Dravet syndrome causes
Fact-checked by Dravet syndrome, a rare and severe genetic epilepsy, is usually caused by mutations in the SCN1AÂ gene, although other types of genetic mutations may rarely be involved.
These mutations are thought to disrupt normal nerve communication patterns in the brain to cause disease symptoms, including prolonged seizures that often start in the first year of life.
Numerous triggers, such as fevers or infections, can bring on seizures in people with Dravet syndrome, although these vary between individuals and often change with age.
Knowing the underlying cause of Dravet and seizure triggers for each individual can help guide treatment and management strategies for people living with Dravet syndrome.
SCN1A mutations
SCN1A gene mutations account for the vast majority of cases of Dravet syndrome. These mutations disrupt typical brain signaling, leading to surges of uncontrolled nerve cell (neuron) activity — the defining feature of a seizure.
How do SCN1A mutations cause seizures in Dravet syndrome?
Communication in the brain requires excitatory signals, which activate neurons, and inhibitory signals, which act like brakes that suppress neuron activity. For the brain to function properly, these opposing signals must stay in balance. A seizure occurs when the balance becomes disrupted, and too many neurons start firing simultaneously.
The link between SCN1A mutations and seizures is related to this type of disruption. The gene contains instructions for cells to manufacture a part of the sodium channel NaV1.1. This channel controls the flow of sodium into nerve cells, particularly inhibitory neurons, which dictates when they’ll fire an electrical signal.
Dravet-causing mutations result in a lack of functional NaV1.1 channels, so inhibitory neurons don’t always send the signals they should. Consequently, excitatory signals take over, triggering seizures and other symptoms.
Other cellular processes may contribute to Dravet symptoms, although these are not fully understood.
Types of SCN1A mutations
Many different SCN1A mutations, or gene variants, can lead to Dravet syndrome. There may be a relationship between different variants and disease symptoms or severity, but scientists don’t fully understand this potential link.
Most of the time, Dravet syndrome is not a hereditary form of epilepsy. Around 90% or more of Dravet-causing SCN1A mutations are de novo mutations, meaning they arise spontaneously before birth and do not run in the family. In the remaining 5% to 10% of cases, the disease is caused by genetic mutations inherited from a biological parent.
Every person has two copies of SCN1A, and only one of them needs to have a mutation for Dravet to develop. A person with Dravet has about a 50% chance of passing the disease-causing mutation on to any of their biological children.
However, not all SCN1A mutations cause Dravet syndrome in children. Various mutations can cause other forms of pediatric epilepsy or non-epileptic conditions.
Other genes linked to Dravet syndrome
Although SCN1A mutations are the most common genetic causes of Dravet syndrome, other genetic mutations may also cause the disease or similar symptoms. Some of these genes are involved in inhibitory neuron function, like SCN1A, or regulate brain signaling in other ways.
Mutations in GABRG2, GABRA1, or SCN1B are among the other possible causes of Dravet syndrome. Other genes that were previously linked to Dravet may now be associated with different diagnoses.
Genetic testing for Dravet syndrome can identify mutations in SCN1A or other epilepsy-related genes. Although confirmation of a genetic mutation isn’t, in itself, sufficient to diagnose Dravet syndrome, it is often an important part of the diagnostic process.
Even in people with SCN1A mutations, other genes may contribute to how the disease presents and develops.
Seizure triggers
Seizure triggers — events that can bring on seizures in people who have Dravet syndrome but aren’t the underlying cause of the disease — vary between individuals and may change over time. Common seizure triggers in Dravet syndrome include:
- fevers
- infections
- cold or warm temperatures
- bright or flickering lights
- physical activity
- tiredness
- sleeping
- strong emotions
- noise
Identifying triggers can help patients and caregivers avoid situations that might cause seizures whenever possible.
The mild fevers that sometimes develop after vaccination may trigger seizures in children with Dravet syndrome, which is why the first symptoms sometimes emerge after a newborn’s initial round of vaccines. However, this is not the cause of the disease, and experts still recommend vaccines for most children.
How the cause affects diagnosis and treatment
Genetic testing can help establish an accurate, early diagnosis when Dravet syndrome is suspected. An identified SCN1A mutation, along with clinical signs of the disease, will enable doctors to distinguish Dravet from other types of pediatric epilepsy.
Knowing the cause of a child’s seizures is also critical for making appropriate treatment decisions. Certain medications commonly used for seizure management in other forms of epilepsy need to be avoided by most people with Dravet because they can make seizures worse.
In the future, targeted gene therapies might help treat the root causes of Dravet syndrome for people with certain mutations, but these remain experimental.
Dravet Syndrome News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
