Chromosome Abnormalities in Neonates with Congenital Heart Defects

Congenital heart disease (CHD) contributes to the rate of birth defects in the population with an incidence of nearly 1% of all live births (1). CHD has significant Public Health importance due to its high incidence, clinical severity, and complexity of medical management. In some cases, efficiently diagnosing the underlying cause of CHD is essential to providing optimal clinical care. The etiology of CHD is hypothesized to be largely multifactorial in nature, but chromosome abnormalities account for 8-13% of all CHD (2, 3). It has recently been recognized that submicroscopic chromosome abnormalities known as copy number variants (CNVs) may also play a role in causing CHD. Array comparative genomic hybridization (array CGH) has recently been added as a first-tier test for neonates with CHD at our institution, due to its ability to detect CNVs which were previously undetectable by classical cytogenetic analysis. Our study is a prospective chart review of data from neonates with CHD admitted to the Cardiac Intensive Care Unit at Children’s Hospital of Pittsburgh of UPMC. The purpose of this study was to assess the clinical efficacy of array CGH as a first-tier test in this population. Our results show that array CGH increases the detection rate of chromosome aberrations by 20% above classical cytogenetic analysis alone. However, the majority of CNVs detected in our study had unclear clinical significance. For this reason, collaboration between Cardiology and Medical Genetics is essential to interpreting the clinical relevance of array CGH results in order to provide an accurate, timely genetic diagnosis and ultimately improve the clinical care of neonates with CHD