Genetic disorders associated with neurodevelopmental disorders in children in Saudi Arabia: A systematic review and meta-analysis

Abstract

Objectives: High consanguinity in Saudi Arabia has shaped the genetic architecture of pediatric neurodevelopmental disorders (NDDs), potentially increasing autosomal recessive (AR) etiologies and the diagnostic yield of exome-based testing. This study aims to synthesize genetic disorders reported in Saudi children with NDDs and to quantify the pooled diagnostic yield of clinical exome sequencing/whole-exome sequencing (CES/WES). Methods: We conducted a systematic review and meta-analysis registered in PROSPERO (CRD420251250437) following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Diagnostic yield was pooled as a proportion using a random-effects model with logit transformation; between-study variance (τ2) was estimated using the restricted maximum likelihood method, and pooled estimates were back-transformed to the proportion scale for reporting. Results: Five sequencing cohorts contributed to the meta-analysis. The pooled CES/WES diagnostic yield was 0.43 (95% confidence interval: 0.36–0.50) with substantial heterogeneity (I 2 = 87.8%, p < 0.0001). The 95% prediction interval was 0.20–0.69, indicating wide variability across tertiary referral cohorts. In the largest cohort, solved cases were predominantly AR (77.2%), autosomal dominant (20.0%), and X-linked (3.9%); yield was higher in consanguineous than non-consanguineous families (53% vs. 39%). Funnel plot inspection and Egger’s test ( p = 0.815) did not suggest publication bias, although interpretation is limited by the small number of included studies. Conclusion: Saudi pediatric NDD cohorts show a high CES/WES diagnostic yield consistent with a strong AR contribution in a high-consanguinity population; however, yields vary substantially by cohort and clinical context.