22q11.2 duplication syndrome
22q11.2 duplication syndrome is a rare genetic disorder caused by a duplication of a segment at the end of chromosome 22.
| 22q11.2 duplication syndrome | |
|---|---|
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| Specialty | Medical genetics  |
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.
Diagnosis
References
- Wentzel C, Fernström M, Ohrner Y, Annerén G, Thuresson AC (2008). "Clinical variability of the 22q11.2 duplication syndrome". Eur J Med Genet. 51 (6): 501–10. doi:10.1016/j.ejmg.2008.07.005. PMID 18707033.
- Ou Z, Berg JS, Yonath H, et al. (April 2008). "Microduplications of 22q11.2 are frequently inherited and are associated with variable phenotypes". Genet. Med. 10 (4): 267–77. doi:10.1097/GIM.0b013e31816b64c2. PMID 18414210.
Further reading
- Ensenauer RE, Adeyinka A, Flynn HC, et al. (November 2003). "Microduplication 22q11.2, an emerging syndrome: clinical, cytogenetic, and molecular analysis of thirteen patients". Am. J. Hum. Genet. 73 (5): 1027–40. doi:10.1086/378818. PMC 1180483. PMID 14526392.
- Yobb TM, Somerville MJ, Willatt L, et al. (May 2005). "Microduplication and triplication of 22q11.2: a highly variable syndrome". Am. J. Hum. Genet. 76 (5): 865–76. doi:10.1086/429841. PMC 1199375. PMID 15800846.
- Portnoï MF, Lebas F, Gruchy N, et al. (August 2005). "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. doi:10.1002/ajmg.a.30847. PMID 16007629. S2CID 26654463.
- Alberti A, Romano C, Falco M, et al. (February 2007). "1.5 Mb de novo 22q11.21 microduplication in a patient with cognitive deficits and dysmorphic facial features". Clin. Genet. 71 (2): 177–82. doi:10.1111/j.1399-0004.2007.00750.x. PMID 17250668. S2CID 38867613.
- Zweier C, Sticht H, Aydin-Yaylagül I, Campbell CE, Rauch A (March 2007). "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. doi:10.1086/511993. PMC 1821102. PMID 17273972.