[5] The seizures experienced by people with Dravet syndrome become worse as the patient ages, as the disease is not very observable when symptoms first appear.
[5] This coupled with the range of severity differing between each individual diagnosed and the resistance of these seizures to drugs has made it challenging to develop treatments.
The effects of this disorder do not diminish over time, and children diagnosed with Dravet syndrome require fully committed caretakers with tremendous patience and the ability to closely monitor them.
[6] However, any seizure uninterrupted after 5 minutes, without a resumption of postictal (more normal; recovery-type; after-seizure) consciousness can lead to potentially fatal status epilepticus.
[7] In mouse models, these loss-of-function mutations have been observed to result in a decrease in sodium currents and impaired excitability of GABAergic interneurons of the hippocampus.
[7] The researchers found that loss of Nav1.1 channels was sufficient to cause the epilepsy and premature death seen in Dravet syndrome.
This gene is located on the long (q) arm of chromosome 2 at position 24.3 and code for the alpha subunit of the transmembrane sodium channel protein.
A properly functioning channel would respond to a voltage difference across the membrane and form a pore through which only sodium ions can pass.
When the gene is mutated, the eventually translated protein improperly folds its pore segment within the cell membrane because it has different amino acid chemistry, which renders the channel inactive.
It is also possible for a mutation to reduce the number of channels produced by an individual, which leads to the development of Dravet syndrome.
A heterozygous inheritance of an SCN1A mutation is all that is necessary to develop a defective sodium channel; patients with Dravet syndrome will still have one normal copy of the gene.
Mutations in the SCN1B gene have been found in several patients with Generalized Epilepsy with Febrile Seizures Plus (GEFS+), but very few with Dravet syndrome.
- PCDH19: This gene, located on the X chromosome, encodes protocadherin 19, a protein that helps neurons adhere to each other as they migrate to form networks and recognize other cells.
- STXBP1: This gene encodes the syntaxin-binding protein 1, which is involved in the vesicle fusion process (sacs containing substances like neurotransmitters) of the cell with the membrane.
According to the recommendations, second-line options include the ketogenic diet (KD), topiramate (TPM), and STP combined with VPA and CLB.
The usage of VPA, CLB, and TPM continued through childhood, adolescence, and adulthood, although that of STP decreased with age (31% in adults), according to the findings of a survey of caretakers of patients with DS on their experiences with management and health services.
According to reports, only a tiny percentage of adult patients receive treatment with sodium channel blockers, even though many of them had already been exposed to this class of ASM.
It has been shown that certain DS patients may respond to sodium channel blockers, especially LTG, with a greater frequency of seizures noted upon halting the medication.
[26] Stoke Therapeutics is currently evaluating the long-term safety and tolerability of repeated doses of STK-001 in patients with Dravet syndrome.
Change in seizure frequency, overall clinical status and quality of life will be measured as secondary endpoints in this open-label study.
Recently, the company announced positive results of MONARCH and ADMIRAL in which patients received 3 doses of STK-001 and were observed for 6 months.
This company has started a clinical trial in phase 1 and 2 to evaluate the safety and efficacy of ETX101 in participants with SCN1A-positive Dravet syndrome aged 6 to 36 months.
According to two studies, status epilepticus and sudden unexpected death in epilepsy (SUDEP) are the two most frequent causes of premature fatality among DS patients.
A prospective study of 37 individuals showed that, by reducing status epilepticus from occurring at a young age, the prognosis for seizures and mental impairment in DS patients can be improved.
[31][32] Although it is not clear whether people with Dravet syndrome are specially vulnerable to COVID-19 infection, 2020 publications have shown that affected individuals and their families have suffered some indirect consequences during the COVID-19 pandemic, such as healthcare barriers, loss of therapies or economic issues.
[35] Charlotte Figi, who was diagnosed as having Dravet syndrome, was the focus of a cause célèbre to provide a means for use of cannabidiol for persons with intractable seizures.