A Model Program for Translational Medicine in Epilepsy Genetics

Abstract

Recent technological advances in gene sequencing have led to a rapid increase in gene discovery in epilepsy. However, the ability to assess pathogenicity of variants, provide functional analysis, and develop targeted therapies has not kept pace with rapid advances in sequencing technology. Thus, although clinical genetic testing may lead to a specific molecular diagnosis for some patients, test results often lead to more questions than answers. As the field begins to focus on therapeutic applications of genetic diagnoses using precision medicine, developing processes that offer more than equivocal test results is essential. The success of precision medicine in epilepsy relies on establishing a correct genetic diagnosis, analyzing functional consequences of genetic variants, screening potential therapeutics in the preclinical laboratory setting, and initiating targeted therapy trials for patients. The authors describe the structure of a comprehensive, pediatric Epilepsy Genetics Program that can serve as a model for translational medicine in epilepsy.

Keywords: epilepsy genetics; precision medicine; translational medicine.

Conflict of interest statement

Declaration of Conflicting Interests

AP serves on the Scientific Advisory Board of the Dravet Syndrome Foundation and the Professional Advisory Board of the Patient Centered Outcomes Research Institute (PCORI)-funded Rare Epilepsy Network.

Figures

Figure 1

Schematic of Epilepsy Genetics Clinic consult of a patient who has had previous genetic testing. Includes potential pathways based on clinical findings, treatment options, and research enrollment. Abbreviations: EGC, Epilepsy Genetics Clinic; EGI, Epilepsy Genetics Initiative; WES, whole exome sequencing.