Rapid Genome Sequencing in the Critically Ill.

Abstract

Genetic conditions, already recognized as a major cause of morbidity and mortality in children, are increasingly the focus of diagnostic questions in neonatal and pediatric intensive care units (NICU/PICU)6. When a genetic disorder is suspected but a specific diagnosis or targeted test is unavailable, genome-wide sequencing approaches, such as exome sequencing (ES) and genome sequencing (GS), can interrogate a wide range of potential diagnoses within a single test. However, standard ES and GS tests are problematic owing to turnaround times measured in weeks to months, which are too long to benefit the most acutely ill children. In recent years, rapid ES and rapid genome sequencing (rGS) options have been developed that can provide results within a greatly accelerated time frame.\n\nStudies are beginning to show the potential widespread clinical impact of offering rapid genome-wide sequencing tests as a first-tier assay for critically ill infants in the NICU/PICU (1–3). A study recently published by Farnaes et al. (1) demonstrated the potential cost savings and improved patient management when rGS was provided to 42 hospitalized infants in the NICU/PICU without a diagnosis but with features suggestive of a genetic etiology. Eighteen (43%) of the newborns received a genetic diagnosis by rGS. Thirteen diagnosed newborns (72%) had changes in clinical management, some significantly reducing morbidity with changes in medication and surgical plan as a direct result of the rGS findings. Despite the high cost of rGS, its application in the NICU/PICU ultimately reduced inpatient costs by over $800000 for 6 infants in whom a matched control was available for comparison or a major procedure was avoided. This study is among the first to quantify the potential cost savings with rGS.\n\nThere is little doubt that future studies of rGS will demonstrate consistent improvement in diagnostic yield and cost savings …