What Is Dravet Syndrome?

Dravet syndrome is a rare, severe, and incurable epilepsy syndrome that begins in early childhood. It was previously known as severe myoclonic epilepsy of infancy (SMEI). Dravet syndrome is characterized by prolonged, multiple seizures frequently brought on by increased body temperature. A mutation of the SCN1A gene, which controls electrical signals in the brain, is believed to be the cause of Dravet syndrome. However, the disease can occur in someone who lacks that mutation.

One in every 20,000 to 40,000 people has Dravet syndrome, according to the Epilepsy Foundation. Seizures typically begin at 6 to 10 months of age. Dravet syndrome is also known as epileptic and developmental encephalopathy because the seizures and abnormal brain activity are associated with developmental delays and cognitive impairment.

Unlike other forms of epilepsy, Dravet seizures are often hard to control and are often resistant to epilepsy medications. For that reason, people with Dravet syndrome may have a poorer prognosis than people living with other types of epilepsy. Estimates of mortality range from 15 percent to 20 percent, according to the Dravet Syndrome Foundation. Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in people with uncontrolled seizures and usually occurs during sleep.

Dravet Syndrome Symptoms and Seizure Types

Children with Dravet syndrome may experience several types of epileptic seizures that increase in frequency and duration as they age.

Febrile Seizures

Febrile seizures can occur in children with or without Dravet syndrome and are typically triggered by a high body temperature or childhood illness. They are usually the first seizures a child with Dravet syndrome may experience. Febrile seizures appear as stiffness and jerking (known as a tonic-clonic seizure) or repeated jerking (a clonic seizure).

In most children, febrile seizures last a few minutes. In those with Dravet syndrome, the seizures can be more severe and last 15 or 30 minutes. The more febrile seizures a child experiences, the more likely they will develop epilepsy.

Febrile seizures in children with Dravet syndrome often progress to myoclonic seizures at age 4 or 5. These seizures are drug-resistant.

Myoclonic Seizures

Myoclonic seizures appear as brief shock-like jerks of a muscle or group of muscles in 85 percent of children with Dravet syndrome. They typically occur before age 2. Myoclonic seizures can affect the entire body or just one part of the body. They usually last a fraction of a second, though some people experience them in clusters.

Focal Aware or Impaired Awareness Seizure

Focal seizures, which affect one side of the brain, become common in children with Dravet syndrome around age 2. The person may be aware — or partially aware — of their surroundings, but can’t move or respond. Automatic movements, such as lip smacking or hand fumbling, may occur.

Atypical Absence Seizures

Atypical absence seizures are brief (under 30 seconds) and cause a short period of “blanking out” or staring into space. They typically occur in children 2 years of age or older. Falls are more common during an atypical absence seizure than in a typical absence seizure.

Atonic Seizures

Atonic seizures feature a brief lapse in muscle tone. Atonic seizures usually last under 15 seconds and may temporarily paralyze a part of the body. Atonic seizures are often called “drop attacks” because the affected person may suddenly drop their head or fall down.

Status Epilepticus

Seizures lasting longer than five minutes or occurring too close together for the person to recover are called status epilepticus. Status epilepticus can be convulsive or nonconvulsive. Each type affects awareness and body movements differently, but both are life-threatening and require emergency medical intervention.

Seizure Triggers

Seizure triggers among children with Dravet syndrome include:

• Temperature changes, such as coming out of a hot bath

• Emotional stress or excitement

• Flashing images on TV or computer screens (also known as photosensitive seizures)

Dangers of Seizures With Dravet Syndrome

Seizures can have life-threatening consequences for people with Dravet syndrome. Risk of sudden unexpected death in epilepsy (SUDEP) in Dravet syndrome is higher than in other types of epilepsy. Status epilepticus and accidental death from injury or drowning are additional causes of mortality associated with Dravet syndrome.

The best way to prevent death due to SUDEP and status epilepticus is to control seizures as much as possible. Your medical team can find the best treatment plan for your child with medication, changes to diet or nutrition, or alternative approaches. Children with Dravet syndrome generally need 24-hour care.

Developmental Delays With Dravet Syndrome

Children with Dravet syndrome typically have normal development in the first year of life. As seizures increase, development often slows, and they may begin exhibiting signs of cognitive impairment. By ages 2 or 3, speech delay is frequently seen, and cognitive issues become more severe. Gait problems, including crouched walking and lack of coordination (ataxia), are also common and may decrease mobility in adolescence. Physical, occupational, and speech therapy are recommended for developmental support. Children with Dravet syndrome may also have autism spectrum disorder or attention deficit hyperactivity disorder (ADHD).

Other Health Issues With Dravet Syndrome

More than 60 percent of people with Dravet syndrome experience dysautonomia. Symptoms of dysautonomia include problems with temperature regulation, decreased sweating, fast heart rate (tachycardia), and sluggish digestion and blood circulation. About 60 percent of children with Dravet syndrome also show growth and nutrition issues. Many have other health problems, including sleep issues and frequent infections.

Causes of Dravet Syndrome

More than 80 percent of children with Dravet syndrome have a mutation of the sodium voltage-gated channel alpha subunit 1 (SCN1A) gene. A mutation on the SCN1A gene prevents sodium channels in neurons of the brain from working correctly. Other genetic mutations may be associated with Dravet syndrome too. About 90 percent of gene mutations are new, or de novo, mutations. This means the mutation has not been inherited from a parent, but is a new, first-time mutation in the child. In families with inherited SCN1A mutations, the risk of each additional child being born with Dravet syndrome is 50 percent.

