digeorge syndrome


Summary: Congenital syndrome characterized by a wide spectrum of characteristics including the absence of the THYMUS and PARATHYROID GLANDS resulting in T-cell immunodeficiency, HYPOCALCEMIA, defects in the outflow tract of the heart, and craniofacial anomalies.

Top Publications

  1. McDonald McGinn D, Zackai E. Genetic counseling for the 22q11.2 deletion. Dev Disabil Res Rev. 2008;14:69-74 pubmed publisher
    ..With this in mind, a variety of prenatal monitoring techniques, as well as, preimplantation genetic diagnosis are available depending on the specific level of risk. ..
  2. Meechan D, Maynard T, Gopalakrishna D, Wu Y, LaMantia A. When half is not enough: gene expression and dosage in the 22q11 deletion syndrome. Gene Expr. 2007;13:299-310 pubmed
  3. Yu S, Graf W, Shprintzen R. Genomic disorders on chromosome 22. Curr Opin Pediatr. 2012;24:665-71 pubmed publisher
    ..2 deletion syndrome and DiGeorge syndrome. This review will focus on the recent literature dealing with both the molecular and clinical aspects of ..
  4. Patel K, Akhter J, Kobrynski L, Benjamin Gathmann M, Gathman B, Davis O, et al. Immunoglobulin deficiencies: the B-lymphocyte side of DiGeorge Syndrome. J Pediatr. 2012;161:950-3 pubmed publisher
    b>DiGeorge syndrome is associated with a T-lymphocyte immunodeficiency. The prevalence of hypogammaglobulinemia has not been reported...
  5. Prasad S, Howley S, Murphy K. Candidate genes and the behavioral phenotype in 22q11.2 deletion syndrome. Dev Disabil Res Rev. 2008;14:26-34 pubmed publisher
    ..The study of 22q11.2DS provides an attractive model to increase our understanding of the development and pathogenesis of schizophrenia and other psychiatric disorders in 22q11.2DS and in wider population. ..
  6. Shashi V, Kwapil T, Kaczorowski J, Berry M, Santos C, Howard T, et al. Evidence of gray matter reduction and dysfunction in chromosome 22q11.2 deletion syndrome. Psychiatry Res. 2010;181:1-8 pubmed publisher
    ..The correlation of these volumetric reductions with poor neurocognition indicates that these brain regions may mediate higher neurocognitive functions implicated in schizophrenia. ..
  7. Swaby J, Silversides C, Bekeschus S, Piran S, Oechslin E, Chow E, et al. Complex congenital heart disease in unaffected relatives of adults with 22q11.2 deletion syndrome. Am J Cardiol. 2011;107:466-71 pubmed publisher
    ..These findings have potential implications for the genetic counseling of families of those with 22q11DS and support the notion that interacting genetic variants might contribute to the variable expression of 22q11DS. ..
  8. Markert M, Devlin B, Chinn I, McCarthy E, Li Y. Factors affecting success of thymus transplantation for complete DiGeorge anomaly. Am J Transplant. 2008;8:1729-36 pubmed publisher
    ..Although subtle immune effects may yet be associated with some of the factors tested, it is remarkable that consistently good immune outcomes result despite variation in dose, HLA matching and use of immunosuppression. ..
  9. Momma K. Cardiovascular anomalies associated with chromosome 22q11.2 deletion syndrome. Am J Cardiol. 2010;105:1617-24 pubmed publisher
    ..2 deletion. In conclusion, conotruncal anomaly associated with aortic arch and ductus arteriosus anomalies should increase the suspicion of 22q11.2 deletion. ..

More Information


  1. Calderón J, Puga A, Guzmán M, Astete C, Arriaza M, Aracena M, et al. VEGFA polymorphisms and cardiovascular anomalies in 22q11 microdeletion syndrome: a case-control and family-based study. Biol Res. 2009;42:461-8 pubmed publisher
  2. Tomita Mitchell A, Mahnke D, Larson J, Ghanta S, Feng Y, Simpson P, et al. Multiplexed quantitative real-time PCR to detect 22q11.2 deletion in patients with congenital heart disease. Physiol Genomics. 2010;42A:52-60 pubmed publisher
    22q11.2 Deletion syndrome (22q11.2 DS) [DiGeorge syndrome type 1 (DGS1)] occurs in ?1:3,000 live births; 75% of children with DGS1 have severe congenital heart disease requiring early intervention...
