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Dravet syndrome is a rare genetic developmental and epileptic encephalopathy that has an early onset, typically presenting within the first year of life. It was first described in 1978 and only received recognition by the International League Against Epilepsy in 1989. 

This disorder is typically suspected after an infant around the first year of life develops convulsive seizures. The most common presentation is that of a feverish child having persistent seizures that are either generalized or hemiclonic in nature.

Read more about Dravet syndrome etiology

Dravet syndrome differs from focal epilepsy on an important point: in Dravet syndrome, patients typically experience alternating types of unilateral seizures, like atonic, myoclonic,  focal, and atypical absences. However, abnormalities are usually absent in electroencephalographic studies and magnetic resonance imaging during early stages of the disease. 

Around 9 in 10 cases of Dravet syndrome have de novo mutations in the sodium channel gene SCN1A. This results in the haploinsufficiency of Nav1.1, the alpha-1 subunit of the sodium channel. Haploinsufficiency of Nav1.1, combined with frequent, recurrent seizures, drive the rise of comorbidities commonly associated with Dravet syndrome. 

“Along with drug-resistant epilepsy, intellectual disability, behavioral, language, and sleep disorders, as well as gait abnormalities, are the most common comorbidities observed in patients diagnosed with Dravet syndrome,” Gao and colleagues wrote in the Journal of Clinical Medicine. 

Drug resistance is a key concern in Dravet syndrome. The current strategy to help patients with this disorder achieve better outcomes is 2-fold: first, steps to facilitate early diagnosis such as genetic testing; and second, the expansion of the therapeutic arsenal aimed at limiting disease severity and progression. 

Current Therapies Used in Dravet Syndrome 

Pharmaceutical-grade cannabidiol received approval from the US Food and Drug Administration (FDA) for the treatment of seizures associated with Dravet syndrome in 2018. 

Two studies of note clearly demonstrate the potential of medical cannabidiol in treating seizures. The first was a study that involved patients who had 4 or more convulsive seizures despite being on antiseizure drugs. Around 43% of patients experienced a 50% or greater reduction in the frequency of convulsive seizures versus 27% on placebo. 

The second study involved patients who had at least 4 convulsive seizures being randomized to receive either cannabidiol 10 or 20 mg/kg/day or placebo for 14 weeks. Once again, the results indicate that patients who were on cannabidiol achieved significantly greater seizure control compared to patients who were on placebo. There was no significant difference between groups of patients receiving either dose of cannabidiol. 

Despite these promising findings on the use of cannabidiol in treating Dravet syndrome, “its exact mechanism of action is unknown,” according to Sullivan and Wirrell in Epilepsy Currents. Some have suggested that it works by enhancing neuronal inhibition via the GABAergic channels. Cannabidiol is typically well-tolerated, although some patients may experience adverse effects such as somnolence, diarrhea, or loss of appetite. 

Fenfluramine gained FDA approval for the treatment of seizures associated with Dravet syndrome. In 1 study, participants with Dravet syndrome were randomized to fenfluramine either 0.2 or 0.7 mg/kg/day or placebo. Results found that the mean monthly convulsive seizure frequency (MCSF) reduction was 41%, 70%, and 7.5% respectively. Another study had patients who were on stiripentol add on fenfluramine at a dose of 0.4 mg/kg/day or the placebo. The research team discovered that patients who were on both stiripentol and fenfluramine achieved a 54% reduction in MCSF compared to 7.5% in patients taking placebo. 

For the 3 main medications typically administered to patients with Dravet syndrome, cannabidiol, fenfluramine, and stiripentol, their mechanisms of action are likely to be multifactorial. Theories regarding how these drugs can minimize seizure frequency continue to abound. However, in the absence of significantly more potent medication, these 3 drugs form the backbone of Dravet syndrome care today. 

Potential Future Directions 

Two potential forms of future therapies are often discussed in the Dravet syndrome space. The first is the use of antisense oligonucleotide therapy to decrease nonproductive mRNA and simultaneously increase protein production. 

“As this therapy targets the underlying pathogenesis, it carries the potential benefit to not only reduce seizures, but also attenuate or prevent comorbidities including [sudden unexpected death in epilepsy,” Sullivan and Wirral wrote.

Read more about Dravet syndrome treatment

Another potential future approach to treating Dravet syndrome is the use of the adeno-associated virus 9 (AAV-9) to deliver gene therapy for the purpose of increasing transcription, which will then increase translation of the SC1A gene in inhibitory interneurons. In theory, gene therapy should be a 1-time approach, given that it addresses the underlying genetic anomaly driving pathology. 

Gene therapy is being heavily studied in a number of genetic diseases. In hemophilia, for example, scientists have already attained proof-of-concept that gene therapy is feasible; the challenge now is to carry out studies in human subjects that proves its efficacy as a therapeutic. At present, we are still a long way away from seeing this happen, either in hemophilia or in Dravet syndrome. 

Although we live in a time of great innovation, any therapeutic candidate must undergo the strictest testing prior to approval. Hence, although antisense oligonucleotide therapy and gene therapy hold great promise, efforts to move ahead faster are hampered by the many gaps in our knowledge surrounding Dravet syndrome, including the precise mechanism of its pathophysiology and the mechanism of action needed to counter pathology. 


Gao C, Pielas M, Jiao F, et al. Epilepsy in Dravet syndrome — current and future therapeutic opportunitiesJ Clin Med. Published online March 27, 2023. doi:10.3390/jcm12072532

Sullivan J, Wirrell EC. Dravet syndrome as an example of precision medicine in epilepsyEpilepsy Curr. Published online June 3, 2022. doi:10.1177/15357597221106281