The Impact of Rapid Exome Sequencing on Medical Management of Critically Ill Children

Objectives To evaluate the clinical utility of rapid exome sequencing (rES) in critically ill children with likely genetic disease using a standardized process at a single institution. To provide evidence that rES with should become standard of care for this patient population. Study design We implemented a process to provide clinical-grade rES to eligible children at a single institution. Eligibility included: a) recommendation of rES by a consulting geneticist, b) monogenic disorder suspected, c) rapid diagnosis predicted to affect inpatient management, d) pre-test counseling provided by an appropriate provider, and e) unanimous approval by a committee of 4 geneticists. Trio exome sequencing was sent to a reference laboratory that provided verbal report within 7-10 days. Clinical outcomes related to rES were prospectively collected. Input from geneticists, genetic counselors, pathologists, neonatologists and critical care pediatricians was collected to identify changes in management related to rES. Results 54 patients were eligible for rES over a 34 month study period. 46 of these underwent rES, 24 of which (52%) had at least one change in management related to rES. In 20 (43%) patients a molecular diagnosis was achieved, demonstrating that non-diagnostic exomes could change medical management in some cases. 84% were under 1 month old at rES request and mean turnaround time was 9 days. Conclusions rES testing has a significant impact on the management of critically ill children with suspected monogenic disease and should be considered standard of care for tertiary institutions who can provide coordinated genetics expertise.