Utility and Challenges of Next Generation Sequencing in Pediatric Disorders

Several recently developed technologies, collectively known as next-generation sequencing (NGS), or massively parallel sequencing, are designed to gather data from large portions of the genome in a single experiment. Whole exome sequencing (WES) is a common implementation of NGS targeted to coding regions, or exons, where most disease causing mutations are believed to reside. As WES is becoming more cost effective, it is shifting from research to clinical applications, particularly for the diagnosis of rare genetic disorders of unknown etiology. NGS is also gaining ground in the specialized fields of pathology, prenatal diagnosis, and copy number detection. The large scope of NGS is raising important ethical and policy issues, such as reporting of incidental or secondary findings. In this review, these topics are discussed with specific focus on pediatrics, drawing examples from the study of intellectual disability and congenital heart disease.