Genetic disorders associated with neurodevelopmental disorders in children in Saudi Arabia: A systematic review and meta-analysis
Faisal Awad Albalawi, Majed Mohammed Alshehri, Mohammed Saeed Almasodi, Mohammed Abdullah Alrabie, Anas Ali Asiri, Alwaleed Ali Alshehri, Meshari Tael Althuwaybi, Abdullah Mohammed Alahmri, Omar Ahmed Asiri, Asim Hamoud AlanaziObjectives:
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.