Genetics of Chromosome 22q11.2 Deletion Syndrome


The 22q11.2 deletion syndrome is the most frequent deletion syndrome in humans. The genomic architecture of this chromosomal region makes it prone to anomalous meiotic rearrangements causing the loss of genetic material in the parental gamete. Gene dosage‐dependent embryonic developmental processes are subsequently disrupted and lead to multiple birth malformations, the severity of which is modulated by other unknown genetic and environmental factors. The resulting clinical picture is a heterogeneous phenotype with no correlation with the genetic lesion. Currently, genetic diagnosis is mostly performed by gene dosage quantification techniques targeting region 22q11.2, but the recent development of whole‐genome scanning methods enabling a full molecular characterisation of patients under uniform criteria and a better genotype–phenotype correlation will help to understand the pathogenesis of this disorder.

Key Concepts:

  • The 22q11.2 deletion syndrome is the most common human microdeletion syndrome.

  • It usually occurs de novo, although an estimated 10% of cases are inherited.

  • LCR22s are homologous DNA sequences that spontaneously mediate the deletion process during meiosis.

  • Parents should be studied both genomically and cytogenetically to rule out carrier status or occasional balanced rearrangements.

  • Phenotypic variability is likely to be due to genetic and environmental factors during development, and it hampers a genotype–phenotype correlation.

  • Genomic techniques will contribute to a better genotypic characterisation and understanding of the disease.

Keywords: 22q11.2 deletion syndrome; DiGeorge syndrome; velocardiofacial syndrome; microdeletion syndrome; chromosome 22

Figure 1.

Schematic representation of chromosomal region 22q11.2. (a) Relative location of genes mentioned in the text; LCR22s and some examples of typical and atypical deletions. (b) Coverage of the region with FISH and MLPA probes and aCGH probes used for genetic diagnosis. Adapted from Database of Genomic Variants ( (Iafrate et al., ).

Figure 2.

Interchromosomal misalignment of LCR22s during meiotic recombination mediates deletion and duplication events in parental gametes.



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Further Reading

Baker K and Vorstman JA (2012) Is there a core neuropsychiatric phenotype in 22q11.2 deletion syndrome? Current Opinion in Neurology 25(2): 131–137.

Bassett AS, McDonald‐McGinn DM, Devriendt K et al. (2011) Practical guidelines for managing patients with 22q11.2 deletion syndrome. Journal of Pediatrics 159(2): 332–339.

Kobrynski LJ and Sullivan KE (2007) Velocardiofacial syndrome, DiGeorge syndrome: the chromosome 22q11.2 deletion syndromes. Lancet 370(9596): 1443–1452.

Philip N and Bassett A (2011) Cognitive, behavioural and psychiatric phenotype in 22q11.2 deletion syndrome. Behavior Genetics 41(3): 403–412.

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Fernández, Luis(Jan 2013) Genetics of Chromosome 22q11.2 Deletion Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0023881]