Genetics and Partial Onset Seizures: What You Need to Know
Oct, 13 2025
Seizure Treatment Guide
How Your Genes Guide Treatment
This interactive tool helps you understand how specific gene variants affect treatment options for focal seizures. Select your gene variant to see recommended medications and those to avoid.
Select a gene variant and seizure type to see personalized treatment recommendations.
Key Takeaways
- Partial onset seizures start in one brain area and can be shaped by specific gene variants.
- SCN1A, KCNQ2 and PRRT2 are the three most frequently implicated genes.
- Genetic testing helps pinpoint cause, guide medication choices, and inform family planning.
- Inheritance patterns are usually autosomal dominant with variable expressivity.
- Combining EEG findings with genetic results gives the most accurate diagnosis.
Understanding Partial Onset Seizures
When discussing partial onset seizures (also called focal seizures) they begin in a specific region of the brain and may stay confined or spread to other areas, the clinical picture can be remarkably diverse. Some people experience a brief staring spell, while others have jerking movements of a single limb or a sudden wave of fear. Because the electrical storm originates locally, the symptoms reflect the function of that brain zone - a seizure in the temporal lobe may produce déjà vu, whereas a frontal‑lobe event often causes motor jerks.
The term "partial" is now officially replaced by "focal" in the International League Against Epilepsy (ILAE) terminology, but many clinicians and patients still use the older phrase. Recognizing that focal seizures can arise from structural lesions, infections, metabolic disturbances, or genetics is the first step toward tailored care.
How Genetics Shapes Partial Onset Seizures
Research over the past two decades has shown that genetics is the study of inherited DNA variations that can predispose individuals to neurological disorders plays a central role in a subset of focal seizures. While not every case has a detectable genetic cause, about 10‑15% of patients with unexplained focal epilepsy carry pathogenic variants in known epilepsy genes.
The underlying mechanism often involves ion‑channel dysfunction. When a gene that codes for a sodium, potassium, or calcium channel mutates, the neurons become either hyper‑excitable or fail to fire properly, creating the perfect storm for a seizure focus.
Understanding the genetics of partial onset seizures helps clinicians move beyond a "one‑size‑fits‑all" approach. It opens doors to precision medicine-selecting antiepileptic drugs (AEDs) that target the specific channel defect, avoiding medications that could worsen the condition.
Key Genes Linked to Focal Seizures
Below are the three genes most commonly associated with focal epilepsy. Each has distinct inheritance patterns, typical seizure phenotypes, and treatment considerations.
| Gene | Inheritance | Typical Focal Seizure Type | Treatment Tips |
|---|---|---|---|
| SCN1A encodes the Nav1.1 sodium channel alpha subunit | Autosomal dominant (often de novo) | Temporal‑lobe or multifocal seizures, sometimes with fever‑sensitivity | Avoid sodium‑channel blockers like carbamazepine; consider valproate or levetiracetam |
| KCNQ2 codes for a potassium channel subunit (Kv7.2) | Autosomal dominant with variable expressivity | Focal motor seizures, often beginning in infancy | Retigabine (ezogabine) targets KCNQ channels; otherwise use broad‑spectrum AEDs |
| PRRT2 involved in synaptic vesicle release | Autosomal dominant, high penetrance | Paroxysmal kinesigenic dyskinesia and brief focal seizures | Low‑dose carbamazepine often highly effective |
Genetic Testing: When and How
Genetic testing is not a blanket recommendation for every epilepsy patient. Ideal candidates include:
- Individuals with focal seizures of unknown cause after MRI and metabolic workup.
- Patients with a family history of epilepsy or early‑onset seizures.
- Children whose seizures are refractory to two or more AEDs.
Testing options range from targeted gene panels (covering the most common epilepsy genes) to whole‑exome sequencing (WES) and, in rare cases, whole‑genome sequencing (WGS). Panels are faster and cheaper, while WES increases the chance of discovering novel variants.
Before ordering a test, clinicians typically discuss the process with a genetic counselor. This ensures patients understand possible outcomes-positive, negative, or variants of uncertain significance (VUS)-and the implications for insurance, family planning, and psychosocial wellbeing.
