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22q11.2 deletion syndrome

MIM.188400 22q11.2

Friday 3 October 2003

Definition: DiGeorge syndrome is mainly caused by a multigene, heterozygous, interstitial chromosomal deletion. Of the approximately 30 deleted genes, Tbx1 is the only gene that, after an extensive functional analysis in the mouse, has been found to be haploinsufficient.

The mutant phenotype is convincingly similar to the human syndrome, and its human homolog, TBX1, is the only gene for which mutations have been found in some patients without the chromosomal deletion. Tbx1 is an excellent tool to probe the genetic network governing embryonic pharyngeal development.

This syndrome is the most typical developmental defect of the embryonic pharyngeal system: a transient, vertebrate-specific structure that contributes to diverse tissues of the head, neck and thorax. Many birth defects, including a large fraction of congenital heart disease cases, derive from developmental problems of the pharyngeal system.

Del22q11.2 is an interstitial deletion of chromosome 22 associated with a characteristic phenotype clinically recognizable as DiGeorge syndrome, velocardiofacial syndrome or conotruncal anomaly face, which are collectively referred to as 22q11.2 deletion syndromes (22q11.2DS).

There are actually several versions of this deletion and the most common version eliminates 3 Mb of genomic DNA, including approximately 30 genes; smaller deletions are associated with essentially identical phenotypes.

It is still, therefore, uncertain whether 22q11.2DS is a contiguous gene deletion syndrome (i.e. a syndrome in which the deletion of different genes contributes to different aspects of the phenotype).

Del22q11 is the multigene deletion most commonly associated with phenotypic abnormalities (1:4000 live births) and it is an important cause of birth defects, including congenital heart disease and learning and psychiatric disorders.


- craniofacial anomalies

- thymic aplasia (thymic agenesis)
- parathyroid anomales

  • parathyroid hypoplasia
  • parathyroid agenesis (aparathyroid aplasia)

- accessory thyroid tissue

- cardiovascular anomalies

- vascular anomalies

- digestive

- spina bifida (20430655)

- abnormal growth of the thyroid cartilage (3822935)
- laryngeal atresia
- upper limb malformations


- hepatoblastoma (14692228)
- renal-cell carcinoma (14692228)
- Wilms tumor (21456030)


- contiguous gene syndrome involving deletion of the DiGeorge syndrome chromosome region (DGCR) involving mutations in TUP-like enhancer of split 1 (TUPLE1) (MIM.600237) and DiGeorge critical region gene 2 (DGCR2) (MIM.600594)
- deletion of the 22q11.2 region
- germline mutation in the TBX1 gene (MIM.602054)


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Trends Genet. 2001 Oct;17(10):S13-7. PMID: 11585671

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