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

Genome sequencing has a diagnostic yield of 39.8% in patients with developmental disorders, outperforming standard care which has a yield of 30%, in a nationwide Belgian trial.

• Why it matters: Accurate diagnosis of developmental disorders remains challenging, and the clinical utility of genome sequencing compared to existing methods is debated, impacting patient care and genetic counseling.
• What they did: A prospective randomized trial compared genome sequencing with standard of care (exome plus microarray or shallow genome sequencing) in 567 individuals with unexplained developmental disorders, assessing diagnostic yields and variant detection.
• The result: Genome sequencing demonstrated a higher diagnostic yield, mainly due to increased detection of single nucleotide variants and indels (+8.7%), and identified three non-coding variants, suggesting its superior utility in diagnosing developmental disorders.