Results are interpreted in light of the EEG recording of brain electrical activity used to locate seizure focus pattern, MRI findings, and clinical history. A pathogenic SCN1A variant combined with a focal temporal‑lobe spike‑and‑slow‑wave pattern, for example, strongly points toward a genetic etiology.
Impact on Treatment Choices
Knowing the exact genetic driver can shift the therapeutic strategy dramatically. Here are three practical ways genetics informs medication selection:
- Channel‑specific drugs: Retigabine enhances KCNQ2‑mediated potassium currents, making it a logical choice for KCNQ2‑related seizures.
- Avoidance of contraindicated AEDs: Sodium‑channel blockers such as carbamazepine can exacerbate seizures in SCN1A mutation carriers.
- Precision diet therapy: Some focal epilepsy patients with GLUT1 deficiency respond to a ketogenic diet, though this is a metabolic rather than pure genetic cause, it illustrates the broader principle of genotype‑guided interventions.
Beyond medication, genetic insight can guide surgical decisions. If a pathogenic variant is discovered but the EEG shows a well‑localized, drug‑resistant focus, resective surgery may still be an option, but the risk‑benefit analysis will weigh the likelihood of cure against the possibility of widespread network involvement due to the genetic defect.
Family Planning and Inheritance
Most focal epilepsy genes follow an inheritance pattern describes how a genetic trait is transmitted across generations, often autosomal dominant for epilepsy genes. This means a child has a 50% chance of inheriting the variant if one parent carries it.
However, penetrance is variable-some carriers never develop seizures, while others have severe epilepsy. This uncertainty makes pre‑conception counseling essential. Options include:
- Pre‑implantation genetic diagnosis (PGD) with IVF to select embryos without the pathogenic variant.
- Prenatal testing (amniocentesis or chorionic villus sampling) when pregnancy occurs naturally.
- Accepting the risk and preparing for early monitoring and possible early intervention.
It’s also worth noting that de novo mutations-new changes not present in either parent-account for a sizable portion of SCN1A cases. In those situations, recurrence risk for future siblings is low, but the affected individual still faces a 50% transmission risk to their own children.
Common Misconceptions
Many patients assume that "genetic" automatically means "untreatable." The reality is far more nuanced. While a genetic diagnosis can reveal why certain drugs failed, it also opens doors to targeted therapies that may not have been tried otherwise.
Another frequent myth is that only severe epilepsies are genetic. In fact, even mild, infrequent focal seizures can have an underlying genetic cause. Conversely, not every focal seizure has a genetic origin; structural lesions, trauma, or infections remain common culprits.
Next Steps and Resources
If you suspect a genetic component to your focal seizures, consider these actions:
- Schedule an appointment with a neurologist who specializes in epilepsy genetics.
- Request a referral to a certified genetic counselor.
- Gather any family medical history, especially relatives with seizures, developmental delays, or unexplained neurological issues.
- Maintain a seizure diary to help correlate triggers, EEG findings, and potential genotype‑phenotype patterns.
Useful organizations include the Epilepsy Foundation, the International League Against Epilepsy, and the Genetics Society of Australia. Many of them offer patient-friendly guides on genetic testing and support groups for families navigating an epilepsy diagnosis.
Frequently Asked Questions
Can I get a genetic test if I already have an MRI?
Yes. Even when MRI shows no structural abnormality, a genetic test can uncover hidden causes. In many clinics the MRI and genetic work‑up are ordered together for a comprehensive evaluation.
Will a positive genetic result change my medication?
Often it does. For instance, a confirmed SCN1A mutation advises against sodium‑channel blockers, while a KCNQ2 variant suggests trying potassium‑channel openers if they’re available.
Is genetic testing covered by insurance in Australia?
Many private health funds cover targeted epilepsy panels when a neurologist recommends them. Public Medicare may fund tests if the case meets specific clinical criteria, such as drug‑resistant epilepsy with no identifiable cause.
What if my test returns a variant of uncertain significance?
A VUS means the lab cannot yet decide if the change is harmful. Your doctor may monitor your seizure pattern closely, repeat testing later, or look for additional evidence from family members.
Can lifestyle changes affect genetically‑driven focal seizures?
Yes. Adequate sleep, stress management, and avoiding known triggers (like flashing lights for some photic‑sensitive individuals) can reduce seizure frequency, even when a genetic mutation is present.
