Diagnostic and clinical utility of exome sequencing and chromosomal microarray in children with GDD/iD: a meta-analysis.
Maliwan Tengsujaritkul, Orawan Louthrenoo, Narueporn Likhitweerawong et al.
✦ AI-curated · Sources linked
In 30 seconds
This systematic review and meta-analysis assessed the diagnostic utility of whole exome sequencing (WES), chromosomal microarray (CMA), and whole genome sequencing in children with unexplained global developmental delay or intellectual disability (GDD/ID). Across 102 studies involving 55,752 children, pooled diagnostic yield was higher for WES than CMA: 0.37 (95% CI: 0.33-0.41) versus 0.19 (95% CI: 0.16-0.21). WES also had higher diagnostic rates in same-sample and different-sample comparisons. Only one study evaluated whole genome sequencing, reporting a yield of 0.27.
Key findings
- Pooled diagnostic yield was 0.37 (95% CI: 0.33-0.41) for WES and 0.19 (95% CI: 0.16-0.21) for CMA.
- WES had higher diagnostic rates than CMA in same-sample comparisons (OR = 2.27, 95% CI: 1.08-4.78) and different-sample comparisons (OR = 1.65, 95% CI: 1.15-2.37).
- Diagnostic utility did not differ significantly between isolated GDD/ID and GDD/ID with comorbidities.
- Only one included study assessed whole genome sequencing, reporting a diagnostic yield of 0.27.
Why it matters
A higher diagnostic yield may help identify genetic explanations for GDD/ID in more children and inform diagnostic evaluation. The findings support consideration of WES in this population, while the substantial heterogeneity across studies and limited evidence for whole genome sequencing warrant careful interpretation.
What to keep in mind
Diagnostic yields were highly heterogeneous across studies (I² = 93% for WES and 95% for CMA). Evidence for whole genome sequencing was limited to one study.