What is Dravet syndrome?

Answer: Dravet syndrome is a rare genetic disorder of the brain resulting in frequent seizures throughout life.

Image by  Gerd Altmann  from  Pixabay

Image by Gerd Altmann from Pixabay

Dravet syndrome is a nervous system disease that affects about 1 in every 16,000 people. The symptoms of Dravet syndrome include seizures that begin within the first year of life of an otherwise healthy baby, seizures that are triggered by high temperatures (ambient or body), slowed development despite typical growth in the first few months, and some lack of muscle tone or unstable gait and poor balance.

Causes of Dravet syndrome

One of the most well characterized abnormalities that contribute to Dravet syndrome is a mutation in the SCN1A gene. Inheritance of this mutated gene can be passed from one generation to the next through an autosomal dominant fashion. However, most cases of Dravet syndrome as a result of SCN1A mutation are sporadic, appearing even though there is no family history of the disease. This mutation is also seen in similar seizure related disorders, including Lennox-Gastaut syndrome, West syndrome, and intractable childhood epilepsy with tonic-clonic seizures.

The SCN1A gene encodes for a voltage gated sodium channel Nav1.1. These voltage-gated sodium channels are pore forming proteins that are embedded in neuronal membranes. They are able to change their biophysical properties depending on the electrical properties of the neurons. They open when the membrane becomes more positive, making them an essential part of the process of neuronal communication through sending action potentials. In Dravet syndrome, there are mutations in the protein causing them to have altered properties. One of the most characterized mutation is Thr226Met. As a result of this mutation, certain populations of neurons have a hyperpolarized shift in both the activation and inactivation potentials, meaning that the activation threshold is lower than in the neurotypical Nav1.1 channel. This leftward shift in rheobase may mean that the cell is excitable at lower potentials (SCN1A gain of function in early infantile encephalopathy.)

Treatment of Dravet syndrome

In some cases, Dravet syndrome can be treated with anti-epilepsy medications. Some of these drugs include the class of benzodiazepines such as clobazam. By acting as positive allosteric modulators at GABA receptors, these drugs increase the action of GABA, resulting in decreased neural activity.

Valproate is another drug that is often prescribed for epilepsy. Pharmacologically, it acts to decrease the action of some types of voltage-gated sodium channels, the proteins that are responsible for passing electrical signals from one neuron to the next. By decreasing the activity of some neurons, it can help to shut down the aberrant firing that is often seen in epilepsy.

Although Dravet syndrome is very resistant to therapeutic strategies, one novel approach has been shown to be effective at reducing seizures. One of the plant derived compounds found in marijuana called cannabidiol (CBD) has been effective at reducing the epilepsy seen in Dravet syndrome. Cannabidiol, like the other active compounds of marijuana such as tetrahydrocannbinol (THC) or cannabinol, affect the body by activating cannabinoid receptors, or CB receptors. These CB receptors are expressed widely throughout the body, including brain tissue, spinal cord tissue, and other non-neural cells. It is still unknown how activation of these CB receptors by CBD helps decrease the seizures that people with Dravet syndrome experience.

The Dravet syndrome foundation is one of the major sources of support for people who are affected by Dravet syndrome. They offer support, and can help connect you with other people and families who are likewise impacted by the disease.