  3. Kates W, Krauss B, AbdulSabur N, Colgan D, Antshel K, Higgins A, et al. The neural correlates of non-spatial working memory in velocardiofacial syndrome (22q11.2 deletion syndrome). Neuropsychologia. 2007;45:2863-73 pubmed
  4. Goldmuntz E, Driscoll D, Emanuel B, McDonald McGinn D, Mei M, Zackai E, et al. Evaluation of potential modifiers of the cardiac phenotype in the 22q11.2 deletion syndrome. Birth Defects Res A Clin Mol Teratol. 2009;85:125-9 pubmed publisher
    ..Variation in the cardiac phenotype observed between individuals with a 22q11.2 deletion does not appear to be related to sex, race, or five sequence variants in four folate-related genes that are located outside of the 22q11.2 region. ..
  5. Gothelf D, Schaer M, Eliez S. Genes, brain development and psychiatric phenotypes in velo-cardio-facial syndrome. Dev Disabil Res Rev. 2008;14:59-68 pubmed publisher
    ..The other genes and environmental factors that shape the unique neuropsychiatric phenotype of VCFS are yet to be discovered. ..
  6. Fernandez L, Lapunzina P, Pajares I, Palomares M, Martinez I, Fernández B, et al. Unrelated chromosomal anomalies found in patients with suspected 22q11.2 deletion. Am J Med Genet A. 2008;146A:1134-41 pubmed publisher
  7. Carlier M, Desplanches A, Philip N, Stefanini S, Vicari S, Volterra V, et al. Laterality preference and cognition: cross-syndrome comparison of patients with trisomy 21 (Down), del7q11.23 (Williams-Beuren) and del22q11.2 (DiGeorge or Velo-Cardio-Facial) syndromes. Behav Genet. 2011;41:413-22 pubmed publisher
  8. Hay B. Deletion 22q11: spectrum of associated disorders. Semin Pediatr Neurol. 2007;14:136-9 pubmed
    ..Recognition of the features associated with velocardiofacial syndrome allows for an inclusive diagnosis and more comprehensive care. ..
  9. Markert M, Li J, Devlin B, Hoehner J, Rice H, Skinner M, et al. Use of allograft biopsies to assess thymopoiesis after thymus transplantation. J Immunol. 2008;180:6354-64 pubmed
    ..In summary, combining biopsy and autopsy data, allogeneic thymus tissues showed thymopoiesis in 24 of 29 (86%) evaluable transplants. The results of these biopsies led to improved care of these complex patients. ..
  10. Shashi V, Howard T, Keshavan M, Kaczorowski J, Berry M, Schoch K, et al. COMT and anxiety and cognition in children with chromosome 22q11.2 deletion syndrome. Psychiatry Res. 2010;178:433-6 pubmed publisher
    ..The Val allele was associated with poor IQ, processing speed, executive function and a higher frequency of anxiety disorders, underscoring the importance of the COMT gene in the childhood psychopathology in 22q11DS. ..
  11. Shprintzen R. Velo-cardio-facial syndrome: 30 Years of study. Dev Disabil Res Rev. 2008;14:3-10 pubmed publisher
    ..Therefore, interest in understanding the nature of psychiatric illness in the syndrome remains strong. ..
  12. Coppinger J, McDonald McGinn D, Zackai E, Shane K, Atkin J, Asamoah A, et al. Identification of familial and de novo microduplications of 22q11.21-q11.23 distal to the 22q11.21 microdeletion syndrome region. Hum Mol Genet. 2009;18:1377-83 pubmed publisher
    ..The variable phenotypes and preponderance of familial cases obfuscate the clinical relevance of the molecular data and emphasize the need for careful parental assessments and clinical correlations. ..
  13. Voss A, Vanyai H, Collin C, Dixon M, McLennan T, Sheikh B, et al. MOZ regulates the Tbx1 locus, and Moz mutation partially phenocopies DiGeorge syndrome. Dev Cell. 2012;23:652-63 pubmed publisher
    b>DiGeorge syndrome, caused by a 22q11 microdeletion or mutation of the TBX1 gene, varies in severity greatly, even among monozygotic twins...
