Evaluating Genetic Disorders in the Neonate: The Role of Exome Sequencing in the NICU

Abstract

With recent advances in the technologies used for genetic diagnosis as well as our understanding of the genetic basis of disease, a growing list of options is available for providers when caring for a newborn with features suggesting an underlying genetic etiology. The choice of the most appropriate genetic test for a specific situation includes clinical considerations such as the phenotypic features and type of genetic abnormality suspected, as well as practical considerations such as cost and turnaround time. In this review, we discuss clinical exome sequencing in the context of genetic evaluation of newborns, including technical considerations, variant interpretation, and incidental/secondary findings. Strengths and limitations of exome sequencing are discussed and compared with those of other commonly known tests such as karyotype analysis, fluorescence in situ hybridization, chromosomal microarray, and sequencing panels, along with integration of results from prenatal testing if available. We also review future directions including genome sequencing and other emerging technologies that are starting to be used in clinical settings.