Practical NeurologyA Guide to Genetic Testing in Pediatric Epilepsy

Unraveling the Genetic Underpinnings of Pediatric Epilepsy: A Comprehensive Review of Diagnostic Tools and Their Clinical Implications

This comprehensive review discusses the pivotal role of genetic testing in diagnosing and managing pediatric epilepsy. It stresses the significance of multigene epilepsy panels, whole-exome sequencing (WES), whole-genome sequencing (WGS), and chromosomal microarray analysis (CMA) in providing diagnostic clarity, therapeutic guidance, and valuable prognostic information.

Key Points

• Genetic factors play a crucial role in the pathogenesis of unexplained pediatric epilepsy, with an estimated 30% to 40% of cases having a genetic etiology.
• Multigene epilepsy panels, using Next-Generation Sequencing (NGS) technology, streamline the identification of known causative variants within epilepsy-related genes.
• Whole-Exome Sequencing (WES) and Whole-Genome Sequencing (WGS) allow for continual reanalysis of genomic data over time, aiding in the diagnosis of rare disorders or identifying candidate genes potentially associated with epilepsy.
• Chromosomal Microarray Analysis (CMA) enables the detection of submicroscopic chromosomal imbalances, such as deletions, duplications, and copy number variations, across an individual’s genome.
• Genetic testing faces significant challenges in terms of accessibility and results interpretation, particularly for Variants of Uncertain Significance (VUS).

HCN Medical Memo
According to a study published in Nature Communications in 2020, researchers have identified 16 new genetic risk factors for epilepsy, bringing the total number of risk genes for epilepsy to 44.

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