Dravet syndrome is caused by a mutation in the SCN1A gene in 80 to 90 percent of cases. This gene provides instructions for building a specific sodium channel in the brain, and when it’s faulty, the brain loses a critical braking system that normally prevents excessive electrical activity. The result is severe, treatment-resistant epilepsy that typically begins in the first year of life, with seizures often triggered by fever or elevated body temperature.
The SCN1A Gene and How It Causes Seizures
To understand what goes wrong in Dravet syndrome, it helps to know how the brain keeps itself in balance. Your brain has two opposing forces at work: excitatory neurons that fire signals and inhibitory neurons that quiet things down. Inhibitory neurons act like brakes, preventing runaway electrical activity. The SCN1A gene builds a sodium channel called Nav1.1, which is essential for those inhibitory neurons to fire properly.
Nav1.1 channels sit primarily at the starting point of inhibitory neurons called parvalbumin-positive interneurons. These channels let sodium rush into the cell, generating the electrical impulse the neuron needs to do its job. When SCN1A is mutated, the channel either doesn’t work correctly or isn’t produced in sufficient quantities. The inhibitory neurons can’t fire fast enough or strongly enough, which means less of the calming neurotransmitter GABA gets released into surrounding brain tissue.
The consequences cascade from there. With weakened inhibition, excitatory neurons go unchecked. The brain’s excitation-inhibition balance tips toward hyperexcitability, and seizures follow. About 80% of SCN1A missense mutations (where a single building block of the gene is swapped) specifically disrupt the channel’s ability to open and close in response to voltage changes, selectively crippling the inhibitory side of the equation while leaving excitatory neurons largely unaffected.
This isn’t just a seizure problem. The same inhibitory circuits play roles in cognitive development, motor coordination, and behavior. When these circuits malfunction from early infancy, the developmental consequences compound over time, which is why Dravet syndrome is classified as an epileptic neurodevelopmental disorder rather than epilepsy alone.
Most Cases Arise From New Mutations
In most children with Dravet syndrome, the SCN1A mutation occurred spontaneously during early embryonic development or in the egg or sperm cell that formed the embryo. It was not inherited from either parent. Geneticists call these “de novo” mutations, and they explain why Dravet syndrome so often appears in families with no history of epilepsy.
In a smaller number of cases, a parent carries the mutation in only some of their cells, a phenomenon called somatic mosaicism. A mosaic parent might have mild or no symptoms because only a fraction of their brain cells carry the faulty gene. Their child, however, can inherit the mutation in every cell and develop the full syndrome. Researchers have documented mosaic parents with SCN1A variants present in roughly 18 to 31 percent of their blood cells who experienced only febrile seizures in childhood, while their children who carried the mutation in all cells had classic Dravet syndrome.
The severity differences tied to mosaicism likely depend on how many cells in disease-relevant brain regions carry the mutation. Two people with the exact same SCN1A variant can have dramatically different outcomes if one is mosaic and the other is not. In rare cases, a parent with a seizure history passes the mutation on through standard inheritance, but this is uncommon.
Other Genes Linked to Dravet Syndrome
The remaining 10 to 20 percent of Dravet syndrome cases that don’t involve SCN1A have been linked to mutations in over a dozen other genes. These include PCDH19, SCN2A, SCN8A, SCN1B, GABRA1, GABRG2, GABRB3, HCN1, STXBP1, CHD2, CPLX1, and KCNA2. Many of these genes also play roles in either sodium channel function or inhibitory neurotransmission, so they disrupt the same fundamental balance between excitation and inhibition, just through different molecular pathways.
For some of these genes, evidence is still limited. Only single case studies have been reported for CHD2, CPLX1, HCN1, and KCNA2. Others, like PCDH19 and SCN2A, have been documented more frequently and may produce a clinical picture that overlaps heavily with Dravet syndrome without being identical. Clinicians sometimes refer to these as “Dravet syndrome-like phenotypes” to acknowledge the similarity while recognizing a distinct genetic cause.
Why Fever and Heat Trigger Seizures
One of the hallmark features of Dravet syndrome is extreme sensitivity to elevated body temperature. Seizures are frequently triggered by fever, hot baths, warm weather, physical exertion, or illness. This sensitivity is directly tied to the underlying sodium channel dysfunction.
In a healthy brain, inhibitory neurons can keep pace with the increased excitability that comes with rising body temperature. In a brain with reduced Nav1.1 function, those inhibitory neurons are already struggling. When temperature goes up, the threshold for triggering an action potential in inhibitory neurons climbs even higher, making it harder for them to fire. Meanwhile, excitatory neurons become more active with heat. The gap between excitation and inhibition widens, and seizures break through.
Research in mouse models carrying Nav1.1 mutations confirms this mechanism: haploinsufficiency (having only one working copy of the gene) in parvalbumin-positive interneurons increases the threshold for action potential generation and impairs the ability to fire repeatedly, making thermally induced seizures far more likely. This is why the first seizure in Dravet syndrome often happens between 3 and 9 months of age, with a median onset around 6 months, frequently in the context of a fever, illness, or routine immunization that raises body temperature.
How Dravet Syndrome Gets Diagnosed
Diagnosis typically begins when an otherwise healthy infant has a prolonged or unusual seizure with fever. What distinguishes Dravet syndrome from simple febrile seizures is what happens next: further convulsive seizures occur, often with fever, sometimes affecting only one side of the body, and often lasting longer than typical febrile seizures. According to the International League Against Epilepsy, this pattern of recurrent convulsive seizures, especially if they are one-sided or prolonged, supports the diagnosis. Confirmation comes from genetic testing that identifies a pathogenic SCN1A variant.
A population-based study in Sweden found that the cumulative incidence of Dravet syndrome is roughly 1 in 33,000 live births for children born between 2010 and 2018, up from about 1 in 46,000 for children born the prior decade. The increase likely reflects better awareness and earlier genetic testing rather than a true rise in cases. The median age at diagnosis dropped from 4.5 years to 1.6 years over that same period, meaning children are being identified much sooner than they were a generation ago.
In settings where genetic testing isn’t available, the ILAE notes that Dravet syndrome can still be diagnosed based on clinical criteria alone, provided the seizure pattern and developmental trajectory fit and no features suggest an alternative condition.