22q11.2 duplication syndrome explained

22q11.2 duplication syndrome is a rare genetic disorder caused by a duplication of a segment at the end of chromosome 22.

Presentation

The most frequent reported symptoms in patients with 22q11.2 duplication syndrome are intellectual disability/learning disability (97% of patients), delayed psychomotor development (67% of patients), growth retardation (63% of patients) and muscular hypotonia (43% of patients).^[1] However, these are common and relatively non-specific indications for cytogenetic analysis, and the extent to which the duplication of 22q11.2 causes these features is currently unknown. The duplication is frequently inherited from a normal parent, so it is clear that intellectual development can be normal.

Genetics

Duplications of 22q11 vary in size and thereby in gene content. They include the typical common 3-Mb microduplication, 1.5-Mb nested duplication, consistent with non-allelic homologous recombination (NAHR) using distinct low-copy repeats. These microduplications likely represent the predicted reciprocal rearrangements to the microdeletions characterized in the 22q11.2 region.^[2] Smaller microduplications may occur within this highly dynamic with frequent rearrangements using alternative low-copy repeats as recombination substrates within and distal to the DiGeorge syndrome region.

Origin of duplication

The majority of 22q11 duplications are inherited often from a parent with a normal or near-normal phenotype. This is in sharp distinction to 22q11 deletion syndrome where about 90% of cases are caused by mutations that occur de novo.

Further reading

• Ensenauer RE, Adeyinka A, Flynn HC . Microduplication 22q11.2, an emerging syndrome: clinical, cytogenetic, and molecular analysis of thirteen patients . Am. J. Hum. Genet. . 73 . 5 . 1027–40 . November 2003 . 14526392 . 1180483 . 10.1086/378818 . etal.
• Yobb TM, Somerville MJ, Willatt L . Microduplication and triplication of 22q11.2: a highly variable syndrome . Am. J. Hum. Genet. . 76 . 5 . 865–76 . May 2005 . 15800846 . 1199375 . 10.1086/429841 . etal.
• Portnoï MF, Lebas F, Gruchy N . 22q11.2 duplication syndrome: two new familial cases with some overlapping features with DiGeorge/velocardiofacial syndromes . Am. J. Med. Genet. A . 137 . 1 . 47–51 . August 2005 . 16007629 . 10.1002/ajmg.a.30847 . 26654463 . etal.
• Alberti A, Romano C, Falco M . 1.5 Mb de novo 22q11.21 microduplication in a patient with cognitive deficits and dysmorphic facial features . Clin. Genet. . 71 . 2 . 177–82 . February 2007 . 17250668 . 10.1111/j.1399-0004.2007.00750.x . 38867613 . etal.
• Zweier C, Sticht H, Aydin-Yaylagül I, Campbell CE, Rauch A . Human TBX1 missense mutations cause gain of function resulting in the same phenotype as 22q11.2 deletions . Am. J. Hum. Genet. . 80 . 3 . 510–7 . March 2007 . 17273972 . 1821102 . 10.1086/511993 .

External links

• Genetics Home Reference

Notes and References

1. Wentzel C, Fernström M, Ohrner Y, Annerén G, Thuresson AC . Clinical variability of the 22q11.2 duplication syndrome . Eur J Med Genet . 51 . 6 . 501–10 . 2008 . 18707033 . 10.1016/j.ejmg.2008.07.005 .
2. Ou Z, Berg JS, Yonath H . Microduplications of 22q11.2 are frequently inherited and are associated with variable phenotypes . Genet. Med. . 10 . 4 . 267–77 . April 2008 . 18414210 . 10.1097/GIM.0b013e31816b64c2 . etal. free .