  14. Hercher L, Bruenner G. Living with a child at risk for psychotic illness: the experience of parents coping with 22q11 deletion syndrome: an exploratory study. Am J Med Genet A. 2008;146A:2355-60 pubmed publisher
  15. Jolin E, Weller R, Jessani N, Zackai E, McDonald McGinn D, Weller E. Affective disorders and other psychiatric diagnoses in children and adolescents with 22q11.2 Deletion Syndrome. J Affect Disord. 2009;119:177-80 pubmed publisher
    ..Early psychiatric screening and monitoring appears warranted in 22qDS patients. ..
  16. Green T, Gothelf D, Glaser B, Debbane M, Frisch A, Kotler M, et al. Psychiatric disorders and intellectual functioning throughout development in velocardiofacial (22q11.2 deletion) syndrome. J Am Acad Child Adolesc Psychiatry. 2009;48:1060-8 pubmed publisher
    ..Prospective longitudinal studies are needed to examine the nature of age-related cognitive changes and their association with psychiatric morbidity in VCFS. ..
  17. Johnston P, Donnelly D, Donnelly D, Morrison P, Hunter S. DiGeorge syndrome presenting as late onset hypocalcaemia in adulthood. Ulster Med J. 2008;77:201-2 pubmed
    ..neonatal hypocalcaemia and velopharyngeal incompetence during childhood, prompted chromosomal analysis for DiGeorge Syndrome. Fluorescence in situ hybridisation (FISH) analysis revealed a deletion of chromosome 22q11.2...
  18. Hooper S, Curtiss K, Schoch K, Keshavan M, Allen A, Shashi V. A longitudinal examination of the psychoeducational, neurocognitive, and psychiatric functioning in children with 22q11.2 deletion syndrome. Res Dev Disabil. 2013;34:1758-69 pubmed publisher
    ..These findings begin to elucidate the trajectory of changes in psychopathology in children with 22q11DS in the years leading up to the onset of major psychiatric illnesses. ..
  19. Meechan D, Tucker E, Maynard T, LaMantia A. Diminished dosage of 22q11 genes disrupts neurogenesis and cortical development in a mouse model of 22q11 deletion/DiGeorge syndrome. Proc Natl Acad Sci U S A. 2009;106:16434-45 pubmed publisher
    ..Such developmental disruption may alter cortical circuitry and establish vulnerability for developmental disorders, including schizophrenia and autism. ..
  20. Tan G, Arnone D, McIntosh A, Ebmeier K. Meta-analysis of magnetic resonance imaging studies in chromosome 22q11.2 deletion syndrome (velocardiofacial syndrome). Schizophr Res. 2009;115:173-81 pubmed publisher
    22q11.2 deletion syndrome (22q11.2DS), also known as velocardiofacial syndrome (VCFS) or DiGeorge Syndrome, is a genetic disorder due to a micro deletion on chromosome 22q11.2...
  21. Zhou J, Pashmforoush M, Sucov H. Endothelial neuropilin disruption in mice causes DiGeorge syndrome-like malformations via mechanisms distinct to those caused by loss of Tbx1. PLoS ONE. 2012;7:e32429 pubmed publisher
    The spectrum of human congenital malformations known as DiGeorge syndrome (DGS) is replicated in mice by mutation of Tbx1...
  22. de la Morena M, Eitson J, Dozmorov I, Belkaya S, Hoover A, Anguiano E, et al. Signature MicroRNA expression patterns identified in humans with 22q11.2 deletion/DiGeorge syndrome. Clin Immunol. 2013;147:11-22 pubmed publisher
    ..In summary, microRNA profiling of chromosome 22q11.2 deletion syndrome/DiGeorge patients revealed a signature microRNA expression pattern distinct from normal controls with clinical relevance. ..
  23. Van Den Berge K, Diderich K, Poddighe P, Berghout A. Symptomatic hypoparathyroidism based on a 22q11 deletion first diagnosed in a 43-year-old woman. Neth J Med. 2009;67:102-4 pubmed
    ..diagnosed with dysgenesis of the parathyroid glands due to a de novo microdeletion in chromosome 22q11 or DiGeorge syndrome. This syndrome is characterised by a considerable variability in clinical symptoms, including heart defects, ..
