Next-Generation Sequencing (NGS) is being used with increasing frequency to diagnose neurodevelopmental disorders including epilepsy, autism spectrum disorder (ASD), and intellectual disability. With more studies available now compared to 10 years ago, a group of genetic researchers performed a systematic review and meta-analysis of the NGS success rate in diagnosing neurodevelopmental disorders in Epilepsia.
The researchers analyzed PubMed literature through May 2020 using the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocol. A total of used 103 studies that included 32,331 individuals were utilized.
Overall diagnostic yield for neurodevelopmental disorder sequencing studies was 23.7% (95% CI 22%–26%), weighted by the number of cases in each study. The highest diagnostic yield was observed for intellectual disability (28.2%, 95% CI 22%–35%), followed by epilepsy (24%, 95% CI 22%–27%) and autism spectrum disorder (17.1%, 95% CI 11%–25%). The researchers also analyzed seizure type and diagnostic yield by sequencing technology.
Limitations include that diagnostic yield may be underestimated in some studies as all studies used the same guidelines. There were no studies from Africa, Latin America, or India. That said, the authors believe their meta-analysis can guide policy makers and healthcare providers.
While many results somewhat matched previous, smaller studies, the researchers’ diagnostic yield for exome sequencing and epilepsy was much lower (27.2% vs 45%). Also, the fact that the current study is three to four times larger may explain the lower diagnostic yield for exome sequencing and epilepsy.
Stefanski A, Calle-López Y, Leu C, Pérez-Palma E, Pestana-Knight E, Lal D. Clinical sequencing yield in epilepsy, autism spectrum disorder, and intellectual disability: A systematic review and meta-analysis. Epilepsia. Published online November 17, 2020. doi:10.1111/epi.16755