When a child has a seizure, many parents assume that anticonvulsants should be used. However, these medications are not suitable for everyone. There are many types of inherited epilepsies that make up a significant proportion of pediatric epilepsy. In Dravet syndrome, for example, standard anticonvulsants may do more harm than good.

“Regardless of the specific genetic mutation, conventional anticonvulsant drugs may help in some cases of hereditary epilepsy but may worsen the condition in others,” said Professor Lim Byung-chan of the Department of Pediatrics at Seoul National University Hospital in an online class at the SNUH Rare Disease Center.

According to Professor Lim, sodium channel blockers, which are conventional anticonvulsants, are not recommended for Dravet syndrome, commonly caused by genetic mutations affecting sodium channels, one of the key mechanisms underlying hereditary epilepsy. However, there are some inherited epilepsies where sodium channel blockers are helpful. Inherited epilepsies caused by abnormalities in the PRRT2, KCNQ2, and SLC2A genes are helped by sodium channel blockers.

Also, because all of the hereditary epilepsies classified as rare are different from one another, the treatments available vary. So, what may not work for another child may work for yours. For example, abnormalities in the KCNT1 gene may benefit from antiarrhythmic medications. For hereditary epilepsy caused by abnormalities in the SLC2A1 gene, a ketogenic diet is known to be beneficial.

"Because many arrhythmia medications work on ion channels in the heart, they may also work on ion channels in the brain. In some cases, there are epilepsy conditions that benefit from a ketogenic diet,” Lim said. "The caveat is that this shouldn't be exaggerated. It's a tiny percentage of all epilepsy."

Hereditary epilepsy is not easy to diagnose. There are many genes involved in hereditary epilepsy, and the number is skyrocketing every year. More often than not, the genetic abnormality starts in the patient's family rather than in the parents. So, how many children are affected by hereditary epilepsy?

According to international data, 47.2 children per 100,000 population are affected by a single-gene disorder, with onset before the age of three. In terms of frequency by gene, PRRT2 gene abnormalities occur in 10.0 per 100,000 people, SCN1A gene abnormalities in 8.2 per 100,000 people, KCNQ2 gene abnormalities in 5.8 per 100,000 people, and SLC2A1 gene abnormalities in 4.1 per 100,000 people.

“I don't think there's a racial disparity (in pediatric hereditary epilepsy),” Lim said. While the population of pediatric hereditary epilepsy is not small, each of the causative genes is a rare disease. “Each individual inherited epilepsy, no matter how common and how often it occurs, falls into the category of rare,” he added.

Inherited epilepsy is not always easy to diagnose, even for healthcare providers. Because genetic abnormalities can occur at the gene level or at the chromosomal level (where genes are clustered together), genetic testing and chromosomal testing are used to identify problems at both the gene and chromosomal levels. However, these two tests are not enough to find all the genes responsible.

"If a hereditary cause is not found, it may not be hereditary epilepsy, but it may not have been found because the necessary range of tests was not done," Professor Lim said. “Also, as the scope of testing has expanded, the test results may not point to a single cause, but rather list multiple candidates, so it depends on the medical center to determine which one is the cause."

This can lead to a false diagnosis of no cause when there is a genuine genetic cause of epilepsy.

"They may say it (hereditary epilepsy) is a cause when it's not," Lim said. “We have to be very careful because we can say that there is no cause when there is a clear cause."

In some cases, it is very difficult to interpret, Lim said, pointing to the limitations of the current diagnosis of epilepsy.