  24. Beaujard M, Chantot S, Dubois M, Keren B, Carpentier W, Mabboux P, et al. Atypical deletion of 22q11.2: detection using the FISH TBX1 probe and molecular characterization with high-density SNP arrays. Eur J Med Genet. 2009;52:321-7 pubmed publisher
    ..2. We conclude that FISH with the TBX1 probe is an accurate diagnostic tool for 22q11.2 DS, with a higher sensitivity than FISH using standard probes, detecting all but the rarest deletions, greatly reducing the false negative rate. ..
  25. Erickson R, Díaz de Ståhl T, Bruder C, Dumanski J. 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:3302-8 pubmed
    ..2 deletion. He shares the same deletion as patients with velocardiofacial and DiGeorge syndrome.
  26. Gothelf D, Penniman L, Gu E, Eliez S, Reiss A. Developmental trajectories of brain structure in adolescents with 22q11.2 deletion syndrome: a longitudinal study. Schizophr Res. 2007;96:72-81 pubmed
    ..2DS varies from that observed in healthy controls. Further longitudinal studies are likely to elucidate brain developmental trajectories in 22q11.2DS and their association to psychotic disorders and cognitive deficits in this population. ..
  27. Sundaram U, McDonald McGinn D, Huff D, Emanuel B, Zackai E, Driscoll D, et al. Primary amenorrhea and absent uterus in the 22q11.2 deletion syndrome. Am J Med Genet A. 2007;143A:2016-8 pubmed
    ..The diagnosis of 22q11.2 deletion may be considered in a female with Mullerian agenesis, particularly, in association with a history of learning difficulties and speech delay. ..
  28. Kiehl T, Chow E, Mikulis D, George S, Bassett A. Neuropathologic features in adults with 22q11.2 deletion syndrome. Cereb Cortex. 2009;19:153-64 pubmed publisher
    ..Both early developmental brain abnormalities and fetal and later microvascular pathology may play a role in the pathogenesis of the neuropsychiatric phenotype of 22qDS, including white matter abnormalities and schizophrenia. ..
  29. Dufour F, Schaer M, Debbane M, Farhoumand R, Glaser B, Eliez S. Cingulate gyral reductions are related to low executive functioning and psychotic symptoms in 22q 11.2 deletion syndrome. Neuropsychologia. 2008;46:2986-92 pubmed publisher
    ..The mechanisms by which these changes may modulate executive functioning and the expression of psychosis are discussed. ..
  30. Ryckebusch L, Bertrand N, Mesbah K, Bajolle F, Niederreither K, Kelly R, et al. Decreased levels of embryonic retinoic acid synthesis accelerate recovery from arterial growth delay in a mouse model of DiGeorge syndrome. Circ Res. 2010;106:686-94 pubmed publisher
    ..Our data suggest that differences in levels of embryonic RA may contribute to the variability in great artery anomalies observed in DGS/VCFS patients. ..
  31. Herman S, Guo T, McGinn D, Blonska A, Shanske A, Bassett A, et al. Overt cleft palate phenotype and TBX1 genotype correlations in velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients. Am J Med Genet A. 2012;158A:2781-7 pubmed publisher
    Velo-cardio-facial syndrome/DiGeorge syndrome, also known as 22q11.2 deletion syndrome (22q11DS) is the most common microdeletion syndrome, with an estimated incidence of 1/2,000-1/4,000 live births...
  32. Antshel K, Fremont W, Kates W. The neurocognitive phenotype in velo-cardio-facial syndrome: a developmental perspective. Dev Disabil Res Rev. 2008;14:43-51 pubmed publisher
    ..The most salient of these is the need for more longitudinal designs with carefully matched control participants. ..
  33. Carelle Calmels N, Saugier Veber P, Girard Lemaire F, Rudolf G, Doray B, Guerin E, et al. Genetic compensation in a human genomic disorder. N Engl J Med. 2009;360:1211-6 pubmed publisher
    ..through quantitative-expression analyses of genes located within the genetic region associated with the DiGeorge syndrome. This finding has implications for genetic counseling and represents a case of genetic compensation in a ..
