@article{e961fcd03abf4392907108bc54d97421,
title = "Return of non-ACMG recommended incidental genetic findings to pediatric patients: considerations and opportunities from experiences in genomic sequencing",
abstract = "Background: The uptake of exome/genome sequencing has introduced unexpected testing results (incidental findings) that have become a major challenge for both testing laboratories and providers. While the American College of Medical Genetics and Genomics has outlined guidelines for laboratory management of clinically actionable secondary findings, debate remains as to whether incidental findings should be returned to patients, especially those representing pediatric populations. Methods: The Sequencing Analysis and Diagnostic Yield working group in the Clinical Sequencing Evidence-Generating Research Consortium has collected a cohort of pediatric patients found to harbor a genomic sequencing-identified non-ACMG-recommended incidental finding. The incidental variants were not thought to be associated with the indication for testing and were disclosed to patients and families. Results: In total, 23 {"}non-ACMG-recommended incidental findings were identified in 21 pediatric patients included in the study. These findings span four different research studies/laboratories and demonstrate differences in incidental finding return rate across study sites. We summarize specific cases to highlight core considerations that surround identification and return of incidental findings (uncertainty of disease onset, disease severity, age of onset, clinical actionability, and personal utility), and suggest that interpretation of incidental findings in pediatric patients can be difficult given evolving phenotypes. Furthermore, return of incidental findings can benefit patients and providers, but do present challenges. Conclusions: While there may be considerable benefit to return of incidental genetic findings, these findings can be burdensome to providers and present risk to patients. It is important that laboratories conducting genomic testing establish internal guidelines in anticipation of detection. Moreover, cross-laboratory guidelines may aid in reducing the potential for policy heterogeneity across laboratories as it relates to incidental finding detection and return. However, future discussion is required to determine whether cohesive guidelines or policy statements are warranted.",
keywords = "Actionability, Age of onset, Disease severity, Genetic testing, Genomics, Incidental findings, Pediatrics, Penetrance, Personal utility",
author = "Bowling, {Kevin M.} and Thompson, {Michelle L.} and Kelly, {Melissa A.} and Sarah Scollon and Slavotinek, {Anne M.} and Powell, {Bradford C.} and Kirmse, {Brian M.} and Hendon, {Laura G.} and Brothers, {Kyle B.} and Korf, {Bruce R.} and Cooper, {Gregory M.} and Greally, {John M.} and Hurst, {Anna C.E.}",
note = "Funding Information: This work was supported by grants from the US National Human Genome Research Institute (NHGRI), including U01HG007301 (SouthSeq), U01HG009599 (PEGS), U01HG006485 (KidsCanSeq). COAGS was funded by internal institutional support from Children{\textquoteright}s of Alabama. All funding sources provided support for the study design, data collection, analysis, and interpretation of data and manuscript writing. 3 Funding Information: The Clinical Sequencing Evidence-Generating Research Consortium (CSER), funded by the National Human Genome Research Institute (NHGRI), the National Cancer Institute (NCI), and the National Institute on Minority Health and Health Disparities (NIMHD), is a national multi-site research program focused on engaging traditionally underrepresented populations in genomic research and implementing genomic sequencing into the clinical care of diverse and medically underserved populations. This study included three CSER-funded studies as well as one other research study at a CSER-participating institution, and together, the four studies have identified 23 IFs across 21 pediatric patients. Our laboratories have taken a case-by-case approach in identifying, interpreting, and returning IFs to pediatric patients and families, and this approach varied by site. In doing so, we have gained insight into the types of IFs that may be discovered when using genomic sequencing in younger patients, their potential for benefit, and the considerations that must be taken when deciding whether to return them to patients. Funding Information: SouthSeq [], KidsCanSeq, PEGS [], and COAGS are research studies aimed at determining the benefit of using genomic sequencing (ES/GS) in pediatric patients to identify genetic variation underlying disease etiology (Table ). SouthSeq, KidsCanSeq, and PEGS are funded by the NIH as part of the CSER consortium. 3 3 Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1186/s13073-022-01139-2",
language = "English",
volume = "14",
journal = "Genome medicine",
issn = "1756-994X",
number = "1",
}