Genetic testing for diagnosing neurodevelopmental disorders and epilepsy: a systematic review and meta-analysis
Abstract
Identifying the genetic causes of neurodevelopmental disorders (NDDs) and epilepsy is crucial for effective treatment and genetic counseling. Our objective was to determine the diagnostic yield of chromosomal microarray (CMA) and next-generation sequencing (NGS) methods—including targeted sequencing (TS), whole-exome sequencing (WES), and whole-genome sequencing (WGS)—in individuals with NDDs or epilepsy. We systematically searched PubMed, Embase, and the Cochrane Library through August 31, 2024. Two reviewers independently screened studies and extracted data. We included studies with ≥ 10 patients (probands) diagnosed with an NDD or epilepsy who underwent CMA, TS, WES, WGS, or WES reanalysis. Methodological quality was assessed using the Newcastle–Ottawa Scale (NOS). Random-effects meta-analysis was performed to pool diagnostic yield percentages. Subgroup analyses were conducted by test modality, disorder subtype, and clinical features. A total of 416 studies (124,937 participants) met inclusion criteria. Pooled analysis showed significantly higher diagnostic yields with NGS methods compared to CMA (31.1% vs 14.8% in NDD cohorts; 28.7% vs 13.3% in epilepsy cohorts). Within NGS, WES had a higher yield than targeted gene panels (35.3% vs. 23.2% for NDDs; 34.2% vs. 24.0% for epilepsy). Diagnostic yields increased over time in more recent studies. Patients with certain clinical features had particularly high yields: NDDs with dysmorphic features (54.7%), syndromic presentations…
How strong is the evidence?
Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 124,937 participants or records.
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