ClinGen’s Pediatric Actionability Working Group: Clinical actionability of secondary findings from genome-scale sequencing in children and adolescents

Hunter, Jessica Ezzell; Jenkins, Charisma L.; Bulkley, Joanna E.; Gilmore, Marian J.; Lee, Kristy; Pak, Christine M.; Wallace, Kathleen; Buchanan, Adam H.; Foreman, Ann Katherine M.; Freed, Amanda S.; Goehringer, Scott; Manickam, Kandamurugu; Meeks, Naomi; Ramos, Erin M.; Shah, Neethu; Steiner, Robert D.; Subramanian, Sai Lakshmi; Trotter, Tracy L.; Webber, Elizabeth M.; Williams, Marc S.; Goddard, Katrina A.B.; Powell, Bradford C.

doi:10.1016/j.gim.2022.02.019

Cited by 5 publications

(2 citation statements)

References 21 publications

(30 reference statements)

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“…"Actionable" has been defined as follows: "if there are available preventive and/or treatment measures and the disorder has either (i) childhood onset and such measures are therefore initiated in childhood, or (ii) adult onset, but such measures have been demonstrated to be effective when started in childhood" [72]. As of 2021, the Clinical Genome Resource Paediatric Actionability Working Group was able to provide guidelines regarding return of results related to 143 genes, on the basis of actionability [73].…”

Section: Which Result?mentioning

confidence: 99%

ELSI challenges with children in Translational Medicine

Casati,

Ellul

2024

Contemporary Issues in Clinical Bioethics - Medical, Ethical and Legal Perspectives

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Paediatric translational research deals mainly with genomics of biological samples. It has benefitted substantially from developments in new technologies and from international collaboration to access and use large cohorts of banked biological samples and associated data. However, there are still significant ELSI (ethical, legal and societal implications) challenges that need to be addressed before we can move smoothly from the “bench” to the “bedside” to the “community”. In this chapter we shall concentrate on the intertwined ethical and legal issues regarding informed assent/consent of minors and the return of genomic results to minors and families. This leads to the societal issues faced in minor engagement and empowerment. We will then emphasise the need for healthcare integrated biobanking to maximise use of samples and data and so facilitate translational research.

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Section: Which Result?mentioning

confidence: 99%

ELSI challenges with children in Translational Medicine

Casati,

Ellul

2024

Contemporary Issues in Clinical Bioethics - Medical, Ethical and Legal Perspectives

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“…Partitioning the genome into interpretable groupings based on the clinical actionability and natural history characteristics of genetic conditions can facilitate informed decision-making and preference setting by individuals and parents [ 28 ]. ABGS will rely on a semi-quantitative metric (SQM) for scoring clinical actionability based on five key parameters (the severity and likelihood of disease manifestations, the efficacy and acceptability of interventions, and a knowledge base about the condition) [ 29 ] that was previously developed by our research group and subsequently adopted with minor modifications by the ClinGen Actionability and Pediatric Actionability Working Groups [ 30 , 31 ]. We utilized this approach to define a subset of conditions that qualified for disclosure to research participants as a “next-generation sequencing newborn screen” [ 32 ] and further analyzed SQM scores for a comparison of commercial panels that are being offered to parents as expanded newborn screening options [ 33 ].…”

Section: Identifying Appropriate Conditions For Screening During Chil...mentioning

confidence: 99%

Age-Based Genomic Screening during Childhood: Ethical and Practical Considerations in Public Health Genomics Implementation

Milko

Berg

2023

IJNS

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Genomic sequencing offers an unprecedented opportunity to detect inherited variants that are implicated in rare Mendelian disorders, yet there are many challenges to overcome before this technology can routinely be applied in the healthy population. The age-based genomic screening (ABGS) approach is a novel alternative to genome-scale sequencing at birth that aims to provide highly actionable genetic information to parents over the course of their child’s routine health care. ABGS utilizes an established metric to identify conditions with high clinical actionability and incorporates information about the age of onset and age of intervention to determine the optimal time to screen for any given condition. Ongoing partnerships with parents and providers are instrumental to the co-creation of educational resources and strategies to address potential implementation barriers. Implementation science frameworks and informative empirical data are used to evaluate strategies to establish this unique clinical application of targeted genomic sequencing. Ultimately, a pilot project conducted in primary care pediatrics clinics will assess patient and implementation outcomes, parent and provider perspectives, and the feasibility of ABGS. A validated, stakeholder-informed, and practical ABGS program will include hundreds of conditions that are actionable during infancy and childhood, setting the stage for a longitudinal implementation that can assess clinical and health economic outcomes.

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