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Diagnosis and Causes of Dravet Syndrome | Neurology

What is dravet syndrome?

Dravet syndrome is rare drug-resistant epilepsy that begins in the first year of life in an otherwise healthy baby. It is for life. It usually offerings with a prolonged seizure with a fever that affects one side of the body.

  • Most cases are due to severe mutations in the SCN1A gene.
  • Most children progress varying degrees of developmental disability.
  • Treatment involves finding the best combination of medications to treat seizures and prevent seizure emergencies. Diet therapy and vagus nerve stimulation can also be helpful.
  • The FDA approved two new drugs specifically for dravet syndrome. These include Epidiolex (cannabadiol, CBD) oral explanation approved in June 2018 and Stiripentol approved in August 2018. Fenfluramine (Fintepla) was approved in June 2020.
  • A multidisciplinary team and a primary developmental calculation are needed to address the many ways that Dravet syndrome can affect a child and their family.

Alternate name

Dravet syndrome, before known as severe myoclonic epilepsy of infancy (SMEI)

Types of dravet syndrome

Dravet syndrome is an unadorned form of epilepsy characterized by prolonged seizures that usually appear in the first year of life. As the disease develops, different types of seizures start to occur.

Seizures are classified into three main types depending on the part of the brain they affect: focal onset or partial seizures, widespread seizures, and unknown onset seizures. Focal start seizures start on one side of the brain while widespread seizures affect both sides of the brain simultaneously. In unknown onset seizures, the location in the brain where the seizure starts are not known.

Seizures also may be secret based on their cause such as, for instance, febrile seizures, or seizures caused by high temperature, as well as symptoms they cause, myoclonic seizures, clonic seizures, tonic seizures, tonic-clonic seizures, absence seizures, atonic seizures, principal impaired-awareness seizures.

Febrile seizures

Febrile seizures usually are generalized seizures. They are a convulsion activated by a fever that often accompanies childhood illnesses. In children with dravet syndrome, they typically occur within the first year after birth and often are much more severe than those seen in children with other diseases.

Most febrile seizures are brief and do not typically cause long-term health problems. However, repetitive prolonged febrile seizures increase children’s risk of emerging epilepsy and are the first sign that a child may have dravet syndrome.

Myoclonic seizures

Myoclonic seizures are another type of generalized seizure. This type of seizure causes children’s muscles to rapidly agree and relax, resulting in jerky movements. In children with dravet syndrome and other epilepsy disorders, these jerking movements happen on both sides of the body. These seizures usually do not affect the child’s consciousness, leave-taking them aware and able to think during the episode. When these seizures are current in children with dravet syndrome they usually occur by the age of two.

Clonic seizures

Clonic seizures can be either focal onset or widespread onset in origin. This type of seizure causes jerky movements in which the person’s muscles stiffen and relax. It often is difficult to differentiate a myoclonic seizure from a clonic seizure, but clonic seizures usually involve a more rhythmic jerky movement. This type of seizure most commonly occurs in babies and may last from a few seconds to one minute. These seizures cannot be stationary by restraining the child.

Tonic seizures

Tonic seizures can be also focal onset or generalized onset in origin. This type of seizure causes a person’s body to develop unexpectedly stiff. They usually happen while the person is sleeping and last less than 60 seconds. A person experiencing a tonic seizure may be completely aware of the episode or their awareness may be slightly impaired. They may feel tired or disordered after the event and have a headache. Tonic seizures are very rare in dravet syndrome.

Tonic-clonic seizures

Tonic-clonic seizures usually are widespread onset, but also can be focal onset. This type of seizure involves a combination of symptoms from tonic and clonic seizures. The tonic stage of the convulsion begins first with the person’s body abruptly becoming stiff, followed by the clonic phase in which the person’s body jerks rhythmically. These seizures typically last one to three minutes. Toward the end of the seizure, the jerky actions slow to a stop and the person’s body relaxes. During this time, the person may lose the switch of the bladder or bowels. A tonic-clonic seizure permanent for more than five minutes requires immediate medical help.