  34. Zhang Z, Baldini A. In vivo response to high-resolution variation of Tbx1 mRNA dosage. Hum Mol Genet. 2008;17:150-7 pubmed
    ..Overall, our data suggest that there are developmental process-specific gene dosage thresholds beyond which the phenotype worsens very rapidly with very small mRNA level reductions. ..
  35. Busse T, Graham J, Feldman G, Perin J, Catherwood A, Knowlton R, et al. High-Resolution genomic arrays identify CNVs that phenocopy the chromosome 22q11.2 deletion syndrome. Hum Mutat. 2011;32:91-7 pubmed publisher
    ..In patients with phenotypes suggestive of the 22q11.2 syndrome spectrum and normal FISH, microarray analysis can uncover the molecular basis of other genomic disorders whose features overlap those of 22q11.2 deletions. ..
  36. Cao Z, Yu R, Dun K, Burke J, Caplin N, Greenaway T. 22q11.2 deletion presenting with severe hypocalcaemia, seizure and basal ganglia calcification in an adult man. Intern Med J. 2011;41:63-6 pubmed publisher
    ..2. The extraordinary feature of this case is the adult presentation of hypocalcaemia, hypoparathyroidism and basal ganglia calcification due to 22q11.2 deletion. ..
  37. Jalali G, Vorstman J, Errami A, Vijzelaar R, Biegel J, Shaikh T, et al. Detailed analysis of 22q11.2 with a high density MLPA probe set. Hum Mutat. 2008;29:433-40 pubmed
    ..In patients with the relevant phenotypic characteristics, this MLPA-HD probe set could replace FISH for the clinical diagnosis of 22q11.2 deletions and duplications. ..
  38. Sanka M, Tangsinmankong N, Loscalzo M, Sleasman J, Dorsey M. Complete DiGeorge syndrome associated with CHD7 mutation. J Allergy Clin Immunol. 2007;120:952-4 pubmed
  39. Tutulan Cunita A, Budisteanu M, Papuc S, Dupont J, Blancho D, Lebbar A, et al. Atypical presentations of 22q11.2 deletion syndrome: explaining the genetic defects and genome architecture. Psychiatry Res. 2012;197:356-7 pubmed publisher
    ..We present two atypical cases of 22q11.2 deletion syndrome and suggest a preferential occurrence of the breakpoints in regions poor in repetitive elements of SINE/Alu family. ..
  40. Babcock M, Yatsenko S, Hopkins J, Brenton M, Cao Q, de Jong P, et al. Hominoid lineage specific amplification of low-copy repeats on 22q11.2 (LCR22s) associated with velo-cardio-facial/digeorge syndrome. Hum Mol Genet. 2007;16:2560-71 pubmed
    ..In summary, our results are consistent with a lineage specific coupling between gene and LCR22 duplication events. The LCR22s thus serve as an important model for evolution of genome variation. ..
  41. Vallaster M, Vallaster C, Wu S. Epigenetic mechanisms in cardiac development and disease. Acta Biochim Biophys Sin (Shanghai). 2012;44:92-102 pubmed publisher
    ..Furthermore, we speculate that an epigenetic signature, comprised of TF occupancy, histone modifications, and overall chromatin organization, is an underlying mechanism that governs cardiac morphogenesis and disease. ..
  42. Théveniau Ruissy M, Dandonneau M, Mesbah K, Ghez O, Mattei M, Miquerol L, et al. The del22q11.2 candidate gene Tbx1 controls regional outflow tract identity and coronary artery patterning. Circ Res. 2008;103:142-8 pubmed publisher
    TBX1, encoding a T-box containing transcription factor, is the major candidate gene for del22q11.2 or DiGeorge syndrome, characterized by craniofacial and cardiovascular defects including tetralogy of Fallot and common arterial trunk...
  43. Evers L, de Die Smulders C, Smeets E, Clerkx M, Curfs L. The velo-cardio-facial syndrome: the spectrum of psychiatric problems and cognitive deterioration at adult age. Genet Couns. 2009;20:307-15 pubmed
    ..Aside from the described behavioral phenotype in literature, a moderate, severe or profound intellectual disability may be present. Special attention should be given to cognitive deterioration. ..
