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...
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Genome Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13073-022-01139-2 |
| _version_ | 1811211135720882176 |
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| author | Kevin M. Bowling Michelle L. Thompson Melissa A. Kelly Sarah Scollon Anne M. Slavotinek Bradford C. Powell Brian M. Kirmse Laura G. Hendon Kyle B. Brothers Bruce R. Korf Gregory M. Cooper John M. Greally Anna C. E. Hurst |
| author_facet | Kevin M. Bowling Michelle L. Thompson Melissa A. Kelly Sarah Scollon Anne M. Slavotinek Bradford C. Powell Brian M. Kirmse Laura G. Hendon Kyle B. Brothers Bruce R. Korf Gregory M. Cooper John M. Greally Anna C. E. Hurst |
| author_sort | Kevin M. Bowling |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T05:07:37Z |
| format | Article |
| id | doaj.art-e4cc7a2958a74910939d83b6cfc1eb15 |
| institution | Directory Open Access Journal |
| issn | 1756-994X |
| language | English |
| last_indexed | 2024-04-12T05:07:37Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Medicine |
| spelling | doaj.art-e4cc7a2958a74910939d83b6cfc1eb152022-12-22T03:46:51ZengBMCGenome Medicine1756-994X2022-11-0114111710.1186/s13073-022-01139-2Return of non-ACMG recommended incidental genetic findings to pediatric patients: considerations and opportunities from experiences in genomic sequencingKevin M. Bowling0Michelle L. Thompson1Melissa A. Kelly2Sarah Scollon3Anne M. Slavotinek4Bradford C. Powell5Brian M. Kirmse6Laura G. Hendon7Kyle B. Brothers8Bruce R. Korf9Gregory M. Cooper10John M. Greally11Anna C. E. Hurst12HudsonAlpha Institute for BiotechnologyHudsonAlpha Institute for BiotechnologyHudsonAlpha Clinical Services Lab, LLC, HudsonAlpha Institute for BiotechnologyDepartment of Pediatrics, Baylor College of MedicineDepartment of Pediatrics, University of CaliforniaDepartment of Genetics, University of North Carolina at Chapel HillDepartment of Pediatrics, University of Mississippi Medical CenterDepartment of Pediatrics, University of Mississippi Medical CenterNorton Children’s Research Institute Affiliated with UofL School of MedicineDepartment of Genetics, University of Alabama at BirminghamHudsonAlpha Institute for BiotechnologyDepartment of Genetics, Albert Einstein College of MedicineDepartment of Genetics, University of Alabama at BirminghamAbstract 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.https://doi.org/10.1186/s13073-022-01139-2Incidental findingsGenomicsGenetic testingPediatricsDisease severityPersonal utility |
| spellingShingle | Kevin M. Bowling Michelle L. Thompson Melissa A. Kelly Sarah Scollon Anne M. Slavotinek Bradford C. Powell Brian M. Kirmse Laura G. Hendon Kyle B. Brothers Bruce R. Korf Gregory M. Cooper John M. Greally Anna C. E. Hurst Return of non-ACMG recommended incidental genetic findings to pediatric patients: considerations and opportunities from experiences in genomic sequencing Genome Medicine Incidental findings Genomics Genetic testing Pediatrics Disease severity Personal utility |
| title | Return of non-ACMG recommended incidental genetic findings to pediatric patients: considerations and opportunities from experiences in genomic sequencing |
| title_full | Return of non-ACMG recommended incidental genetic findings to pediatric patients: considerations and opportunities from experiences in genomic sequencing |
| title_fullStr | Return of non-ACMG recommended incidental genetic findings to pediatric patients: considerations and opportunities from experiences in genomic sequencing |
| title_full_unstemmed | Return of non-ACMG recommended incidental genetic findings to pediatric patients: considerations and opportunities from experiences in genomic sequencing |
| title_short | Return of non-ACMG recommended incidental genetic findings to pediatric patients: considerations and opportunities from experiences in genomic sequencing |
| title_sort | return of non acmg recommended incidental genetic findings to pediatric patients considerations and opportunities from experiences in genomic sequencing |
| topic | Incidental findings Genomics Genetic testing Pediatrics Disease severity Personal utility |
| url | https://doi.org/10.1186/s13073-022-01139-2 |
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