Customized multigene panels in epilepsy: the best things come in small packages

Area of Science:

• Genetics
• Neurology
• Molecular Diagnostics

Background:

• Next-generation sequencing panels are increasingly vital for epilepsy genetic diagnosis, yielding extensive data but lacking standardized design and patient selection criteria.
• Current challenges include optimizing cost-benefit ratios and diagnostic efficiency, despite the rise of whole-exome sequencing.

Purpose of the Study:

• To systematically review existing epilepsy gene panels in scientific literature.
• To identify optimal patient selection criteria for gene-panel analysis.
• To define an "ideal" gold-standard panel for epilepsy, including pathogenic and actionable genes.

Main Methods:

• Systematic literature review of targeted gene panels for epilepsy.
• Analysis of gene variant data, clinically actionable genes, and International League Against Epilepsy (ILAE) recommendations.
• Evaluation of panel size and patient selection strategies.

Main Results:

• Customized gene panels are most effective when limited to rationally selected gene pools and applied to carefully selected patients, particularly those with complex epilepsy.
• A 64-gene panel, comprising 45 genes with known pathogenic variants, 32 clinically actionable genes, and 21 ILAE-recommended genes, emerges as a potential "ideal" core set.
• This proposed panel aims to maximize diagnostic efficiency and cost-effectiveness while aiding gene prioritization.

Conclusions:

• Rational selection of genes and patients enhances the diagnostic power of epilepsy gene panels.
• A 64-gene core panel represents a balanced approach for efficient and cost-effective genetic testing in epilepsy.
• Further standardization in panel design and patient selection can optimize genetic diagnosis for epilepsy.