What is Dravet Syndrome?

From the Epilepsy foundation:

  • Dravet syndrome is a rare genetic dysfunction of the brain.
  • It begins in the first year of life in an otherwise healthy infant and is lifelong.
  • Most children develop some developmental disability.
  • Treatment involves finding the best combination of medicines to treat seizures and prevent seizure emergencies. Dietary therapy and vagus nerve stimulation can also be helpful.
  • Epidiolex (cannabadiol, CBD) oral solution, approved by the FDA in June 2018, was the first medicine approved specifically for Dravet Syndrome.
  • A multidisciplinary team and early developmental assessment are needed to address the many ways Dravet syndrome can affect a child and their family.

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:

  • Infants have normal development at the time the seizures begin. Yet as seizures continue, most children develop some level of developmental disability and other conditions associated with the syndrome.
  • It is commonly misdiagnosed. MRI (magnetic resonance imaging) and EEG (electroencephalogram)tests are also normal in infants at first.
  • About 8 out of 10 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.

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 (once referred to as a grand mal seizure) or a seizure involving clonic (jerking) movements on one side of the body.
  • Myoclonic seizures (brief shock-like jerks of a muscle or group of muscles) appear between 1 and 5 years in 85% of children with Dravet syndrome.
  • Seizures early in life are often long (lasting more than 2 minutes) or repetitive and can result in status epilepticus, a life-threatening condition.
  • Children with Dravet syndrome can develop many different seizure types:
  • After the first febrile seizure, seizures can happen 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 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 start improving. Yet most children with Dravet syndrome have some degree of developmental disability that persists.
  • Other problems that may be seen include:
    • Low motor tone that can lead to painful foot problems
    • Unsteady walking
    • Older children and adults may develop a crouched gait
    • Chronic infections
    • Low humoral immunity (meaning their body has less ability to create antibodies to fight infection)
    • Growth and nutritional problems
    • Problems with the autonomic nervous system

Who gets it?

  • It’s not fully known how many people are affected. Reports suggest that 1 in 20,000 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.
  • 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 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 people with Dravet syndrome.
  • Surgery is not indicated in most people with Dravet syndrome.
  • Vagus nerve stimulation (VNS) may be useful in some children.
  • A purified form of cannabidiol (CBD, a part of the cannabis plant), called Epidiolex, was approbed by the FDA for use in Dravet Syndrome in June 2018.
  • 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. People with Dravet syndrome should receive physical, occupational, speech, and social/play therapies, and an enriched environment is encouraged.