Dravet Syndrome Diagnosis

If your child experiences seizures, you may be referred to a pediatric neurologist who treats epilepsy. The diagnostic process will start with a thorough medical history and may include an electroencephalogram (EEG) to analyze the brain’s electrical activity, magnetic resonance imaging (MRI) scans, or other testing. If there is a high degree of suspicion based on medical history and imaging, the doctor may order a blood test to detect the SCN1A mutation to confirm the diagnosis.

Many children with Dravet syndrome are initially misdiagnosed. That is because EEG and MRI results typically appear normal in babies with Dravet syndrome and may not show abnormal activity until the child is 18 months old.

Dravet syndrome may also be mistaken for common childhood febrile seizures. Some studies suggest that it can take almost five years from seizure onset to get a diagnosis of Dravet syndrome.

Genetic testing can help diagnose Dravet syndrome. Guidelines recommend genetic testing for Dravet syndrome if children experience one or more of the following symptoms:

• Two or more prolonged seizures by age 1.

• One prolonged seizure and sustained, rhythmic jerking of one side of the body (hemi-clonic seizures) by age 1.

• Two seizures that affect alternating sides of the body.

• Seizures before 18 months and myoclonic or absence seizures later on.

Dravet Syndrome Treatment

People with Dravet syndrome experience a wide range of severity and seizure types. For this reason, treatment varies. Although there is no cure for Dravet syndrome, treatment is aimed at finding the best combination of antiepileptic drug therapies (AED) to treat chronic seizures. Usually multiple seizure medications are needed to treat the variety of seizure types that present with this syndrome.

First-Line Treatments

Antiseizure medications are the first therapies prescribed for people with Dravet syndrome. They include Depakene (valproic acid) — to prevent recurrence of febrile and long lasting seizures — or Onfi (clobazam).

Second-Line Treatments

If first-line treatments are not effective, a neurologist may prescribe second-line medications including Qudexy XR, Topamax, or Trokendi XR (topiramate). In 2018, the U.S. Food and Drug Administration (FDA) approved the antiseizure drug Diacomit (stiripentol) for use with clobazam in children 2 years and older with drug-resistant Dravet seizures. As many as 71 percent of children treated with Diacomit in the clinical study had a greater than 50 percent decrease in seizures, compared to 5 percent treated with placebo.

The ketogenic diet is also considered a second-line treatment for Dravet syndrome. Studies in children whose seizures were not otherwise controlled showed that half saw at least a 50 percent reduction in seizures. As many as 15 percent of children became seizure-free on the ketogenic diet. There is also some evidence that a ketogenic diet is linked to improvements in behavior and cognition in children with Dravet syndrome.

Third-Line Treatments

Antiseizure and anticonvulsant medications may be prescribed when first- and second-line treatments fail. These medications may include Klonopin (clonazepam), Keppra (levetiracetam), Zonegran (zonisamide), and Zarontin (ethosuximide). Another medication that is rarely prescribed due to limited availability is potassium bromide.

Vagus Nerve Stimulation (VNS)

VNS is FDA-approved as an add-on therapy for adults and children age 4 and up. Nerve stimulation is used to treat focal or generalized seizures that do not respond to medications. A device implanted in the chest sends electrical signals through the vagus nerve to help control seizures. A 2017 meta-analysis of 13 studies comprising 68 participants with Dravet syndrome reported that 53 percent of people treated with nerve stimulation showed a minimum 50 percent reduction in seizures.

Epidiolex (Cannabidiol)

An oral form of cannabidiol (CBD), Epidiolex is the first FDA-approved drug to control Dravet-related seizures. In a 2017 clinical trial of 120 young adults and children with Dravet syndrome, 43 percent treated with Epidiolex had a more than 50 percent decrease in seizures, compared to 27 percent of those treated with placebo.

Rescue Medications for Dravet Syndrome

Rescue medicines can be used to treat clusters of seizures or seizures that last longer than normal. These are not a replacement for preventative treatment, which is taken on a regular schedule. Rescue treatments work quickly in the brain to end seizures and avoid emergencies. The most commonly prescribed rescue medicines are fast-acting benzodiazepines such as Valium (diazepam), Ativan (lorazepam), and Versed (midazolam). These rescue medications are given orally, under the tongue (sublingual), between the cheek and gum (buccally), or sprayed into a nostril (nasal spray). Diastat, the rectal form of diazepam, is most often prescribed for children.

Developing a seizure response plan is important in helping manage emergency situations. The Epilepsy Foundation offers information and tools for creating a seizure response plan.

Clinical Trials

Fenfluramine is a medication currently being evaluated for efficacy in treating Dravet syndrome. Clinical trial results published in December 2019 were promising. The study of 173 children showed a reduction in monthly convulsive seizure frequency among those treated with the study treatment compared to those who received the placebo.

Treatments To Avoid

Certain common anticonvulsant drugs can worsen seizures in some people with Dravet syndrome. They include such sodium channel blockers as Tegretol (carbamazepine), Trileptal (oxcarbazepine), Aptiom (eslicarbazepine) Lamictal (lamotrigine), Sabril (vigabatrin), and Dilantin (phenytoin).

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