Dravet syndrome is an epilepsy syndrome that begins in infancy or early childhood and can include a spectrum of symptoms ranging from mild to severe.

Children with Dravet syndrome initially show focal (confined to one area) or generalized (throughout the brain) convulsive seizures that start before 15 months of age (often before age one). These initial seizures are often prolonged and involve half of the body and may be followed by seizures that switch to the other side of the body. Other seizure types emerge after 12 months of age and can be quite varied. Status epilepticus—a state of continuous seizure requiring emergency medical care—may occur frequently, particularly in the first five years of life.

Children with the disorder typically have normal development in the first few years of life. As seizures increase, the pace of acquiring skills slows and children start to lag in development behind their peers. Other symptoms can begin throughout childhood with changes in eating, appetite, balance, and a crouched gait (walking).

Most cases of Dravet syndrome are caused by mutation in the SCN1A gene, which is required for the proper function of brain cells. Dravet syndrome is a lifelong condition.

Seizures in Dravet syndrome are difficult to control but can be reduced by anticonvulsant drugs. Some anticonvulsant medications (such as oxcarbazepine, carbamazepine, phenytoin, and lamotrigine) should not be used on a daily basis as they may make seizures worse. A ketogenic diet, high in fats and low in carbohydrates, also may be helpful.

The U.S. Food and Drug Administration (FDA) approved the drugs fenfluramine and cannabidiol to treat seizures with Dravet syndrome in people ages 2 and older.

Normal Function

The SCN1A gene belongs to a family of genes that provide instructions for making sodium channels. These channels, which transport positively charged sodium atoms (sodium ions) into cells, play a key role in a cell's ability to generate and transmit electrical signals.

The SCN1A gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.1. These channels are primarily found in the brain, where they control the flow of sodium ions into cells. NaV1.1 channels are involved in transmitting signals from one nerve cell (neuron) to another. Communication between neurons depends on chemicals called neurotransmitters, which are released from one neuron and taken up by neighboring neurons. The flow of sodium ions through NaV1.1 channels helps determine when neurotransmitters will be released.

Health Conditions Related to Genetic Changes

Familial hemiplegic migraine

At least seven mutations in the SCN1A gene have been identified in people with familial hemiplegic migraine type 3 (FHM3), a form of migraine headache that runs in families. Each of these mutations changes a single protein building block (amino acid) in the NaV1.1 channel, which alters the channel's structure. The abnormal channels stay open longer than usual, which increases the flow of sodium ions into neurons. This increase triggers the cell to release more neurotransmitters. The resulting changes in signaling between neurons make people with FHM3 more susceptible to developing these severe headaches.

Genetic epilepsy with febrile seizures plus

Hundreds of mutations in the SCN1A gene have been found to cause genetic epilepsy with febrile seizures plus (GEFS+), which is a spectrum of seizure disorders of varying severity. These conditions include simple febrile (fever-associated) seizures, which start in infancy and usually stop by age 5, and febrile seizures plus (FS+). FS+ involves febrile and other types of seizures, including those not related to fevers (afebrile seizures), that continue beyond childhood. The GEFS+ spectrum also includes other conditions, such as Dravet syndrome (also known as severe myoclonic epilepsy of infancy or SMEI), that cause more serious seizures that last longer and may be difficult to control. These recurrent seizures (epilepsy) can worsen over time and are often accompanied by a decline in brain function.

The SCN1A gene mutations that underlie GEFS+ have a variety of effects on the function of the NaV1.1 channel. Some mutations change single amino acids in the channel, which alter the channel's structure. Others lead to the production of a nonfunctional version of the NaV1.1 channel or reduce the number of these channels produced in each cell. Still other mutations change single amino acids in critical regions of the channel. All of these genetic changes affect the ability of NaV1.1 channels to transport sodium ions into neurons. Some mutations are thought to reduce channel activity while others may increase it. It is unclear, however, how these genetic changes underlie the development of seizures or why they lead to a range of seizure disorders with varying severity.

Lennox-Gastaut syndrome

MedlinePlus Genetics provides information about Lennox-Gastaut syndrome

Malignant migrating partial seizures of infancy

MedlinePlus Genetics provides information about Malignant migrating partial seizures of infancy

Other disorders

A common change (polymorphism) in the SCN1A gene has been associated with the effectiveness of certain anti-seizure medications. This polymorphism, which is written as ICS5N+5G>A, alters a single DNA building block (nucleotide) in the SCN1A gene. Studies suggest that this polymorphism is associated with the maximum safe amount (dose) of the anti-seizure drugs phenytoin and carbamazepine. These drugs treat epilepsy by blocking sodium channels (such as NaV1.1) in neurons. A dose that is too small may not control seizures effectively, while a dose that is too large may cause unwanted side effects. Researchers are hopeful that doctors will be able to test for the ICS5N+5G>A polymorphism to help determine the safest and most effective dose of anti-seizure medications for each individual.

Other Names for This Gene

• GEFSP2
• HBSCI
• NAC1
• Nav1.1
• SCN1
• SCN1A_HUMAN
• sodium channel protein, brain I alpha subunit
• sodium channel, voltage gated, type I alpha subunit
• sodium channel, voltage-gated, type I, alpha
• sodium channel, voltage-gated, type I, alpha polypeptide
• sodium channel, voltage-gated, type I, alpha subunit

Genomic Location

The following list includes the most common signs and symptoms in people with Dravet syndrome. These features may be different from person to person. Some people may have more symptoms than others and symptoms can range from mild to severe. This list does not include every symptom or feature that has been described in this condition.

Signs and symptoms include:

• Many different types of seizures
• Sudden muscle jerking (myoclonus)
• Loss of developmental skills
• Intellectual disability
• Problems with walking
• Speech impairment
• Autistic-like behavior

The first seizures appear before one year of age and are often associated with fevers. In childhood, other types of seizures develop, and the frequency of seizures increases. Loss of developmental and cognitive skills may occur along with speech impairment and difficulty walking. In adulthood, the number of seizures may decrease, and nighttime seizures may occur. More serious complications include the risk of continuous seizures (status epilepticus) and sudden unexplained death.

Dravet syndrome is diagnosed based on the results of a clinical exam looking for specific symptoms that have been previously seen in this condition. Genetic testing can also be helpful.

Diagnosis is important because certain anti-seizure medications (sodium-channel agents) can make the seizures worse in Dravet syndrome.

Treatment for Dravet syndrome is focused on reducing the number and length of seizures. The seizures seen with Dravet syndrome are usually difficult to control, and people with this condition often need to take multiple anti-seizure medications. Certain types of anti-seizure medications (sodium-channel agents) can make the seizures worse, and should be avoided. New medications are being tested that are proven to be helpful in this condition.

Specialists who may be involved in the care of someone with Dravet syndrome include:

• Neurologist
• Developmental pediatrician
• Physical therapist
• Occupational therapist
• Speech therapist