What is Dravet syndrome?

What is Dravet syndrome?

A serious form of epilepsy, Dravet syndrome affects children from the first year of life. What are the clinical symptoms? How is this neurological disease managed? Explanations from Professor Stéphane Auvin, pediatric neurologist at the Robert Debré hospital in Paris.

First identified by Dr. Charlotte Dravet in 1978, Dravet syndrome is a rare neurological disease that affects children. “The first crisis, often very long, occurs in the first 6 months of the infant’s life”, underlines Professor Stéphane Auvin, pediatric neurologist at the Robert Debré hospital in Paris. Present across the globe, Dravet syndrome affects one case in 20,000 births.

A severe form of epilepsy in children

Although there are more than 80 forms of epilepsy identified, Dravet syndrome is characterized, at the beginning, by convulsive seizures.

Varying from one child to another in frequency and severity, epileptic seizures appear for the first time around the age of 5 to 6 months. “The onset of illness is noisy. This is a convulsive attack which can affect either both sides of the body or only one part, often in the context of fever, or after administration of a vaccine. The seizure can last from 20 minutes to an hour.specifies Professor Stéphane Auvin.

A month or a month and a half later, the same episode happens again. “In the first year, the attacks repeat themselves in the same way approximately every month., adds Professor Stéphane Auvin. Over time, the attacks last less long, even with treatment, but become more and more frequent (several attacks per week are possible).

Beyond 18 months, several types of seizures can be observed (convulsive seizures, absence seizures, myoclonus, etc.). In some cases, myoclonus is observed. It looks like startles. This is a very short and simultaneous contraction of an agonist and an antagonist muscle. “When it is epileptic myoclonus, the epileptic discharge originates from the cortex.explains the pediatric neurologist.

Different seizure triggers

If fever represents a well-identified triggering factor, exposure to light and visual stimulation (exposure to screens, to geometric figures, transition from light to dark and from black to light, for example) also play a role. in the occurrence of seizures, without being the cause of epilepsy. “In addition to fever, the administration of a vaccine or the simple fact of being sick, even without fever, can also induce seizures,” continues the doctor.

The child is also very sensitive to changes in temperature and heat, whether it is the temperature of the bath water or that of the room in which he or she is located. Intense physical exercise, strong emotions (whether positive or negative), stress, emotional shocks and sleep disorders also play a role in the appearance of seizures. “However, it is not a question of trying to control all areas of the child’s life so that no event disrupts his or her balance.specifies the pediatric neurologist.

Furthermore, if the administration of a vaccine is one of the triggering factors of a crisis, children must be able to be vaccinated like others. Having Dravet syndrome does not represent a contraindication to vaccination. “The families of these patients are often very worried about this. It is particularly important that they are well supported,” adds the specialist.

A genetic cause in 90% of cases

In the vast majority of cases, Dravet syndrome is linked to a “genetic accident”, not hereditary. “It is an alteration or mutation of the SCN1A gene located on chromosome 2, a gene responsible for electrical stability which has repercussions on the transmission of nerve impulses, causing epilepsy.continues the specialist.

Diagnosis du syndrome de Dravet

In infants and children, epileptic seizures are not uncommon. “As febrile seizures, which are epileptic seizures reaction to fever, are common (they affect 2 to 5% of children), there may be confusion between the first seizure occurring in a patient with Dravet syndrome and a febrile seizure. This confusion is sometimes responsible for a delay in diagnosis. points out the pediatric neurologist. However, unlike Dravet syndrome, these febrile attacks are very short (they last less than 5 minutes) and are mainly characterized by a loss of muscle tone (hypotonia). “After the appearance of two prolonged seizures, that is to say more than fifteen minutes before the age of one year, I recommend that parents not wait to consult a pediatric neurologist, especially as these seizures are very destabilizing. for the surroundings”, advises the specialist.

The diagnosis is established by tracing the history of the disease (age from which the attacks began, context of appearance of the attacks, characteristics of the attacks, the patient’s history, etc.). “Very often, the diagnosis is confirmed by a genetic test, by the presence of an anomaly in the SCN1A gene.continues the specialist.

Although it is useful, the genetic test does not have absolute value in confirming the diagnosis. Indeed, in 10% of cases, the genetic anomaly is not present. Furthermore, abnormalities in this gene can result in other forms of epilepsy. Depending on the case, an MRI or an encephalogram may also be prescribed.

Management of Dravet syndrome

To date, there is no treatment for this disease. It is simply possible to influence the severity and frequency of attacks so that they become less disabling in the patient’s life.

As for drug treatments, three molecules have marketing authorization in Europe: Stiripentol, Cannabidiol, and Fenfluramine. “Generally, the treatment combines several anti-seizure molecules and must be reassessed regularly by the doctor in charge of the child,” underlines the pediatric neurologist. These medications work well if prescribed correctly. On the other hand, as soon as treatment is stopped, the attacks return because the genetic cause of the disease remains present. “Good treatment should not be interpreted solely in terms of the number of attacks the patient has. It must make it possible to improve the quality of the subject’s life while ensuring that the side effects of the treatments do not alter their daily life. specifies the specialist.

Benzodiazepines are also prescribed anti-epileptic drugs. “This is emergency treatment in the event of a seizure. Once the seizure has started to last (after 5 minutes), the quicker we treat the seizure, the quicker it stops”, continues the doctor. These molecules can also be used as a basic treatment, that is to say with daily intake.

Currently, two avenues of clinical research are being studied. The first avenue aims to modify the consequences of the genetic anomaly. It involves the action of antisense oligonucleotides which will interfere with Messenger RNA. “The phase 2 clinical trial has been completed. We are now awaiting further investigations.”explains the specialist.

The second avenue of medical research is gene therapy: a gene is trapped in a virus which will be injected and will reach a subpopulation of neurons involved in Dravet syndrome. “The pre-clinical data are also encouraging but other experiments must be continued. continues Professor Stéphane Auvin.

The ketogenic diet: a way to reduce the frequency of attacks?

The ketogenic diet is one of the different possible therapeutic options but it does not constitute an alternative to medical treatment. “This diet has indeed demonstrated its effectiveness in certain syndromes. notes the doctor. It consists of removing 90% of sugars from daily diets. This does not mean, however, that sugars are toxic. Depriving a child suffering from epilepsy of sugar will not change the occurrence of seizures. “This will simply alter the child’s quality of life.” alert the doctor. The implementation of a ketogenic diet as well as its monitoring must be supported by health professionals.

As it is a neurological disease with repercussions at multiple levels, the management of Dravet syndrome involves a multidisciplinary approach involving several specialties: neuropediatrics, physiotherapy, psychomotor skills, occupational therapy, speech therapy, psychology, etc. “It is a matter of setting up, on a case-by-case basis, an environment adapted to the child according to the specificities of each person, whether in a suitable solar environment or within a medico-social institute.

Impact of illness on daily life

In all affected subjects, Dravet syndrome causes developmental delays: language difficulties, poor coordination of limbs, behavioral disorders, cognitive disorders, etc. The SCN1A gene plays a role in cognitive functions: language, food selectivity, speech disorders. sleep, motor attention, impulse. “Beyond epileptic seizures, Dravet syndrome is a global neurological disease.summarizes the specialist.

Balance disorders, motor impairments, walking difficulties, Dravet syndrome can also be expressed in certain cases by scoliosis, or even deformities of the spine.

What to do in the event…