A nationwide prospective randomized trial for diagnosing developmental disorders demonstrates genome sequencing outperforms standard of care.

Genome sequencing achieves a 39.8% diagnostic yield in developmental disorders, outperforming standard care by 9.8% in a nationwide Belgian trial.

• Why it matters: Accurate diagnosis of developmental disorders remains challenging, and the clinical utility of genome sequencing (GS) compared to existing methods is debated, impacting patient care and genetic counseling.
• What they did: A prospective randomized trial compared GS with standard of care (exome sequencing and microarray) in 567 individuals, assessing diagnostic yields and variant detection capabilities across multiple centers.
• The result: GS demonstrated a higher diagnostic yield, especially for single nucleotide variants and indels, and identified non-coding pathogenic variants, supporting its broader clinical adoption for developmental disorders.