SCN1A-Related Epilepsies

SCN1A (sodium voltage-gated channel alpha subunit 1) is a gene that provides instructions for making one part of a sodium channel called NaV1.1. These channels control the flow of sodium into cells in the brain (neurons), which is necessary for electrical balance. Many different DNA variants have been identified in the SCN1A gene, but a specific variant does not always predict the severity of epilepsy. There is still much that is unknown about SCN1A variant types and how they may contribute to specific outcomes within each seizure disorder classification.

In most cases, including in Dravet syndrome, the variants are “loss of function,” which means that the variant leads to a non-functional sodium channel in cells called interneurons.

Interneurons normally suppress brain cells from generating electrical activity, but in the presence of the SCN1A variant, they are no longer able to adequately suppress electrical activity, leading to a predisposition to seizures. Less commonly, SCN1A variants are “gain-of-function” and affect brain cells directly, leading to excessive electrical activity and seizures.

SCN1A variants that result in severe epilepsies, like Dravet syndrome, usually occur de novo, meaning that the variant was not inherited but occurred for the first time in the person with epilepsy. There are exceptions to this, however, as some individuals with Dravet syndrome have family members with the same SCN1A variant who are much more mildly impacted or have no history of epilepsy. SCN1A variants that lead to less severe epilepsies are often inherited from a parent. Genetic counseling is recommended for the families of all individuals who have SCN1A variants.