Dravet syndrome

What is Dravet syndrome?

Dravet syndrome is a rare and severe form of epilepsy. At some point in their first year, children with Dravet syndrome begin to have frequent, prolonged seizures that are difficult to control with standard epilepsy treatments.

At first, children with Dravet syndrome appear to be developing normally. As seizures begin and continue, their cognitive and motor development may slow or stop. The severity of these developmental delays varies from child to child. Some children experience periodic developmental or cognitive improvement, but most have some degree of lifelong disability.

Current treatment options for Dravet syndrome include medications, special diets and an implantable device (a therapy called vagal nerve stimulation). It's often challenging to find a treatment or combination of treatments that completely control the seizures.

Recent studies suggest Dravet syndrome affects around 1 in 15,000 children. Some 3 to 8% of children who have seizures in their first year of life are eventually diagnosed with the syndrome.

The Pediatric Epilepsy Center of Excellence is dedicated to diagnosing and treating all forms of epilepsy, including Dravet syndrome, from birth to adolescence. The National Association of Epilepsy Centers designated our San Francisco clinic a level 4 facility – the highest possible rating – for our highly specialized, comprehensive care. The center uses advanced diagnostic tools and assessments to accurately diagnose Dravet syndrome and develop personalized treatment plans for each child.

Research to uncover new treatments is underway, and children who don't improve with available therapies may be eligible to participate in our clinical trials. We also offer support services, such as child psychology, special education and group therapy sessions.

Causes of Dravet syndrome

More than 80% of patients with Dravet syndrome have a mutation in a gene called SCN1A. This mutation affects the brain's sodium channels, which are important for regulating the firing of nerve cells. There are other genetic mutations that also may cause Dravet syndrome.

These gene mutations usually occur spontaneously during fetal development and are not inherited from a parent. However, there are rare cases of families having more than one child with Dravet syndrome.

Symptoms of Dravet syndrome

The first sign of Dravet syndrome is usually a convulsive seizure triggered by a fever. First, the body stiffens, then one or both sides of the body start to jerk repeatedly. This typically occurs when the child is around 5 to 8 months old.

Children with Dravet syndrome go on to have other types of seizures in the weeks or months after the first event. The seizures tend to be long (more than two minutes) and difficult to control with medication. They may be triggered by infections, changes in body temperature, flashing lights or other visual stimuli, as well as emotional stress or excitement.

Between the ages of 1 and 5 years, many children with Dravet syndrome begin to show signs of developmental delay as well as other health issues that have been associated with the condition. These can include:

• Behavioral issues, such as hyperactivity, irritability and traits associated with autism spectrum disorder
• Frequent infections
• Poor coordination
• Slow speech development
• Slow growth and poor weight gain
• Unsteady gait

Diagnosis of Dravet syndrome

Many children with Dravet syndrome are initially misdiagnosed. This is because the diagnosis depends on the child's history of seizures and other symptoms that emerge as the seizures progress. Another complication is that the results of tests typically used to evaluate epilepsy – magnetic resonance imaging (MRI) and electroencephalography (EEG) – initially appear normal in babies with Dravet syndrome. Experts believe some children with Dravet syndrome are never correctly diagnosed.

At first Dravet syndrome may be mistaken for febrile seizures, a common type of childhood seizure triggered by a fever. Unfortunately, medications used to treat febrile seizures can worsen seizures in children with Dravet.

Experts recommend genetic testing for children who have had any of the following:

• Two or more prolonged seizures (more than 10 minutes each) before the child turns 1
• One prolonged seizure and a hemiclonic seizure (rhythmic jerking of one side of the body) before the age of 1
• Two seizures that affect alternating sides of the body
• One or more seizures before the child is 18 months old, followed by myoclonic seizures (isolated jerking of a muscle or muscle group), absence seizures (brief periods when the child appears to stare into space, also called petit mal seizures) or both

Genetic blood tests can screen for SCN1A mutations and a few other gene mutations linked to Dravet syndrome. However, these tests are not 100% conclusive because they don't screen for all mutations that cause Dravet syndrome and because SCN1A mutations can also cause other, less severe forms of epilepsy. And some cases of Dravet syndrome don't have a clear genetic cause.

