Genetic testing for the epilepsies: A systematic review

Area of Science:

• Medical Genetics
• Neurology
• Systematic Review and Meta-Analysis

Background:

• Epilepsy diagnosis is increasingly utilizing genetic testing, yet optimal strategies remain unclear.
• A decade of genetic testing advancements necessitates evidence-based guidelines for epilepsy management.

Purpose of the Study:

• To systematically review and meta-analyze the diagnostic yield of various genetic tests for epilepsy.
• To assess non-yield outcomes (NYOs) including treatment changes and prognostic information.

Main Methods:

• A systematic evidence review (SER) adhering to PRISMA guidelines was conducted.
• Meta-analyses estimated diagnostic yields for genome sequencing (GS), exome sequencing (ES), multigene panels (MGP), and chromosomal microarray (CGH/CMA).
• Non-yield outcomes were synthesized narratively.

Main Results:

• The overall diagnostic yield across all modalities was 17%.
• Genome sequencing (GS) demonstrated the highest diagnostic yield (48%), followed by ES (24%), MGP (19%), and CGH/CMA (9%).
• Developmental and epileptic encephalopathy and neurodevelopmental comorbidities were associated with increased yield.

Conclusions:

• This SER provides a comparative assessment of genetic testing yields for epilepsy, informing clinical decision-making and policy.
• Prospective evaluation of clinical and personal utility of genetic testing in epilepsy is needed.
• Standardization in reporting patient characteristics for genetic testing studies is crucial.