EPILEPSY — GENETIC TESTING

Epilepsy Genetic Testing — where the specific gene determines which anti-seizure medication works, which one makes seizures worse, and whether precision therapies like the ketogenic diet or mTOR inhibitors are indicated.

Whole genome sequencing evaluates all 100+ epilepsy genes simultaneously — SCN1A, SCN2A, KCNQ2, CDKL5, STXBP1, SLC2A1, TSC1/TSC2, and others — providing the molecular diagnosis that guides gene-specific treatment selection.

SCN1A
SCN2A
KCNQ2
CDKL5
STXBP1
SLC2A1
TSC1
TSC2

About this condition

Epilepsy — Genetic Testing

Epilepsy affects approximately 1 in 26 people (3.4 million in the US), and up to 70-80% of cases have a genetic etiology — from single-gene (monogenic) epilepsies to complex polygenic susceptibility. Over 100 monogenic epilepsy genes have been identified, encoding ion channels (SCN1A, SCN2A, KCNQ2, KCNQ3, KCNA2), synaptic proteins (STXBP1, SYNGAP1), metabolic enzymes (SLC2A1, ALDH7A1), transcription factors (CDKL5, FOXG1), and mTOR pathway components (TSC1, TSC2, DEPDC5). Genetic diagnosis is increasingly guiding treatment selection.

Gene-specific treatment is the most important application of epilepsy genetics. SCN1A variants (Dravet syndrome) — patients are worsened by sodium channel blockers (carbamazepine, phenytoin, lamotrigine), the most commonly prescribed anti-seizure class. KCNQ2 variants — respond to sodium channel blockers, particularly carbamazepine. SLC2A1 variants (GLUT1 deficiency) — the ketogenic diet is the treatment of choice, and anti-seizure medications alone are insufficient. TSC1/TSC2 variants — everolimus (mTOR inhibitor) is FDA-approved for TSC-associated seizures. These gene-specific treatment responses mean that empirical anti-seizure medication selection without genetic diagnosis risks using the wrong drug.

Approximately 30% of epilepsy patients are refractory to standard anti-seizure medications (drug-resistant epilepsy). Genetic testing in refractory epilepsy identifies the cause in approximately 20-40% of cases — often revealing that drug resistance was actually drug-inappropriateness (wrong medication for the genetic subtype). Additionally, genetic diagnosis of epilepsy informs surgical candidacy, developmental prognosis, recurrence risk counseling, and eligibility for gene-specific clinical trials (ASOs for SCN1A, gene therapy for CDKL5 and STXBP1).

SCN1A patients are WORSENED by sodium channel blockers — the most commonly prescribed anti-seizure class. This is among the most important pharmacogenomic interactions in neurology. Molecular SCN1A diagnosis prevents iatrogenic seizure worsening.

Gene locus: SCN1A (2q24.3), SCN2A (2q24.3), KCNQ2 (20q13.33), CDKL5 (Xp22.13), STXBP1 (9q34.11), SLC2A1 (1p34.2), TSC1 (9q34.13), TSC2 (16p13.3)

100+ epilepsy genes cannot be tested sequentially. The specific gene determines the right medication, the wrong medication, and whether precision therapies (ketogenic diet, mTOR inhibitors, ASOs) are indicated.

30% of 'drug-resistant' epilepsy may actually be 'wrong-drug' epilepsy — genetic diagnosis identifies the correct treatment

A patient with SCN1A-related Dravet syndrome prescribed carbamazepine (a first-line anti-seizure medication) will experience worsened seizures — and may be labeled 'drug-resistant' rather than 'inappropriately treated.' Genetic diagnosis reveals that the seizures are not refractory to all medications — just to sodium channel blockers. Switching to clobazam, stiripentol, or fenfluramine (all effective in SCN1A) may dramatically improve seizure control. WGS identifies the specific gene, enabling selection of the optimal medication from the outset.

Gene therapy trials for CDKL5, STXBP1, SCN1A in development — molecular diagnosis determines eligibility

ASO therapies for SCN1A (targeting gain-of-function variants), gene replacement therapy for CDKL5 deficiency disorder, and multiple additional gene-specific approaches are in preclinical and early clinical development. All trials require confirmed molecular diagnosis of the specific causative gene. Early genetic diagnosis ensures that patients are identified and enrolled in trials when they become available — before years of uncontrolled seizures cause cumulative developmental harm.

Epilepsy Genetic Testing — where the specific gene determines which anti-seizure medication works, which one makes seizures worse, and whether precision therapies like the ketogenic diet or mTOR inhibitors are indicated.

Epilepsy — Genetic Testing

100+ epilepsy genes cannot be tested sequentially. The specific gene determines the right medication, the wrong medication, and whether precision therapies (ketogenic diet, mTOR inhibitors, ASOs) are indicated.

30% of 'drug-resistant' epilepsy may actually be 'wrong-drug' epilepsy — genetic diagnosis identifies the correct treatment

Gene therapy trials for CDKL5, STXBP1, SCN1A in development — molecular diagnosis determines eligibility

Others in Neurological

One test. A lifetime of answers.