An Overview of Dravet Syndrome

Dravet syndrome is a rare disorder characterized by seizures and developmental problems. The seizures begin before age 1. The cognitive, behavioral, and physical problems begin around age 2 or 3. Dravet syndrome is a lifelong condition.

The disease is associated with a genetic defect in the SCN1A gene, although it can occur without the genetic defect. It is diagnosed based on a child’s clinical signs and symptoms, and the diagnosis can be supported with diagnostic testing.

Seizures caused by Dravet syndrome are particularly difficult to control. The anticonvulsant treatments that are commonly used for most seizure disorders are usually not effective for decreasing the seizures that occur in Dravet syndrome, but research is ongoing and new strategies and options have become available.

Symptoms

Seizures are the earliest symptom of Dravet syndrome. Developmental problems, as well as seizures, generally worsen as a child gets older. 

Symptoms of Dravet syndrome include:

• Seizures: Seizures are often associated with fevers, although they can occur without fevers. There are several seizure types that typically occur in Dravet syndrome, including myoclonic seizures, tonic-clonic seizures, and non-convulsive seizures. Prolonged seizures and status epilepticus are characteristic of the disorder as well. In fact, the first seizure may be particularly long in duration. 
• Seizure triggers: People with Dravet syndrome may have seizure photosensitivity, which is a tendency to have seizures in response to bright or flashing lights. Additionally, a person who has Dravet syndrome may be prone to having seizures in response to changes in body temperature. 
• Ataxia (balance problems): Difficulties with coordination and walking, known as ataxia, begin in childhood and continue in adolescence and adulthood.
• Motor impairment: People living with Dravet syndrome are described as having a crouched position when walking. Low muscle tone is often present, which can manifest as muscle weakness.
• Cognitive impairment: Children may develop speech and cognitive problems that last throughout life. There can be a range of cognitive abilities with Dravet syndrome, and some people with the condition have a higher capacity for learning than others.
• Behavioral problems: Children and adults living with Dravet syndrome may exhibit irritability, aggression, or behavior that resembles autism.
• Infections: People with Dravet syndrome are prone to infections. 
• Sweating and temperature regulation irregularities: People with Dravet syndrome may experience alterations in the autonomic nervous system, particularly causing diminished sweating and excessively high or low body temperatures.
• Bone problems: Dravet syndrome is associated with frail bones and a predisposition to bone fractures.
• Heart rhythm irregularities: About one third of people living with Dravet syndrome have an irregular heartbeat, such as a rapid heart rate, a slow heart rate, or another irregularity, such as a prolonged QT interval.

Prognosis

Dravet syndrome is a lifelong condition and the symptoms do not improve. There is an increased risk of early death, often related to injuries due to seizures. People with Dravet syndrome are also more likely to experience sudden unexpected death in epilepsy (SUDEP), a condition in which unexpected death occurs, usually during sleep.

Causes

Dravet syndrome is believed to be caused by a defect in the function of the sodium channels and is described as a form of channelopathy. Sodium channels regulate brain and nerve function. A defect in the function of sodium channels can cause a variety of problems, including erratic brain activity, manifesting as seizures, and defective communication between brain cells, manifesting as developmental impairment.

Genetics

About 80 percent of people who have Dravet syndrome have a defect in chromosome two in the SCN1A gene, which codes for sodium channels. This defect occurs in a hereditary pattern, and the mutation can also arise for the first time in an affected child.

Diagnosis

Dravet syndrome is diagnosed based on a physician’s clinical evaluation. Diagnostic studies can support the diagnosis, but they do not confirm or exclude it. According to the Dravet Syndrome Foundation, clinical characteristics of Dravet syndrome include at least four of the following five characteristics:

• Normal cognitive and motor development before the first seizure occurs
• Two or more seizures before age 1
• A combination of myoclonic, hemiclonic, or generalized tonic-clonic seizures
• Two or more seizures lasting longer than 10 minutes
• A lack of improvement with standard anticonvulsant treatment and continued seizures after age two

Diagnostic Tests

• Electroencephalogram (EEG): EEG is typically normal when a person who has Dravet syndrome is not having a seizure, especially in very young children. EEG will show abnormalities consistent with seizure activity during a seizure. In later childhood and throughout adolescence and adulthood, the EEG may show a pattern of slowing in-between seizures as well.
• Brain MRI: Typically, the brain MRI of a person with Dravet syndrome is expected to be normal. It can show atrophy (thinning) of the hippocampus or the whole entire brain during adulthood.
• Genetic testing: Genetic testing can identify the SCN1A mutation that is most often present among people with Dravet syndrome. It has been noted in a mosaic pattern, which means that a person can have some cells with the mutation, and some without it.

Treatment

There are a number of different problems that a person with Dravet syndrome can expect to experience, and all of them are difficult to treat. Treatment for the physical, cognitive, and behavioral problems of Dravet syndrome is individualized, and may include physical therapy, speech therapy, and behavioral therapy.

The seizures are not easily controlled. Typically, anticonvulsants used in Dravet syndrome include a combination of valproate, clobazam, stiripentol, topiramate, levetiracetam, and bromides. A ketogenic diet and vagus nerve stimulation are considered for treatment of the seizures as well.

Cannabidiol

In June 2018, the United States Food and Drug Administration (FDA) approved Epidiolex (cannabidiol) for treatment of Dravet syndrome as well as another epilepsy syndrome, Lennox Gastaut syndrome. Earlier studies showed that children with Dravet syndrome experienced a decrease in seizure frequency with Epidiolex and were able to tolerate the medication.

Medications That Worsen Dravet Syndrome

Standard anticonvulsants believed to have an effect on sodium channels include carbamazepine, oxcarbazepine, phenytoin, and lamotrigine. These may worsen, rather than improve, seizures in Dravet syndrome.

A Word From Verywell

If your child has been diagnosed with Dravet syndrome, it can feel like a challenging situation. Your child will need close management and care throughout his or her life. Many of the symptoms of Dravet syndrome can partially improve with proper treatment. Treatment strategies may need to change as your son or daughter grows physically, and as their condition improves or worsens with age.

As with many rare diseases, the sense of isolation and of not knowing what to expect can be overwhelming. Some families find it helpful to connect with others who may be experiencing the same challenges through support groups and patient advocacy groups.