Role of copy number variants in structural birth defects

Human genomes include copy number variants (CNVs), defined as regions with DNA gains or losses. Pathologic CNVs, which are larger and often occur de novo, are increasingly associated with disease. Given advances in genetic testing, namely microarray-based comparative genomic hybridization and single nucleotide polymorphism arrays, previously unidentified genotypic aberrations can now be correlated with phenotypic anomalies. The objective of this study was to conduct a nonsystematic literature review to document the role of CNVs as they relate to isolated structural anomalies of the craniofacial, respiratory, renal, and cardiac systems.

All full-length articles in the PubMed database through May 2011 that discussed CNVs and isolated structural defects of the craniofacial, respiratory, renal, and cardiac systems were considered. Search terms queried include CNV, copy number variation, array comparative genomic hybridization, birth defects, craniofacial defects, respiratory defects, renal defects, and congenital heart disease. Reports published in languages other than English and articles regarding CNVs and neurocognitive deficits were not considered.

Evidence supports that putatively pathogenic CNVs occur at an increased frequency in patients with isolated structural birth defects and implicate specific regions of the genome. Through CNV detection, advances have been made in identifying genes and specific loci that underlie isolated birth defects.

Although limited studies have been published, the promising evidence reviewed here warrants the continued investigation of CNVs in children with isolated structural birth defects. Patient care and genetic counseling stand to improve through a better understanding of CNVs and their effect on disease phenotype.