Absence seizures

Absence seizures are a type of generalized onset seizure. This kind of seizure causes children to have lapses of consciousness where they have no recollection of the incident afterward. These seizures are abrupt and previous only a few seconds. They are considered by non-motor symptoms, although brief twitches may be present. A common symptom of this type of seizure is blank staring that is often mistaken for daydreaming. Once diagnosed, absence seizures can be controlled with anti-seizure medications. It is possible for children to enlarge absence seizures and this commonly happens in their teenage years.

Children with dravet syndrome also can have an additional type of absence seizure known as atypical absenteeism seizure. These seizures also are a kind of generalized onset seizures and usually happen after age two. Unlike regular absence seizures, children experiencing atypical absence seizures may be able to respond to external stimuli.

Atonic seizures

Atonic seizures can be focal onset or generalized onset. These seizures are also known as falling attacks because there is a loss of muscle control that results in flabby muscles. They usually last less than 15 seconds. They do not cause direct damage but can cause indirect injuries from falls. Head protection is often recommended for children with these types of seizures.

Focal seizures of altered consciousness

Focal deficient consciousness seizures usually occur after the age of two years and generally lasts one to two minutes. They originate on one side of the brain. The patient loses consciousness, so the main symptoms are lack of response and confusion. In addition, children can have automaticities such as lip-smacking or clumsiness.

Status epilepticus

Status epilepticus can occur in children with dravet syndrome. This is when a seizure lasts more than five minutes or when several seizures occur together with no recovery time in between. There are two types of rank epilepticus: convulsive and non-convulsive. Convulsive status epilepticus usually results from a prolonged tonic-clonic seizure. This type needs emergency medical treatment because it is life-threatening. Non-convulsive status epilepticus is usually caused by the prolonged absence or by seizures of focal altered consciousness. These seizures are harder to recognize because the symptoms are subtler.

What causes dravet syndrome?

Dravet syndrome is a genetic condition. In 80 percent of Dravet patients, the disease is caused by changes in the SCN1A gene. The remaining 20% of cases are believed to be the result of mutations in other genes, some of which have yet to be identified.

Most disease-causing mutations occur de novo, which means they are new and are not passed down from parents. But up to 10% of the time, mutations that cause dravet syndrome are inborn from parents in an autosomal dominant manner, meaning that just one defective copy of the disease-causing gene is enough for the condition to develop.

Dravet syndrome risk factors

As children with dravet syndrome grow older, their decline in cognitive function stabilizes. The degree of intellectual disability varies widely from mild to profound, however, most adolescents and adults with dravet syndrome are dependent on caregivers. Gait abnormalities appear to worsen during adolescence. Seizures tend to decrease in amount and duration with age. People with dravet syndrome are at higher risk than the general population for a sudden and unexpected death, but that risk remains low.

Dravet syndrome symptoms

The following list includes the most mutual signs and symptoms in persons with dravet syndrome. These characteristics can vary from one person to another. Some persons may have more symptoms than others, and symptoms can range from slight to severe. This list does not include all the symptoms or characteristics that have been described in this condition.

Signs and symptoms include:

  • Many different types of seizures.
  • Sudden muscle jerks (myoclonus)
  • Loss of developmental skills.
  • Intellectual disability
  • Trouble walking
  • Speech disability
  • Autistic-like behavior

The first seizures appear before one year of age and are often associated with fevers. In childhood, other types of seizures develop, and the incidence of seizures increases. Loss of cognitive and developmental skills can occur along with speech problems and difficulty walking. In adulthood, the number of seizures may decrease and nocturnal seizures may occur. More serious complications include the risk of ongoing seizures (status epilepticus) and sudden unexplained death.

This table lists the symptoms that people with this disease may have. For most diseases, symptoms vary from person to person. People with the same disease may not have all of the listed symptoms. This information originates from a database called Human Phenotype Ontology (HPO). The HPO collects information around symptoms that have been labeled in medical resources. The HPO is periodically updated. Use the HPO ID to access more detailed information about a symptom.

Dravet syndrome diagnosis

Dravet syndrome is a clinical diagnosis that was recently determined to affect 1: 15,700 babies born in the US. Approximately 80% of those diagnosed with dravet syndrome have an SCN1A change (1: 20,900), but the attendance of a mutation alone is not sufficient for the diagnosis, nor does the absence of a mutation exclude the diagnosis. Dravet syndrome is at the more severe end of the spectrum of SCN1A-related disorders, but it can also be associated with other mutations.

