Citywide implementation of a rapid whole-genome sequencing program for critically ill pediatric patients.

Trio rapid whole-genome sequencing organized at citywide scale within centralized neonatal and pediatric intensive care units.

Little Falcon is a rapid whole-genome sequencing program implemented citywide in Dubai, within centralized neonatal and pediatric intensive care units. One hundred critically ill patients from 18 Middle Eastern and Asian countries underwent trio rapid sequencing with a median turnaround time of 3.4 days. Overall diagnostic yield was 53% (95% CI 43.3-62.5), rising to 80% in consanguineous families (P < 0.001); multiple molecular findings were identified in 12% of patients, including dual diagnoses in 5%, with additional newborn screening-relevant variants in 4% and American College of Medical Genetics secondary or incidental findings in 3%. Sequencing led to clinically meaningful management changes in 53% of patients, with (n = 45) or without (n = 8) a molecular diagnosis, and altered disease trajectories in 16%. Against a matched historical cohort receiving standard genetic testing, rapid sequencing reduced diagnostic time (3.4 versus 38 days, P < 0.001), increased yield (53% versus 30%, P < 0.01) and improved clinical management (53% versus 18%, P < 0.001).

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

The value of this work is not the 53% yield, now expected in pediatric intensive care, but the demonstration that a 3.4-day median turnaround holds at the scale of an entire health system rather than a single expert centre. The 80% yield in consanguineous families is a reminder that a program's yield depends first on the structure of the population served: that figure does not transfer directly to Europe. The historical-cohort comparison remains the methodological weak point, but a shift from 38 to 3.4 days is of a magnitude that selection bias does not explain.

Analysis by Dr Thibaut Benquey