2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-Investigating the Efficacy of Targeted NGS Panels with Rapid TAT for Pediatric Patients with Narrow Differential Diagnoses

Pdf Summary

This study focuses on the efficacy of targeted next-generation sequencing (NGS) panels with rapid turnaround time (TAT) for pediatric patients with narrow differential diagnoses. Rapid genetic diagnoses are often sought for pediatric patients in the in-patient setting, but most offerings are limited to large-scale sequencing rather than targeted panels. While whole exome sequencing (WES) and whole genome sequencing (WGS) have high utility, they come with downsides such as the risk of secondary or incidental findings and considerable resource use. <br /><br />The study evaluated 11 pediatric patients with narrow differential diagnoses at the Ann & Robert H. Lurie Children’s Hospital of Chicago. Custom panels were created based on clinical presentation and history, as well as coverage on the laboratory's gene exome platform. NGS data was analyzed and reviewed by directors, genomic analysts, and genetic counselors. Pathogenic and likely pathogenic variants were confirmed, and pre- and post-test genetic counseling was provided. The average TAT for the testing was 8.5 calendar days.<br /><br />The study found that the shortened TAT of targeted NGS panels is helpful for patients who benefit from quickly establishing a diagnosis but for whom WES or WGS is unnecessary. This testing option is especially suitable for patients with a diagnosis or suspicion based on abnormal biochemical results or a relatively specific phenotype with limited genetic heterogeneity. Positive and negative diagnoses typically render additional genetic testing unnecessary. The study demonstrates a resource-conscious approach of an in-house molecular diagnostics laboratory performing expedited targeted testing for these patients and achieving expedient positive or negative genetic diagnoses.<br /><br />Overall, the study shows that targeted NGS panels with rapid TAT are effective for pediatric patients with narrow differential diagnoses, providing quick diagnoses without the need for extensive sequencing methodologies like WES or WGS.

Asset Subtitle

Presenting Author - Andy Drackley, MS, CGC; Co-Author - Pamela A. Rathbun; Co-Author - Alexander Ing, MS, CGC; Co-Author - Alissa Wlodaver, PhD; Co-Author - Joshua Baker, DO, FAAP, FACMG; Co-Author - Rachel E. Hickey, MS, CGC; Co-Author - Merlene Peter, MMSc, CGC; Co-Author - Anne M. McRae, MSGC, CGC, MS; Co-Author - Sarah Jurgensmeyer, MS, CGC; Co-Author - Kai Lee Yap, PhD; Co-Author - Carlos Prada, MD;

Meta Tag

Biochemical genetics

Clinical History

Dysmorphology

Genetic Testing

Metabolic Disorder

Methodology

NextGen Sequencing

Psychosocial Counseling Issues

Co-Author Pamela A. Rathbun

Co-Author Alexander Ing, MS, CGC

Co-Author Alissa Wlodaver, PhD

Co-Author Joshua Baker, DO, FAAP, FACMG

Co-Author Rachel E. Hickey, MS, CGC

Co-Author Merlene Peter, MMSc, CGC

Co-Author Anne M. McRae, MSGC, CGC, MS

Co-Author Sarah Jurgensmeyer, MS, CGC

Co-Author Kai Lee Yap, PhD

Co-Author Carlos Prada, MD

Presenting Author Andy Drackley, MS, CGC

Keywords

targeted next-generation sequencing

rapid turnaround time

pediatric patients

narrow differential diagnoses

genetic diagnoses

in-patient setting

whole exome sequencing

whole genome sequencing

secondary findings

incidental findings