There is a strong chance that children who meet most of the following criteria have Dravet syndrome, even if they don't have an SCN1A mutation:

• Normal development before the first seizure
• Two or more seizures, with or without fever, before they turn 1
• Two or more seizures that last more than 10 minutes
• Myoclonic, hemiclonic or tonic-clonic seizures (sudden stiffening and jerking of the whole body, also called grand mal seizures)
• Seizures that don't respond to epilepsy medications and that continue past age 2

Treatment of Dravet syndrome

Because Dravet syndrome is so rare, it can be difficult to find a pediatric neurologist who has experience in treating it. The Dravet Syndrome Foundation maintains a searchable listing of doctors who have treated patients with Dravet syndrome and related epilepsies.

When caring for children with Dravet syndrome, our main goal is to achieve the best possible seizure control. We also want to prevent a life-threatening type of prolonged seizure called status epilepticus (a seizure that lasts longer than five minutes or a string of seizures occurring one after the other). By minimizing the risk of these severe events, we hope to improve quality of life for kids as well as their families.

To reduce the frequency and severity of seizures, patients must avoid seizure triggers and take medications. A ketogenic diet – low in carbohydrates and high in fat – may also help. Surgery is generally not recommended, but in some cases, an implantable device called a vagal nerve stimulator may reduce seizures.

Working with experts, such as a speech therapist, physical therapist and occupational therapist, can help improve patients' motor and cognitive development. Psychological and social support for the whole family is also important.

Avoiding seizure triggers for Dravet syndrome

People with Dravet syndrome tend to be more sensitive to seizure triggers than those with other types of epilepsy, so it's especially important that they avoid these common triggers:

• Fevers (which should be treated with fever reducers, such as ibuprofen or acetaminophen)
• Flashing lights
• Overheating (usually from hot baths or exercise)
• Stress or overexcitement
• Sudden temperature changes in the environment (hot or cold)
• Visual patterns, such as stripes and other contrasting patterns

Fevers caused by vaccines sometimes trigger a seizure. Around 50% of first seizures in patients with Dravet syndrome are triggered by a vaccine-induced fever. (It's important to understand that vaccines don't cause Dravet syndrome or change how the condition progresses.) Your child's doctor may recommend giving your child a fever reducer before a vaccination and during the following 24 hours to prevent vaccine-related fever.

Medications for Dravet syndrome

Every Dravet patient is different, and medications that work for one child may not work for another. Generally, we introduce medications in a systematic order, beginning with those that have helped the largest number of patients. This helps us determine the best treatment regimen for each child.

The following medications are first-line treatments for Dravet syndrome, meaning they've benefited the most patients:

• Clobazam (Onfi, Frisium, Urbanyl)
• Valproic acid (Depakote, Depakene, Epilim, Epival)
• Topiramate (Topamax)

If first-line treatments fail, your child's neurologist may try second-line medications:

• Stiripentol (Diacomit)
• Levetiracetam (Keppra)

Some common epilepsy drugs can worsen seizures in people with Dravet and should be avoided. These include:

• Carbamazepine (Tegretol, Carbatrol)
• Oxcarbazepine (Trileptal)
• Lamotrigine (Lamictal)
• Phenytoin (Dilantin, Epanutin)
• Vigabatrin (Sabril, Sabrilan, Sabrilex)

Children who experience status epilepticus must be treated with certain medications to try to stop the seizure; these are often called "rescue medications." Your child's doctor may prescribe a rescue medication – typically a benzodiazepine, such as diazepam (Diastat), midazolam (Versed) or lorazepam (Ativan) – so you'll have it on hand in case of status epilepticus.

Ketogenic diet for Dravet syndrome

The high-fat, low-carb ketogenic diet can be helpful for some children with Dravet syndrome, especially if their seizures aren't responding to medication. Studies have shown that a large percentage of Dravet patients have less frequent seizures while on the diet. Some research suggests that a ketogenic diet is also linked to improvements in behavior and cognition.

Ketogenic diets should designed by the patient's neurologist and a dietitian experienced in care for Dravet syndrome.

Vagal nerve stimulation for Dravet syndrome

If medications aren't working, vagal nerve stimulation may be considered. This involves implanting a small device in the child's neck, around the vagus nerve. The device regularly sends mild electric signals from the vagus nerve up to the brain, which may interrupt a seizure or prevent one from starting.

Experimental treatments for Dravet syndrome

Researchers at UCSF and other institutions are actively seeking new treatments for Dravet syndrome. If standard options fail, your child may have the opportunity to participate in a clinical trial investigating a promising drug or procedure.