Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis
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(2019) 14:195
RESEARCH
Open Access
Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and metaanalysis M. Fernanda Rozas1, Felipe Benavides2,4, Luis León2,3 and Gabriela M. Repetto2*
Abstract 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. Keywords: Congenital heart defects, Chromosome 22q11.2 deletion syndrome, DiGeorge syndrome, Meta-analysis, Palate anomalies, Systematic review, Velocardiofacial syndrome
Background Chromosome 22q11.2 deletion syndrome (22q11.2DS) (MeSH Term “DiGeorge Syndrome”; MIM #188400, #192430) is a complex disorder that includes multiple congenital and neurodevelopmental anomalies. As the name implies, it is caused by a deletion in chromosome region 22q11.2. The syndrome presents phenotypic variability, which at first led it to be misidentified as * Correspondence: [email protected] 2 Centro de Genética y Genómica, Facultad de Medicina, Clínica Alemana Universidad del Desarrollo, Avda Las Condes, 12438 Santiago, Chile Full list of author information is available at the end of the article
several different pathological entities such as DiGeorge, conotruncal anomaly face, and velocardiofacial syndromes [1]. The most common manifestations are palate anomalies (PA), congenital heart defects (CHD), distinctive craniofacial features, learning difficulties, cognitive deficits and psychiatric morbidity [1]. Among rare disorders, 22q11.2DS is rel
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