Dravet syndrome

Dravet syndrome, previously known as severe myoclonic epilepsy of infancy (SMEI), is a type of epilepsy with seizures that are often triggered by hot temperatures or fever. It is treated with anticonvulsant medications. It often begins around six months of age. Dravet syndrome, previously known as severe myoclonic epilepsy of infancy (SMEI), is a type of epilepsy with seizures that are often triggered by hot temperatures or fever. It is treated with anticonvulsant medications. It often begins around six months of age. Dravet syndrome has been characterized by prolonged febrile and non-febrile seizures within the first year of a child’s life. This disease progresses to other seizure types like myoclonic and partial seizures, psychomotor delay, and ataxia. It is characterized by cognitive impairment, behavioral disorders, and motor deficits. Behavioral deficits often include hyperactivity and impulsiveness, and in more rare cases, autistic-like behaviors. Dravet syndrome is also associated with sleep disorders including somnolence and insomnia. 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. 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. Dravet syndrome appears during the first year of life, often beginning around six months of age with frequent febrile seizures (fever-related seizures). Children with Dravet syndrome typically experience a lagged development of language and motor skills, hyperactivity and sleep difficulties, chronic infection, growth and balance issues, and difficulty relating to others. 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. Febrile seizures are divided into two categories known as simple and complex. A febrile seizure would be categorized as complex if it has occurred within 24 hours of another seizure or if it lasts longer than 15 minutes. A febrile seizure lasting less than 15 minutes would be considered simple. Sometimes modest hyperthermic stressors like physical exertion or a hot bath can provoke seizures in affected individuals. 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. In most cases the mutations in Dravet syndrome are not hereditary and the mutated gene is found for the first time in a single family member. In 70–90% of patients, Dravet syndrome is caused by nonsense mutations in the SCN1A gene resulting in a premature stop codon and thus a non-functional protein. This gene normally codes for neuronal voltage-gated sodium channel Na(V)1.1. 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. The researchers found that loss of NA(V)1.1 channels was sufficient to cause the epilepsy and premature death seen in Dravet syndrome. There is some evidence that vaccines may be a trigger for Dravet syndrome in some children with this rare genetic mutation. The timing of the first signs and symptoms in Dravet syndrome also occur about the same time as normal childhood vaccinations, leading some to believe the vaccine was the cause, when it may simply be the inevitable progression of the disease. Some of the patients who put forth vaccine injury claims from encephalopathy were later found, upon testing, to actually have Dravet syndrome. The genotypic explanation of the disorder has been located on the specific voltage-gated sodium channel genes known as SCN1A and SCN2A. These genes are 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 mutation in either of these two genes will cause an individual to develop dysfunctional sodium channels, which are crucial in the pathway for sending chemical signals in the brain, causing the phenotypic display of myoclonic epilepsy from the individual. A properly functioning channel would respond to a voltage difference across the membrane and form a pore through which only sodium ions can pass. The influx of sodium induces the generation of action potential by temporarily changing the charge of the cell. 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. Currently, the SCN1A gene is the most clinically relevant; the largest number of epilepsy related mutations characterized thus far occur in this gene. Typically, a missense mutation in either the S5 or S6 segment of the sodium channel pore results in a loss of channel function and 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. According to the Dravet Syndrome Foundation, the diagnostic criteria for DS requires the patient to present with several of the following symptoms: