Rapid whole-genome sequencing in the pediatric intensive care unit: from etiologic diagnosis to precision management-a narrative review.

Background and Objective: Children admitted to the pediatric intensive care unit (PICU) with critical illness may have underlying genetic diseases that are difficult to distinguish from sepsis, hypoxia, shock, postoperative complications, medication effects, or secondary organ injury. Rapid whole-genome sequencing (rWGS) provides a broad genomic framework within clinically actionable timeframes. This narrative review aims to summarize the diagnostic scope, implementation workflow, and clinical utility of rWGS in critically ill children. Methods: A focused literature search was conducted in PubMed using terms related to rWGS, rapid genome sequencing, rapid exome sequencing (rES), PICU, critical illness, and critically ill children. Original studies, multicenter studies, and relevant consensus documents were considered, and the primary literature search was conducted on June 25, 2026, and the final update was performed on August 20, 2026. Key Content and Findings: Evidence from critical care cohorts indicates that rapid genomic sequencing can increase etiologic diagnosis and influence clinical management through disease-specific therapy, metabolic crisis management, adjustment of antimicrobial or immunomodulatory treatment, avoidance of contraindicated interventions, reduction of low-yield procedures, prognostication, and family risk counseling. Clinical utility depends on appropriate patient selection, rapid turnaround time, trio analysis when feasible, standardized phenotyping, and multidisciplinary interpretation. Conclusions: rWGS can support precision management in critically ill children when integrated into a structured PICU genomic pathway. Nondiagnostic results and variants of uncertain significance require continued reassessment and complementary testing.