Katherine Rodriguez, MD (she/her/hers)
Fellow Physician
Rady Children's Hospital - San Diego
San Diego, California
Disclosure information not submitted.
Erica Sanford Kobayashi, MD
Attending Physician
University of California, San Diego, United States
Disclosure information not submitted.
Nicole Coufal, MD, PhD
Attending Physician, Assistant Professor
University of California - San Diego, Rady Children's Hospital, United States
Disclosure information not submitted.
David Dimmock, MD
Senior Medical Director
Rady Children's Institute for Genomic Medicine, United States
Disclosure information not submitted.
Stephen Kingsmore, MD, DSc
President/CEO
Rady Children's Institute for Genomic Medicine, United States
Disclosure information not submitted.
Title: Impact of Rapid Whole Genome Sequencing in the PICU
Introduction:
Genetic disorders are a significant contributor to morbidity and mortality in pediatric critical care. Recently, rapid whole genome sequencing (rWGS) has drastically impacted the care provided in neonatal intensive care units. There remains a population of undiagnosed patients with rare genetic diseases who present critically ill to the pediatric intensive care unit (PICU) and the application of rWGS in this setting is not yet fully described. This study evaluates the utility of rWGS in the PICU.
Methods:
This is a retrospective cohort study conducted at a single tertiary children’s hospital from August 2016 to July 2021. Children were nominated for rWGS by the care team when etiology of illness was unclear, a priori suspicion of a genetic disorder was not required. Children who received rWGS in the PICU age 1 month to 18 years were eligible for inclusion. rWGS with targeted phenotype-driven analysis was performed. Clinical diagnostic utility was assessed via provider surveys of PICU physicians and electronic health record review.
Results:
Sixty cases were identified to meet the inclusion criteria making this the largest cohort of rWGS in the PICU in the United States. Diagnostic sensitivity was 42% (25 of 60). The molecular diagnosis was considered to completely describe the phenotypic presentation in 80% of diagnosed cases. Over the 5-year study period, test turnaround time improved from 13.6 to 3.3 days. The majority of patients with diagnostic genomes (64%) had no known dysmorphic features or developmental delay. rWGS molecular diagnosis was responsible for changes in management in 76% of diagnosed cases. PICU provider surveys for a subset of patients identified clinical utility specifically in diagnosis, medical decision making, referrals to palliative care, and changes in code status.
Conclusions:
In this cohort, most of the diagnosed patients did not have features classically associated with genetic disorders, making them difficult to identify. Molecular diagnosis of genetic disorders in the PICU population frequently results in changes in care during hospitalization, making rapid case identification and testing imperative. Increasing availability of rWGS can significantly impact patient care and assist families in making difficult decisions during times of critical illness.