The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening.

Despite the increased utilization of genome and exome sequencing, little is known about the actual content and process of informed consent for sequencing. We addressed this by interviewing 29 genetic counselors and research coordinators experienced in obtaining informed consent for sequencing in research and clinical settings. Interviews focused on the process and content of informed consent; patients/participants’ common questions, concerns and misperceptions; and challenges to obtaining informed consent. Content analysis of transcribed interviews revealed that the main challenges to obtaining consent related to the broad scope and uncertainty of results, and patient/ participants’ unrealistic expectations about the likely number and utility of results. Interviewees modified their approach to sessions according to contextual issues surrounding the indication for testing, type of patient, and timing of testing. With experience, most interviewees structured sessions to place less emphasis on standard elements in the consent form and technological aspects of sequencing. They instead focused on addressing misperceptions and helping patients/participants develop realistic expectations about the types and implications of possible results, including secondary findings. These findings suggest that informed consent sessions should focus on key issues that may be misunderstood by patients/participants. Future research should address the extent to which various stakeholders agree on key elements of informed consent.

Purpose As genome-scale sequencing is increasingly applied in clinical scenarios, a wide variety of genomic findings will be discovered as secondary or incidental findings, and there is debate about how they should be handled. The clinical actionability of such findings varies, thus necessitating standardized frameworks for a priori decision-making about their analysis. Methods We established a semi-quantitative metric to assess five elements of actionability: severity and likelihood of the disease outcome, efficacy and burden of intervention, and knowledge base, with a total score from 0–15. Results The semi-quantitative metric was applied to a list of putative actionable conditions, the list of genes recommended by the American College of Medical Genetics (ACMG) for return when deleterious variants are discovered as secondary/incidental findings, and a random sample of 1000 genes. Scores from the list of putative actionable conditions (median = 12) and the ACMG list (median = 11) were both statistically different than the randomly selected genes (median = 7) (two-tailed Mann-Whitney test P<0.0001). Conclusion Gene-disease pairs having a score of 11 or higher represent the top quintile of actionability. The semi-quantitative metric effectively assesses clinical actionability, promotes transparency, and may facilitate assessments of clinical actionability by various groups and in diverse contexts.

This paper summarizes the current controversies surrounding the identification and disclosure of “incidental” or “secondary” findings from genomic sequencing and the implications for genetic counseling practice. The rapid expansion of clinical sequencing has influenced the ascertainment and return of incidental findings, while empiric data to inform best practices are still being generated. Using the North Carolina Clinical Genomic Evaluation by Next Generation Exome Sequencing (NCGENES) research project as an example, we discuss the implications of different models of consent and their impact on patient decisions.