Epilepsy is a neurological condition characterized by recurrent, unprovoked seizures. These episodes arise from sudden, excessive electrical discharges within brain cells, disrupting normal brain activity. Symptoms can vary widely, ranging from brief lapses in awareness or muscle jerks to more severe, prolonged convulsions. While a single seizure does not indicate epilepsy, a diagnosis is typically made after a person experiences two or more unprovoked seizures occurring at least 24 hours apart.
The Role of Genetics in Epilepsy
The influence of genetics on epilepsy is complex, representing a spectrum rather than a single, simple percentage. Estimates suggest genetics play a role in approximately 30% to 40% of all epilepsies, with some research indicating contributions in up to 70% of cases. Genes can either be the direct cause of epilepsy or create a predisposition, where their presence increases the likelihood of developing the condition, often in combination with other factors. Researchers have identified more than 200 genes linked to various forms of epilepsy, highlighting the broad genetic landscape.
Categories of Genetic Influence
Genetic contributions to epilepsy can be broadly categorized into distinct mechanisms. One category is monogenic epilepsies, resulting from a single gene mutation sufficient to cause the disorder. A well-known example is Dravet syndrome, a severe form of epilepsy that begins in infancy. Over 80% of Dravet syndrome cases are linked to mutations in the SCN1A gene, affecting sodium channels in brain cells.
A second category is polygenic epilepsies, where variations in multiple genes collectively increase susceptibility. Here, no single gene mutation alone causes the condition; instead, combined genetic variations elevate the risk. This pattern is observed in many common forms of genetic generalized epilepsies, such as childhood absence epilepsy and juvenile myoclonic epilepsy.
The third category is multifactorial epilepsies, where genetic predisposition interacts with environmental factors. A person might have a genetic susceptibility that only manifests when triggered by an additional event. Examples include head injuries, certain infections, or maternal smoking during pregnancy. This interaction underscores the complex interplay between genetic makeup and surroundings.
Inheritance Patterns and Family Risk
Even when epilepsy has a genetic basis, its inheritance pattern can vary significantly. Some genetic changes that cause epilepsy are de novo mutations, meaning they occur spontaneously in the affected individual and were not passed down from either parent. These new genetic changes are common in severe early-onset epilepsies and can explain why a person might develop the condition without family history.
For many common forms of epilepsy, the risk to first-degree relatives (e.g., children or siblings) is only slightly increased compared to the general population. While the general population has an epilepsy risk of approximately 0.5% to 1.2%, first-degree relatives of someone with epilepsy may have a risk that is two to ten times higher. The overall risk remains low for most individuals; a child of parents with epilepsy may never develop the condition. Research also suggests the risk might be higher if the affected parent is the mother.
The Purpose of Genetic Testing
Genetic testing for epilepsy can provide valuable information for patients and their families. One primary goal is to identify a specific underlying cause, which can help end a lengthy diagnostic process. Pinpointing a genetic cause can guide the selection of effective anti-seizure medications, representing precision medicine. For example, certain medications, like sodium channel blockers, should be avoided in specific genetic epilepsies (e.g., Dravet syndrome) as they can worsen seizures.
Genetic testing can also offer a more precise prognosis, helping healthcare providers and families understand the likely course of the condition. This information assists in long-term planning and management. Identifying a genetic cause can also inform family planning decisions for those concerned about passing the condition to future children. However, testing does not always reveal a genetic cause and is not necessary for every person with epilepsy.