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

Amanda S. Freed, Sarah V. Clowes Candadai, Megan C. Sikes, Jenny Thies, Heather M. Byers, Jennifer N. Dines, Mesaki Kenneth Ndugga-Kabuye, Mallory B. Smith, Katie Fogus, Heather C. Mefford, Christina Lam, Margaret P. Adam, Angela Sun, John K. McGuire, Robert DiGeronimo, Katrina M. Dipple, Gail H. Deutsch, Zeenia C. Billimoria, James T. Bennett

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Objectives: To evaluate the clinical usefulness 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) pretest 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: There were 54 patients who were eligible for rES over a 34-month study period. Of these patients, 46 underwent rES, 24 of whom (52%) had at least 1 change in management related to rES. In 20 patients (43%), a molecular diagnosis was achieved, demonstrating that nondiagnostic exomes could change medical management in some cases. Overall, 84% of patients were under 1 month old at rES request and the 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.

Original languageEnglish
Pages (from-to)202-212.e1
JournalJournal of Pediatrics
StatePublished - Nov 2020


  • ICU
  • clinical usefulness
  • copy number variants (CNVs)
  • critically ill
  • exome sequencing
  • genomic testing
  • rare disease
  • secondary findings
  • utilization management


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