Molecular Diagnosis of Epilepsy in Clinical Practice
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Major advances in genetics allow us to uncover genetic causes of epilepsy and influence therapeutic decisions. As precision medicine becomes a focus for bio-health industry, laws related to next generation sequencing are improving and its application will continue to expand. Although genetic testing can be considered for anyone who is suspected to have a genetic cause, the most suitable indication is drug-resistant epilepsy. Epileptic patients who have genetic testing can be classified into three groups: (1) patients with defined phenotypes suggesting monogenic epilepsy syndrome; (2) patients with neuropsychiatric comorbidities or dysmorphic features; and (3) patients with undefined phenotypes with multiple candidate genes. Applicable genetic testing methods for epilepsy are as follows: Sanger sequencing, chromosome microarray, targeted gene panels, whole exome sequencing, and whole genome sequencing. Sanger sequencing is indicated for patients with defined phenotypes by a single gene mutation. Chromosome microarray is recommended as part of the initial evaluation of unexplained epilepsy, particularly among patients with associated neuropsychiatric comorbidities or dysmorphic features. Next generation sequencing can be informative in patients with undefined phenotypes with multiple candidate genes. Targeted gene panels are a cost-effective alternative to both Sanger sequencing and whole exome sequencing for the genetic diagnosis of epilepsy. There are, however, social, ethical and even financial hurdles to overcome in the transition of next generation sequencing technology into the clinic. This review focuses on recent transformation of epilepsy genetics and suggests a strategy for actual clinical practice.
Abstract
Major advances in genetics allow us to uncover genetic causes of epilepsy and influence therapeutic decisions. As precision medicine becomes a focus for bio-health industry, laws related to next generation sequencing are improving and its application will continue to expand. Although genetic testing can be considered for anyone who is suspected to have a genetic cause, the most suitable indication is drug-resistant epilepsy. Epileptic patients who have genetic testing can be classified into three groups: (1) patients with defined phenotypes suggesting monogenic epilepsy syndrome; (2) patients with neuropsychiatric comorbidities or dysmorphic features; and (3) patients with undefined phenotypes with multiple candidate genes. Applicable genetic testing methods for epilepsy are as follows: Sanger sequencing, chromosome microarray, targeted gene panels, whole exome sequencing, and whole genome sequencing. Sanger sequencing is indicated for patients with defined phenotypes by a single gene mutation. Chromosome microarray is recommended as part of the initial evaluation of unexplained epilepsy, particularly among patients with associated neuropsychiatric comorbidities or dysmorphic features. Next generation sequencing can be informative in patients with undefined phenotypes with multiple candidate genes. Targeted gene panels are a cost-effective alternative to both Sanger sequencing and whole exome sequencing for the genetic diagnosis of epilepsy. There are, however, social, ethical and even financial hurdles to overcome in the transition of next generation sequencing technology into the clinic. This review focuses on recent transformation of epilepsy genetics and suggests a strategy for actual clinical practice.
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