Next generation sequencing in neonatology: what does it mean for the next generation?

Hum Genet. 2022 May;141(5):1027-1034. doi: 10.1007/s00439-022-02438-9. Epub 2022 Mar 29.


Rapid whole genome sequencing (WGS) and whole exome sequencing (WES), sometimes referred to as "next generation sequencing" (NGS) are now recommended by some experts as a first-line diagnostic test to diagnose infants with suspected monogenic conditions. Estimates of how often NGS leads to diagnoses or changes in management vary widely depending on the population being studied and the indications for testing. Finding a genetic variant that is classified as pathogenic may not necessarily equate with being able to predict the resultant phenotype or to give a reliable prognosis. Molecular diagnoses do not usually lead to changes in clinical management but they often end a family's diagnostic Odyssey and allow informed decisions about future reproductive choices. The likelihood that NGS will be beneficial for patients and families in the NICU remains uncertain. The goal of this paper is to highlight the implications of these ambiguities in interpreting the results of NGS. To do that, we will first review the types of cases that are admitted to NICUs and show why, at least in theory, NGS is unlikely to be useful for most NICU patients and families and may even be harmful for some, although it can help families in some cases. We then present a number of real cases in which NGS results were obtained and show that they often lead to unforeseen and unpredictable consequences. Finally, we will suggest ways to communicate with families about NGS testing and results in order to help them understand the meaning of NGS results and the uncertainty that surrounds them.

MeSH terms

  • Exome Sequencing
  • Genetic Testing / methods
  • High-Throughput Nucleotide Sequencing* / methods
  • Humans
  • Neonatology*
  • Whole Genome Sequencing