:1180.
  63. Lingman Framme J, Borte S, von Döbeln U, et al. Retrospective analysis of TREC based newborn screening results and clinical phenotypes in infants with the 22q11 deletion syndrome. J Clin Immunol 2014; 34:514.
  64. Pretto D, Maar D, Yrigollen CM, et al. Screening newborn blood spots for 22q11.2 deletion syndrome using multiplex droplet digital PCR. Clin Chem 2015; 61:182.
  65. Knutsen AP, Baker MW, Markert ML. Interpreting low T-cell receptor excision circles in newborns with DiGeorge anomaly: importance of assessing naive T-cell markers. J Allergy Clin Immunol 2011; 128:1375.
  66. Vogels A, Schevenels S, Cayenberghs R, et al. Presenting symptoms in adults with the 22q11 deletion syndrome. Eur J Med Genet 2014; 57:157.
  67. Liu AP, Chow PC, Lee PP, et al. Under-recognition of 22q11.2 deletion in adult Chinese patients with conotruncal anomalies: implications in transitional care. Eur J Med Genet 2014; 57:306.
  68. Jalali GR, Vorstman JA, Errami A, et al. Detailed analysis of 22q11.2 with a high density MLPA probe set. Hum Mutat 2008; 29:433.
  69. Greenberg F. DiGeorge syndrome: an historical review of clinical and cytogenetic features. J Med Genet 1993; 30:803.
  70. Devriendt K, Swillen A, Fryns JP. Deletion in chromosome region 22q11 in a child with CHARGE association. Clin Genet 1998; 53:408.
  71. Online Medelian Inheritance in Man (OMIM) database. www.ncbi.nlm.nih.gov (Accessed on March 29, 2007).
  72. Sanlaville D, Verloes A. CHARGE syndrome: an update. Eur J Hum Genet 2007; 15:389.
  73. Sanka M, Tangsinmankong N, Loscalzo M, et al. Complete DiGeorge syndrome associated with CHD7 mutation. J Allergy Clin Immunol 2007; 120:952.
  74. Inoue H, Takada H, Kusuda T, et al. Successful cord blood transplantation for a CHARGE syndrome with CHD7 mutation showing DiGeorge sequence including hypoparathyroidism. Eur J Pediatr 2010; 169:839.
  75. Gennery AR, Slatter MA, Rice J, et al. Mutations in CHD7 in patients with CHARGE syndrome cause T-B + natural killer cell + severe combined immune deficiency and may cause Omenn-like syndrome. Clin Exp Immunol 2008; 153:75.
  76. Jyonouchi S, McDonald-McGinn DM, Bale S, et al. 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:e871.
  77. Quaderi NA, Schweiger S, Gaudenz K, et al. Opitz G/BBB syndrome, a defect of midline development, is due to mutations in a new RING finger gene on Xp22. Nat Genet 1997; 17:285.
  78. McDonald-McGinn DM, Driscoll DA, Bason L, et al. Autosomal dominant "Opitz" GBBB syndrome due to a 22q11.2 deletion. Am J Med Genet 1995; 59:103.
  79. Erickson RP, Díaz de Ståhl T, Bruder CE, Dumanski JP. A patient with 22q11.2 deletion and Opitz syndrome-like phenotype has the same deletion as velocardiofacial patients. Am J Med Genet A 2007; 143A:3302.
  80. Ammann AJ, Wara DW, Cowan MJ, et al. The DiGeorge syndrome and the fetal alcohol syndrome. Am J Dis Child 1982; 136:906.