  44. Scambler P. 22q11 deletion syndrome: a role for TBX1 in pharyngeal and cardiovascular development. Pediatr Cardiol. 2010;31:378-90 pubmed publisher
    ..This article summarises the tissue specific and temporal requirements for Tbx1, and attempts to synthesis what is know about the developmental pathways under its control. ..
  45. Debbane M, Van der Linden M, Glaser B, Eliez S. Source monitoring for actions in adolescents with 22q11.2 deletion syndrome (22q11DS). Psychol Med. 2008;38:811-20 pubmed
    ..These deficits are discussed in terms of early cognitive processes associated with genetic risk for schizophrenia. ..
  46. Schaer M, Debbane M, Bach Cuadra M, Ottet M, Glaser B, Thiran J, et al. Deviant trajectories of cortical maturation in 22q11.2 deletion syndrome (22q11DS): a cross-sectional and longitudinal study. Schizophr Res. 2009;115:182-90 pubmed publisher
  47. Rope A, Cragun D, Saal H, Hopkin R. DiGeorge anomaly in the absence of chromosome 22q11.2 deletion. J Pediatr. 2009;155:560-5 pubmed publisher
    ..2 deletion, and attempts to resolve some confusing features of conditions associated with DGA. ..
  48. McDonald McGinn D, Sullivan K. Chromosome 22q11.2 deletion syndrome (DiGeorge syndrome/velocardiofacial syndrome). Medicine (Baltimore). 2011;90:1-18 pubmed publisher
    Chromosome 22q11.2 deletion syndrome is a common syndrome also known as DiGeorge syndrome and velocardiofacial syndrome...
  49. Ben Shachar S, Ou Z, Shaw C, Belmont J, Patel M, Hummel M, et al. 22q11.2 distal deletion: a recurrent genomic disorder distinct from DiGeorge syndrome and velocardiofacial syndrome. Am J Hum Genet. 2008;82:214-21 pubmed publisher
    Microdeletions within chromosome 22q11.2 cause a variable phenotype, including DiGeorge syndrome (DGS) and velocardiofacial syndrome (VCFS)...
  50. Vorstman J, Chow E, Ophoff R, van Engeland H, Beemer F, Kahn R, et al. Association of the PIK4CA schizophrenia-susceptibility gene in adults with the 22q11.2 deletion syndrome. Am J Med Genet B Neuropsychiatr Genet. 2009;150B:430-3 pubmed publisher
    ..Second, the results of this study indicate that variation at PIK4CA may be a relevant factor influencing the risk of schizophrenia in individuals with 22q11DS. ..
  51. Bittel D, Yu S, Newkirk H, Kibiryeva N, Holt A, Butler M, et al. Refining the 22q11.2 deletion breakpoints in DiGeorge syndrome by aCGH. Cytogenet Genome Res. 2009;124:113-20 pubmed publisher
    ..036 to 17.398 Mb. This region includes the genes DGCR6 (DiGeorge syndrome critical region protein 6) and PRODH (proline dehydrogenase 1), along with three open reading frames that ..
  52. Guo T, McDonald McGinn D, Blonska A, Shanske A, Bassett A, Chow E, et al. Genotype and cardiovascular phenotype correlations with TBX1 in 1,022 velo-cardio-facial/DiGeorge/22q11.2 deletion syndrome patients. Hum Mutat. 2011;32:1278-89 pubmed publisher
    ..This work demonstrates that common DNA variations in TBX1 do not explain variable cardiovascular expression in 22q11DS patients, implicating existence of modifiers in other genes on 22q11.2 or elsewhere in the genome. ..
  53. Aggarwal V, Morrow B. Genetic modifiers of the physical malformations in velo-cardio-facial syndrome/DiGeorge syndrome. Dev Disabil Res Rev. 2008;14:19-25 pubmed publisher
    Velo-cardio-facial syndrome/DiGeorge syndrome (VCFS/DGS), the most common micro-deletion disorder in humans, is characterized by craniofacial, parathyroid, and thymic defects as well as cardiac outflow tract malformations...