• Dravet syndrome discoverer, Dr. Charlotte Dravet, highlights importance of genetic studies in the improvement of diagnosis, which, according to her, has become possible earlier and has been given a strong basis.
• “When the parents of a kid with epilepsy are well informed about the meaning of the genetics, they understand it is not their fault, but it is an accident they could not avoid, and most are relieved when they know the diagnosis and the cause of the disease”, assures Dr. Dravet.
Madrid, June 23, 2023.
When we asked Dra. Charlotte Dravet about the concept of personalized medicine, she assures us that “it is and has been the principle of the medical practice for all physicians. It is by means of their accurate observation of each patient they had to treat that the physicians could reach a diagnosis when they only had this observation without technical help”.
And indeed, she first described Dravet syndrome when she observed that many of the patients who came to her office did not have the typical symptoms of the known forms of epilepsy but had certain unique features.
Dr. Charlotte Dravet, a French psychiatrist and epileptologist, described the disease in 1978. In her words and gestures when she talks about patients and their families, she shows the vocation and commitment that have always accompanied her. She states that the concept of personalized medicine is not a revolution, but rather that the concept has been a part of healthcare for many years. “Already the treatment should be adapted to each patient taking into account the type of response he had to the drugs, the diets and the non-pharmacological means”, assures.
For her, the novelty comes from the introduction of two elements: the possibility to consider also the genetic background of each patient, and the arrival of numerous ASM (anti-seizure medication) which have enriched the therapeutic “arsenal”.
Diagnosis of Dravet syndrome is often delayed
Dravet syndrome is a rare, genetic epileptic encephalopathy that gives rise to seizures that don’t respond well to seizure medications. It begins in the first year of life in an otherwise healthy infant at this time. However, during the course of the disease epilepsy is associated with a delayed developement, behaviour disturbances, and motor impairment.
Diagnosis is often delayed. MRI (magnetic resonance imaging) and EEG (electroencephalogram) tests are usually normal in infants at first. About 8 out of 10 people with this syndrome have a gene mutation in SCN1A that causes problems in the way ion channels in the brain work.
This mutation is most often not inherited from the parents. It is considered a “de novo” or “new” mutation in the child. Not all SCN1A mutations are associated with Dravet syndrome.
Dr. Charlotte Dravet notes that “even in the so-called “developed” countries there are not specialized doctors and medical services in each region who are aware of the different types of epilepsy in children and who are able to distinguish the different types of encephalopathy. The reference centers are not well known and sometimes difficult to reach. That is an explanation of the delayed diagnosis for some patients.”
The importance of genetics in this epilepsy
“The incorporation of genetics has mainly improved the diagnosis which has become possible earlier and has been given a strong basis. When the parents are well informed about the meaning of the genetics – that is to say this disease is not hereditary – they understand it is not their fault, but it is an accident they could not avoid, and most are relieved when they know the diagnosis and the cause of the disease”, states Dr. Dravet.
The expert tell us that when there is no diagnosis in infancy or childhood there are two main consequences. One is that the parents and doctors continuously ask for many investigations which are heavy for the patients and the families and expensive for the society, and at the end produce only disillusion. The other is that the doctors prescribe treatments with ASM which can be contraindicated and can provoke worsening of the seizures and deleterious effects on behavior and development.
De Lange and her coworkers, in 2018, have realized an accurate study which demonstrated the influence on cognitive development of the contraindicated ASM when given during a long period in the five first years of life in a cohort of 104 Dutch participants. Their statistical analysis showed that there was a significant lower intelligence quotient in patients treated with contra-indicated ASM during more than 11 months when compared to those treated during less than 11 months (P = .001).
“Having a diagnosis takes off the burden of many unanswered questions from parents: “Why? Why him/her? Are we responsible? How will be his/her future?”. Knowing the genetic origin of an epilepsy often allows to discard the perspective of a surgical treatment which should be an error. Some patients with Dravet syndrome have been operated on but without no improvement, even with an aggravation, because they do not have a unique epileptogenic zone but a diffuse hyperexcitability”, adds the doctor.
The future of Dravet syndrome
With respect to new treatments options, the doctor thinks that there are still some obstacles and difficulties. In any case, “to obtain results not only on the seizures but also on the impairment of the development, this type of treatment should be started at the beginning of the disease as soon as the diagnosis has been confirmed. Thus, it will be necessary to quickly decide to treat the little patient only with ASM or with a genic procedure, probably not later than during the second year”.
Dr. Charlotte Dravet concludes that, in order to allow the small patients to achieve the best possible development and behavior, it is mandatory to add to the ASM therapies which aim at optimize the cognitive, motor and relational development such as speech therapy, psychomotricity, physiotherapy, ergotherapy, as well as socialization in kindergardens, school, and sport among others.
