What is Dravet Syndrome?

Dravet Syndrome is a rare genetic epileptic encephalopathy  (dysfunction of the brain). It begins in the first year of life in an otherwise healthy infant. Prior to 1989, this syndrome was known as epilepsy with polymorphic seizures, polymorphic epilepsy in infancy (PMEI) or severe myoclonic epilepsy in infancy (SMEI). The disease begins in infancy but is lifelong.  Some more important points:

  • About 80% of people with this syndrome have a gene mutation that causes problems in the way that ion channels in the brain work. This mutation is most often not inherited from the parents, but is considered a de novo or "new" mutation in the child. The seizures are refractory, or do not respond to seizure medications well in most cases.
  • Most children develop some level of developmental disability and have other conditions that are associated with the syndrome.
  • It is commonly misdiagnosed.
  • Infants have normal development at the time the seizures begin.  MRI and EEG tests are also normal in infancy. 

What is it like?

  • Seizures generally start within the first year of life. The first seizure is often associated with a fever and may be a tonic clonic seizure (commonly referred to as a grand mal seizure) or a seizure involving clonic (jerking) movements on one side of the body.
  • Myoclonic seizures appear between 1 and 5 years in 85% of children with Dravet Syndrome.
  • Seizures early in life are often prolonged (lasting more than 2 minutes) or repetitive and can result in status epilepticus, a life threatening condition in which seizures last longer than 30 minutes.
  • Children with Dravet syndrome can develop many different seizure types:
    • Myoclonic seizures
    • Tonic clonic seizures
    • Absence seizures
    • Atypical absence seizures 
    • Atonic seizures
    • Partial seizures
    • Non-convulsive status epilepticus
  • Seizures occur without a fever. However, these children are very sensitive to infections and frequently have seizures when they are ill or have a fever.
  • Seizures can also be triggered by slight changes in body temperature that are not caused by infection for example a warm or hot bath water or hot weather.
  • Many children have photosensitive seizures triggered by flashing lights, patterns or similar photic triggers.
  • Emotional stress or excitement can also trigger seizures in some children.
  • Children usually develop normally in the early years. After age 2, they may lose developmental milestones or do not progress as quickly as they get older and have more seizures.
  • There seems to be a correlation between frequency of seizures, how often status epilepticus occurs, and the degree of developmental delay in children.
  • Around 6 years old, cognitive problems in some children may stabilize or may start improving. However, most children with Dravet syndrome have some degree of developmental disability that persists.
  • Other problems that may be seen include:
    • Low motor tone – can lead to painful foot problems
    • Unsteady walking
    • Older children and adults may develop a crouched gait
    • Chronic infections
    • Low humoral immunity
    • Growth and nutrition problems
    • Problems with the autonomic nervous system
    • Behavioral or developmental problems such as autism spectrum disorder

 Who gets it?

  • It’s not fully known how many people are affected. Reports suggest that 1 in 20 to 1 in 40,000 people have Dravet Syndrome. Three to 8% of children who have their first seizure by 12 months old may have Dravet Syndrome.
  • Seizures lasting more than 10 minutes, seizures occurring on one side of the body, and seizures triggered by a warm water bath in children under 12 months old are considered significant risk factors for a Dravet Syndrome diagnosis.

Tell me more

  • The most common gene mutation linked to Dravet Syndrome is in a gene called SCN1A. When this gene isn’t working properly, sodium channels in the brain (which help brain cells function) do not work correctly.
  • Many other gene mutations can affect sodium channels and cause Dravet Syndrome too.
  • A blood test for the mutation can confirm the diagnosis. Sometimes a gene mutation is not found on testing but the syndrome may be diagnosed based on symptoms.
  • Although the first seizure in infants with Dravet syndrome may be near the time of a vaccine, vaccines do not cause Dravet Syndrome. Children should get recommended immunizations.

How is it treated?

  • Diagnosing the child early is critical to proper treatment and achieving the best outcome.
  • A multidisciplinary team is needed to address the many ways that Dravet Syndrome can affect a child and their family.
  • Seizure treatment is aimed at finding the best combination of medicines to treat seizures chronically and prevent and treat potential seizure emergencies.
  • Getting the best seizure control possible is the goal. This could also help improve the child’s developmental abilities and decrease mortality risk.
  • Usually 2 or more seizure medications are needed to treat the multiple seizure types.
  • It’s important to avoid medications called sodium channel blockers as these can worsen seizures in Dravet Syndrome. This includes phenytoin (Dilantin), fosphenytoin (Cerebyx, Prodilantin), carbamazepine (Tegretol), oxcarbazapine (Trileptal), lamotrigine (Lamictal) and rufinamide (Banzel) .  Additionally the medications vigabatrin (Sabril), and tiagabine (Gabatril) may increase the frequency of myoclonic seizures and should be avoided. 
  • The ketogenic diet has been helpful in some patients with Dravet syndrome.
  • Surgery is not indicated in most patients with Dravet syndrome.
  • Vagal Nerve Stimulator (VNS) may be useful in some patients.
  • Seizure Response Plans should include how to treat children when they have a fever or illness, use of seizure monitors and alerts, as well as emergency management of prolonged or repeated seizures.
  • Developmental assessments should begin as early as possible. Persons with Dravet syndrome should receive physical, occupational, speech, and social/play therapies and an enriched environment is encouraged.
     

What's the outlook?

  • Seizures are refractory to medications. This means that medical treatment is very complicated. Currently available medications are not able to achieve complete seizure control.
  • Other health problems need to be identified and treated early. These also affect a child’s development and outlook for the future.
  • People with epilepsy that is difficult to treat, who have tonic clonic seizures, who are on multiple seizure medicines, and who have developmental delays have a higher risk of Sudden Unexplained Death in Epilepsy (SUDEP).  Other causes of mortality associated with Dravet syndrome include consequences of status epilepticus and accidental death from injury or drowning.
  • While the diagnosis and consequences of Dravet Syndrome can be catastrophic, the cause is known. Ideally, more research can be targeted to improve treatment and find a cure.

 

For more information:

 

Special thanks to Michelle Welborn PharmD of ICE Epilepsy Alliance

Authored by: Joseph I. Sirven MD / Patricia O. Shafer RN MN on 3/2014
Reviewed by: Patricia Dean ARNP MSN/ Michelle Welborn PharmD on 3/2014
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