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Your genes provide the instruction booklet for making proteins for your cells. Even the smallest changes in your DNA can have a major impact on your health. Mutations (changes) in the SCN1A gene can cause Dravet syndrome and lead to childhood epilepsy. Most gene changes develop randomly, but a few are passed down through families.
This article will explore SCN1A mutations and how they play a role in Dravet syndrome. We’ll also discuss other genetic changes seen in Dravet syndrome and related conditions. To learn more about SCN1A and genetic testing for your family’s situation, talk to a genetic counselor.
SCN1A mutations are present in around 80 percent of Dravet syndrome cases. The SCN1A gene provides the instructions for making sodium channels. These pores let sodium in and out of cells. Sodium channels help cells create and send electrical signals to one another. Neurons (brain cells) communicate with one another using these electrical signals.
In people with Dravet syndrome, half of the sodium channels in cells don’t work like they should. Some people may not even make the channels at all. Problems with these sodium channels lead to seizures and other symptoms of Dravet syndrome.
Researchers have found over 6,000 spots on the SCN1A gene for mutations. People can have changes in different places on the gene, which results in different Dravet syndrome symptoms. Even if doctors know the exact SCN1A mutation a person has, they can’t predict how severe their condition will be. It’s also impossible to determine how they’ll be affected long-term.
Studies show that some people with Dravet syndrome develop extra copies of the SCN1A gene. This is known as a copy number variation. Others may have pieces of DNA missing (called deletions) or rearranged. All of these genetic changes affect how well the SCN1A gene works. Without the correct instructions, cells can’t make the right proteins.
It’s also important to note that not all SCN1A mutations cause Dravet syndrome. Some people with these genetic changes instead experience other seizure disorders or migraines. Dravet syndrome is a severe form of genetic epilepsy related to SCN1A changes.
Dravet syndrome is a rare form of epilepsy (developmental and epileptic encephalopathies) that starts within the first year of life. It was previously known as severe myoclonic epilepsy of infancy (SMEI). Dravet syndrome is both severe and often resistant to anti-seizure medications.
Dravet syndrome is one of many seizure disorders associated with SCN1A gene mutations. Compared to the other disorders, Dravet syndrome tends to have worse outcomes. Examples of other seizure problems seen with SCN1A mutations include:
SCN1A mutations are the most common causes of Dravet syndrome. However, researchers have found other genetic changes associated with this condition. These other mutations are seen in between 10 percent to 15 percent of Dravet syndrome cases. Examples include SCN1B, SCN2A, and GABRG2.
Studies have found people with SCN1B mutations can also develop GEFS or Dravet syndrome. The signs and symptoms look very similar to the ones seen with SCN1A mutations. Examples include seizures that can’t be managed with medications and intellectual disability. Children with SCN1A and SCN1B mutations both develop symptoms early in childhood.
SCN2A mutations don’t directly cause Dravet syndrome — but they can lead to the development of similar conditions. Other related intellectual and seizure disorders include:
People with SCN1A mutations typically don’t respond well to medications that block sodium channels and their symptoms may even worsen with these medications. On the other hand, these treatments tend to work better for seizures in those with SCN2A changes.
The GABRG2 gene provides instructions to make proteins that help neurons talk to one another. Like SCN1A, GABRG2 also makes ion channels that send electrical signals. Mutations in the gene affect how well the channels work — making them overactive or underactive. Changes in the GABRG2 gene are usually de novo and happen randomly, rather than being inherited. However, in rare cases, they may be passed down through families.
Children with GABRG2 mutations can develop severe seizure disorders, including Dravet syndrome. In these cases, children may have other complications like:
In nearly all cases, the changes in SCN1A are de novo mutations. This means they happen randomly without any family history. Studies estimate that only 4 percent to 10 percent of SCN1A mutations are passed down through family members.
Most people inherit two copies of every gene — one from their mother and one from their father. If you inherit an SCN1A mutation, you have a 50 percent chance of passing it down to your children. This also means there’s a 50 percent chance it doesn’t get passed down. Remember, not everyone with a SCN1A mutation will develop Dravet syndrome.
SCN1A mutations in Dravet syndrome are known as autosomal-dominant mutations. Dominant mutations only need to affect one gene copy to cause a disorder. It’s much less common for Dravet syndrome to be autosomal recessive — meaning you need two faulty gene copies to have a disorder.
If your child has Dravet syndrome, you may wonder if you carry an SCN1A mutation. Some parents carry SCN1A mutations — but they don’t have Dravet syndrome like their child. Many factors play a role in how a person’s genotype (DNA) affects the phenotype (physical symptoms).
For example, a parent with an SCN1A mutation may have other genes that compensate for the change. These changes may not be passed down to their child who develops Dravet syndrome. Your environment also influences your chances of having a disease. Researchers think that stress early in life and certain medications may play a role in Dravet syndrome development. However, most of the risk is due to genetics and how the body functions, while environmental factors likely play a smaller and less well-understood role.
Read about dental issues that may develop with Dravet syndrome.
If your child has received a Dravet syndrome diagnosis, you may be interested in genetic testing for yourself. There’s a small chance your child has inherited an SCN1A mutation from you. Families with a history of seizures or epilepsy may benefit from working with a genetic counselor.
Genetic counselors are specialists trained to support families with genetic diseases — like Dravet syndrome. They can recommend testing and help you understand the next steps of living with genetic conditions. Genetic counselors provide education on the chances of passing down a genetic condition and what the risks are.
Treating epilepsy syndromes like Dravet syndrome requires a team of healthcare professionals. A genetic counselor can connect you to other resources. A specialist — like a neurologist — will need to make a clinical diagnosis of Dravet syndrome based on signs and symptoms. Together, your healthcare team will help guide testing, diagnosis, and treatment.
Read about Lennox-Gastaut syndrome, another severe form of epilepsy related to genetic changes.
On MyEpilepsyTeam, people share their experiences with epilepsy, get advice, and find support from others who understand.
Have you or your child had genetic testing for Dravet syndrome with SCN1A mutations? Let others know in the comments below.
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