Advantages of Exome Sequencing Over Panel Testing for Individuals With a Seizure Indication

Area of Science:

• Genetics
• Neurology
• Molecular Diagnostics

Background:

• Epilepsy and seizures are complex neurological disorders with diverse genetic etiologies.
• Accurate genetic diagnosis is crucial for effective patient management and treatment strategies.
• Current diagnostic approaches include panel testing and whole exome sequencing.

Purpose of the Study:

• To compare the diagnostic yield and clinical utility of exome sequencing versus traditional epilepsy panel testing.
• To evaluate the advantages of exome sequencing for patients with unexplained seizures.
• To assess the potential of exome sequencing as a first-tier genetic test.

Main Methods:

• Retrospective analysis of diagnostic outcomes from over 16,000 individuals with seizure history.
• Comparison of variants identified by exome sequencing with genes included in commercial epilepsy panels.
• Evaluation of diagnostic information gained by exome sequencing in patients with prior non-diagnostic panel tests.

Main Results:

• Exome sequencing identified diagnostic variants in 24.6% of patients, covering 778 seizure-related genes.
• A significant proportion of diagnostic cases (52%-63%) would have been missed by current epilepsy panels.
• Exome sequencing provided new diagnostic information in 74.2% of patients with prior non-diagnostic panels and identified actionable variants in 17.9% of cases.

Conclusions:

• Exome sequencing demonstrates superior diagnostic capabilities compared to epilepsy panels for unexplained seizures.
• It offers higher diagnostic rates and identifies clinically relevant findings, including those unrelated to seizures.
• Exome sequencing should be considered a primary diagnostic tool for patients with unexplained seizures due to its comprehensive genetic insights and clinical benefits.