Published Date: August 11, 2019

Full Text Article

Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis

Authors: M Fernanda Rozas, Felipe Benavides, Luis León, Gabriela M Repetto

Orphanet J Rare Dis. 2019 Aug 9;14(1):195. doi: 10.1186/s13023-019-1170-x.


BACKGROUND: Chromosome 22q11.2 microdeletion syndrome, a disorder caused by heterozygous loss of genetic material in chromosome region 22q11.2, has a broad range of clinical symptoms. The most common congenital anomalies involve the palate in 80% of patients, and the heart in 50-60% of them. The cause of the phenotypic variability is unknown. Patients usually harbor one of three common deletions sizes: 3, 2 and 1.5 Mb, between low copy repeats (LCR) designated A-D, A-C and A-B, respectively. This study aimed to analyze the association between these 3 deletion sizes and the presence of congenital cardiac and/or palatal malformations in individuals with this condition. A systematic review and meta-analysis were conducted, merging relevant published studies with data from Chilean patients to increase statistical power.

RESULTS: Eight articles out of 432 were included; the data from these studies was merged with our own, achieving a total of 1514 and 487 patients to evaluate cardiac and palate malformations, respectively. None of the compared deleted chromosomal segments were statistically associated with cardiac defects (ORAB v/s AC-AD: 0.654 [0.408-1.046]; OR AD v/s AB-AC: 1.291 [0.860-1.939]) or palate anomalies (ORAB v/s AC-AD: 1.731 [0.708-4.234]; OR AD v/s AB-AC: 0.628 [0.286-1.382]).

CONCLUSIONS: The lack of association between deletion size and CHD or PA found in this meta-analysis suggests that deletion size does not explain the incomplete penetrance of these 2 major manifestations, and that the critical region for the development of heart and palatal abnormalities is within LCR A-B, the smallest region of overlap among the three deletion sizes.

PMID: 31399107DOI: 10.1186/s13023-019-1170-xPMC: PMC6688301