Rapid Whole-Genome Sequencing Diagnoses Nearly Half of Pediatric Neurology Inpatients

Rapid whole-genome sequencing (WGS) has primarily been studied in neonatal and pediatric intensive care populations. This retrospective cohort study assessed its utility in 175 pediatric inpatients with unexplained neurologic presentations at a tertiary medical center between June 2022 and January 2026. Participants were admitted to neonatal or pediatric intensive care units or general wards; median age was 4 months. The primary endpoint was initial diagnostic yield for findings concordant with the presenting phenotype.

Initial rapid WGS established phenotype-concordant diagnoses in 79 children (45.1%). Yield was higher in nonneonates than neonates: 52.7% versus 36.6%. Preliminary results returned in a mean of 4.0 days and final reports in 10.4 days. Reanalysis of 14 initially nondiagnostic cases identified three additional diagnoses, increasing cumulative yield to 82 of 175 (46.9%). Management changed in 54 of these 82 children (65.9%) and in eight of 33 children with positive findings not concordant with their presentation.

Family history had the strongest adjusted association with diagnosis (adjusted odds ratio, 6.46; 95% CI, 3.23–12.93), followed by multisystem involvement and congenital anomalies or dysmorphism. The findings support considering rapid WGS early in selected pediatric neurologic evaluations. However, the retrospective, single-center design limits generalizability, and reported management changes do not establish improved clinical outcomes. Reanalysis was selective rather than systematic; this report is based on the abstract, without full-text review.