In the 2015 study, the clinical diagnostic criteria included at least 4 of the following:

  • Normal or near-normal cognitive and motor development before the onset of seizures
  • Two or more seizures with or without fever before one year of age
  • History of seizures consisting of generalized myoclonic, hemiclonic, or tonic-clonic seizures
  • Two or more seizures lasting more than 10 minutes
  • Lack of response to first-line antiepileptic drug therapy with continuous seizures after 2 years of age

Other hallmarks of the syndrome include seizures associated with vaccinations, hot baths, or warm temperatures; developmental slowdown, stagnation or regression after the first year of life; behavior problems; and speech delay.

Genetic test

Because many of these criteria are not apparent in the first year of life, and babies with dravet syndrome initially experience typical development, the study determined that genetic testing through an epilepsy panel should be considered in patients with either of the following:

  • 2 or more prolonged seizures per year of age
  • 1 prolonged seizure and any hemiclonic seizure (sustained rhythmic jerking of one side of the body) at 1 year of age
  • 2 seizures of any duration that appear to affect alternate sides of the body
  • History of seizures before 18 months of age and subsequent onset of myoclonic and/or absence seizures

If you suspect that your loved one might have dravet syndrome, ask your neurologist about the tests, which are available finished by your doctor or commercially. An epilepsy panel will test for SCN1A, as well as many other genes commonly related to epilepsy. After testing, it is optional to consult with a genetic counselor.

Dravet syndrome treatment options

Seizures in dravet syndrome can be difficult to control but can be reduced with anti-seizure medications such as clobazam, stiripentol, topiramate, and valproate. Because the course of the disorder varies from one individual to another, treatment protocols may vary. A high-fat, low carbohydrate diet can also be beneficial, known as a ketogenic diet. Although adjusting your diet can help, it does not eliminate symptoms. Until a better form of treatment or cure is discovered, people with this disease will have myoclonic epilepsy for the rest of their lives.

It is now known that certain anti-seizure medications that are classified as sodium channel blockers make seizures worse in most dravet patients. These medications include carbamazepine, gabapentin, lamotrigine, and phenytoin. Treatments include cognitive rehabilitation through psychomotor and speech therapy. In addition, valproate is often given to prevent the recurrence of febrile seizures, and benzodiazepine is used for long-lasting seizures, but these treatments are often insufficient.

Stiripentol was the only drug for which a randomized, double-blind, placebo-controlled trial was conducted, and this drug showed efficacy in trials. It acts as a GABAergic agent and as a positive allosteric modulator of the GABAA receptor. Stiripentol, which can improve refractory focal epilepsy as well as dravet syndrome, supplemented with clobazam and valproate, was approved in Europe in 2007 as a therapy for dravet syndrome and has been found to reduce the overall rate of seizures by 70%. For more drug-resistant seizures, topiramate and the ketogenic diet are used as alternative treatments.

Cannabidiol (CBD) was approved in the United States for the treatment of dravet syndrome in 2018. A 2017 study showed that the frequency of seizures per month decreased from 12 to 6 with the use of cannabidiol, compared to a decrease from 15 to 14 with placebo.

Dravet syndrome complications

  • Although the decline in cognitive function stabilizes with age in some people with dravet syndrome, most adolescents and adults with the disorder have mild to profound intellectual disability and require 24-hour supervision. This disability, along with seizures and other comorbidities, can also cause severe anxiety and social isolation, which inevitably affects the quality of life of caregivers as well.
  • Gait and balance problems associated with dravet syndrome can lead to falls. These falls, along with an increased risk of osteopenia (low bone mass), can cause bones to break. A survey study found that 70 percent of respondents use a wheelchair or adaptive stroller sometimes.
  • Seizures can cause drowning if they occur while a person is in or near water. Seizures can also increase the risk of lung complications, such as aspiration pneumonia, which occurs when you breathe in food, stomach acid, or saliva into your lungs, which can lead to sepsis.