Rapid Whole-Genome Sequencing in Pediatric Neurology Inpatients.

This retrospective cohort study, conducted at a tertiary centre from June 2022 to January 2026, covers 175 inpatients (82 neonates, 93 non-neonates) with an unexplained neurological presentation who underwent rapid genome sequencing (rWGS) as trio (77.8%), duo or singleton. Initial rWGS established a phenotype-concordant diagnosis in 79 children (45.1%), more often in non-neonates (52.7%) than neonates (36.6%), with preliminary results at a mean of 4.0 days. Reanalysis of 14 non-diagnostic cases yielded 3 additional diagnoses (cumulative yield 46.9%), and management changed in 54 of 82 concordant cases (65.9%). Family history was the factor most strongly associated with diagnosis (adjusted OR 6.46; 95% CI 3.23-12.93).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

A 45% yield and a management change in two thirds of diagnosed cases support early rWGS in inpatient paediatric neurology, beyond intensive care alone. The limits are those of a retrospective single-centre series with patient selection, and the association of clinical factors with diagnosis should guide selection rather than restrict it. The gain from reanalysis (3 diagnoses in 14 cases) is a reminder that genome sequencing is not a single-read test.

Analysis by Dr Thibaut Benquey