Causes of Dravet Syndrome

Dravet syndrome (also known as severe myoclonic epilepsy of infancy) is a severe form of epilepsy, which usually appears during the first year of life as fever-related seizures.

As the disease progresses, other types of seizures also may occur, such as myoclonus, characterized by brief jerks of a muscle or group of muscles, and status epilepticus, when seizures do not stop or occur close together.

Children with Dravet syndrome have normal development when seizures begin. However, as seizures continue, they begin to show some level of developmental disability. Other symptoms may also occur, including changes in appetite, balance, and gait, which is the child’s manner of walking.

What causes Dravet syndrome?

Around 80-90% of Dravet syndrome cases are caused by mutations in the SCN1A gene. Hundreds of mutations in this gene have been identified that are linked to seizures caused by high fever.

The SCN1A gene provides instructions to build a protein that forms a subunit of a sodium channel called NaV1.1. This sodium channel is found on the surface of nerve cells and controls the influx of sodium ions into the cells, activating them and allowing them to pass nerve signals onto other cells.

There are different types of nerve cells. Some are excitatory and send signals that activate other neurons, and some are inhibitory, sending signals that silence other neurons.

Scientists do not fully understand how the mutations in the SCN1A gene cause seizures. But they think one way could be by impairing the activity of a type of inhibitory neurons called GABA neurons, leading to no inhibitory signals being fired. The result is the overactivation of the nervous system, with the uncontrollable firing of signals and the development of seizures.

Some SCN1A mutations were found in less severe forms of epilepsy, meaning that not all children with these mutations will develop Dravet.

There also may be other ways in which the mutations alter the functioning of the sodium channels and the nervous system, leading to seizures. More research is needed, scientists say.

How is Dravet syndrome inherited?

Although most cases of Dravet are the result of de novo or new mutations, up to 10% are familial and inherited by children from their parents.

Inheritance of Dravet syndrome follows an autosomal dominant pattern. This means that a single copy of the mutated SCN1A gene, inherited either from the mother or the father, is sufficient to cause the disease. In such cases, a person affected by the condition has a 50% risk of having a child affected by Dravet syndrome.

Children who inherit the mutated SCN1A gene will have Dravet, however they may be more or less affected than their parents. In some cases, the parent has a milder form of epilepsy or no neurological symptoms, while the child has Dravet syndrome.

Other genetic causes of Dravet syndrome

In around 10 to 20% of Dravet cases, the genetic cause remains unknown, and other genes likely are implicated.

Genes such as GABRA1, GABRG2SCN1BSCN2ACHD2HCN1, and STXBP1 are thought to be involved, but the clinical presentation in these cases is often different from that of Dravet.

 

Last updated: May 28, 2021

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