Seizures are sudden, uncontrolled electrical disturbances in the brain that can be a one-time event or a symptom of the chronic neurological disorder known as epilepsy. The question of whether this condition is passed down through families is complex, as genetics is rarely the only factor involved. For many people, epilepsy results from multiple causes, where a genetic predisposition interacts with other influences to trigger the onset of seizures.
How Genetic Predisposition Works
Genetic predisposition refers to an increased likelihood of developing a disease due to an individual’s genetic makeup. In the context of epilepsy, this often means that a person has inherited a collection of small variations in multiple genes that, when combined, lower their seizure threshold. This is known as polygenic risk, where many genes each contribute a small effect toward increasing vulnerability.
Genes influence the brain by providing instructions for making proteins, especially those that form ion channels on nerve cells, or neurons. These channels regulate the flow of charged particles like sodium and potassium, which are responsible for electrical signaling and excitability. Variations in the genes that encode these channels can lead to an imbalance, causing the brain’s electrical activity to become unstable and prone to uncontrolled firing.
This broad genetic susceptibility must be distinguished from direct inheritance. Even with a genetic predisposition, a person may never develop epilepsy unless additional factors, such as a head injury or illness, trigger the condition. Researchers believe a genetic tendency is present to some extent in nearly all cases of epilepsy, even those caused by acquired brain damage. This underlying tendency may explain why not everyone who experiences a brain injury or infection develops epilepsy.
Specific Genetic Syndromes and Inheritance Patterns
In some cases, the link between genetics and epilepsy is much more direct, involving a variation in a single gene strong enough to cause the disorder on its own. This is known as monogenic inheritance and typically accounts for a small percentage of all epilepsy cases. These clear patterns are more common in early-onset and severe forms, often allowing for a specific diagnosis of an epilepsy syndrome.
Monogenic epilepsies are frequently associated with genes that code for ion channel proteins, which directly control neuronal communication. Dravet Syndrome is an example of a severe monogenic epilepsy involving a variation in the SCN1A gene, which codes for a specific type of sodium channel. Although the condition is described as having an autosomal dominant inheritance pattern, approximately 90% of cases are caused by a de novo mutation.
A de novo mutation means the genetic change arose spontaneously in the child and was not inherited from either parent. Lennox-Gastaut Syndrome (LGS) is another severe epileptic encephalopathy that can be caused by various factors, including genetic changes like CDKL5 or SCN2A. The genetic causes of LGS are usually also the result of spontaneous de novo mutations rather than being passed down from a parent.
The concept of de novo mutation explains why a person may have a severe genetic form of epilepsy without any prior family history. These spontaneous changes occur during the formation of the egg or sperm, or shortly after conception. Identifying these single-gene causes can be useful because it may guide the choice of medication for a more personalized treatment approach.
When Seizures Are Not Hereditary
A significant proportion of epilepsy cases are not primarily caused by inherited or de novo genetic factors. These are known as acquired epilepsies, where the seizures result from a distinct physical cause that damages the brain. In about half of all cases, a specific cause cannot be identified, but many known causes are non-genetic.
Acquired epilepsies result from structural or functional damage that makes the brain tissue susceptible to abnormal electrical activity.
Common Acquired Causes
Common non-genetic causes of epilepsy include:
- Traumatic brain injury (TBI) from accidents.
- Stroke or interrupted blood flow.
- Brain infections such as meningitis or encephalitis.
- Brain tumors or malformations of brain development.
- Complications from cerebral hypoxia (oxygen deprivation).
- Metabolic disorders that affect how the body processes energy or essential nutrients.
- Autoimmune conditions where the immune system mistakenly attacks brain cells.
Understanding Your Risk and Genetic Counseling
Understanding the risk of passing on epilepsy is a natural concern for individuals with the disorder or a family history. The overall risk for a child in the general population to develop epilepsy by age 20 is approximately 1%. This risk increases slightly for children whose parents have epilepsy, generally falling into the range of 2% to 5%.
The specific type of epilepsy a parent has greatly influences the risk to their children. For example, the risk is much higher for developing generalized epilepsy if the parent has generalized epilepsy, but only slightly increased for focal epilepsy. Having a first-degree relative with inherited epilepsy can increase an individual’s risk by two to four times compared to the general population.
Consulting with a genetic counselor provides a personalized risk assessment based on the specific type of epilepsy, family history, and testing results. Genetic counselors specialize in interpreting complex genetic information and discussing the implications for the patient and their family members. They help determine if multi-gene panel testing or broader whole exome sequencing is appropriate.
Testing is often recommended for individuals with unexplained epilepsy, as identifying a genetic cause can confirm a diagnosis or predict potential severity. A clear genetic diagnosis provides an explanation for the condition, which is helpful for families where the cause was previously unknown. Counseling ensures that the benefits and limitations of testing are fully understood before proceeding.