Dravet Syndrome

Dravet syndrome is an uncommon genetic neurodevelopmental disorder starting in infancy and marked by multiple seizure types which may include deadly chronic seizures that need emergency medical care. The condition was first reported in 1978 by Dr. Charlotte Dravet, a French doctor. It is also known by other names, including PMEI/    polymorphic epilepsy in infancy, SMEI/severe myoclonic epilepsy in infancy, and epilepsy with polymorphic seizures.

 

The course of Dravet syndrome varies from one affected individual to another and is marked by characteristic symptoms such as varied treatment-resistant seizure types, reduced immunity, developmental delays, hyperactivity, and orthopedic problems. Patients are also at increased risk to sudden unexplained death in epilepsy/SUDEP and related ailments which also require management and treatment. A few common related conditions include sensory integration deficits; balance and movement problems; behavioral, speech, and language delays; sleeping problem, nutrition and growth abnormalities; persistent infections; and disturbances in the autonomic nervous system, which among other things also controls sweating, body temperature, and other bodily functions.

Most patients tend to have a family history of seizure disorders or febrile seizures. The incidence rate Dravet syndrome ranges between 1 in 20,000 to 40,000 births; it may turn out to be greater with better diagnostic methods and discover of new genetic proof. In single figures, the incidence rate is denoted as 1 in every 30,000 births.

 

Symptoms of Dravet syndrome

 

The signs and symptoms of Dravet syndrome occurs in the below listed manner:

• The first convulsion or seizure occurs during the first year of an otherwise healthy newborn with normal neuro-development. It may occur along with fever and tends to be prolonged, often lasting for more than 5 minutes. The seizures may be one-sided or affect the whole body and need emergency care. With the passage of time, the incidence of fits increase, often without fever.
• In the second year through to the 4^thyear of life, additional forms of seizures like single jerks/myoclonic fits and unresponsiveness and staring/atypical absence or focal seizures may occur. They may be difficult to treat, with drugs, alternative medicines, etc., although diet changes may alleviate symptoms.
  • Developmental delays as well as sleep disturbances, imbalance, and behavioral problems, etc., may become noticeable. Myoclonic seizures tend to diminish with time, but convulsive seizures usually continue; they often occur during sleep and may be accompanied by illness or fever.
  • There is stabilization of cognitive, motor, and communication problems, but delays are still substantial and evident.
  • Dravet syndrome affected children are also prone to SUDEP as compared to other types of epilepsy. However the chances of survival into adulthood is over 80 percent.

Some of the hallmark symptoms of Dravet syndrome are as follows:

• Commencement of different types of seizures during the first year of life.
• Seizures commence as febrile, but can later occur without fever
• Bouts of prolonged seizures
• Seizures remain unresponsive to normal anti-seizure medications or anticonvulsants
• Development is normal at first, but slows down significantly in the second year. It is marked by weak motor skills, hyperactivity, poor development of language, and mental retardation, etc.
• Myoclonic seizures commence after 18 months
• Some seizures can be linked to hot baths, vaccinations, and/or warm environments
• With age, there is stabilization of cognitive function decline and improvement is seizures. Teens with Dravet syndrome are however dependent on others and may remain so for the rest of their lives.
• Additional disorders associated with SUDEP also need to be treated.

 

Causes of Dravet syndrome

 

Nearly 80 percent of Dravet syndrome cases are caused due to mutations in the SCN1A gene. Research is till on to find out the associated genetic mutations and other causes of Dravet syndrome in patients with nil errors of the SCN1A gene.

It may be noted that the SCN1A gene is responsible for manufacturing certain proteins that help control the functions of sodium ion channels. Any kind or error, change, or mutation in this gene can thus result in dysfunction of the sodium ion channels present in the brain. Such malfunction is considered to cause the characteristic seizures and associated neurodevelopmental problems.

Healthy individuals contain 2 copies of the SCN1A gene on the 2 copies of chromosome 2. The mutation associated with Dravet syndrome is characterized by inactivation of one of the copies of the SCN1A gene.  The presence of just one active SCN1A gene cannot efficiently regulate the sodium ion channels, thereby resulting in the seizures. Another important point to remember is the fact that not all kinds of SCN1A gene mutations eventually cause Dravet syndrome; it may however be responsible for the development of other forms of epilepsy.

Most instances of SCN1A gene mutations associated with Dravet syndrome occur at random and are completely new to the patient. However, many patients have also been found to have a family history of some kind of epilepsy or febrile seizures. It is very rare for the genetic mutation to be directly passed on by one of the parents to the child.

The subdivisions of Dravet syndrome are listed below:

• Febrile seizures
• ICE-GTC
• EMRF, i.e., epilepsy with mental retardation limited to females
• GEFS+ i.e., genetic epilepsy with febrile seizures plus
• SMEB, i.e., severe myoclonic epilepsy borderline

Treatment of Dravet syndrome

Dravet syndrome has no standard treatment option as the symptoms and course of the disorder tends to vary from one affected child to another.

• In most cases, antiepileptic drugs such as valproic acid, clobazam, topiramate, sodium valproate, stiripentol, and levetiracetam, are usually prescribed by doctors to treat the seizures. The response to these medications is variable and seizures may continue in most instances.
• It is important to avoid contraindicated medications such as carbamazepine, lamotrigine, etc., as they can increase the frequency of seizures and aggravate Dravet syndrome.
• Prolonged seizures need emergency care. Hence, doctors may prescribe rescue medicines like benzodiazepine, to manage the seizures on a temporary basis.
• Associated secondary conditions such as growth and nutrition, orthopedic ailments, etc., also need to be managed. Behavioral, social, language, and mental problems can be managed via varied therapies.
• It is important to learn about all the triggers of seizures, such as hot weather, stress, bright lights, etc., and avoid them. Use of cooling vests, protective helmets, seizure alarms, pulse oximeters, and photosensitive glasses can help in daily management of seizures.
• Alternative treatments include a ketogenic diet marked by low carbohydrates and high fat content and VNS/vagal nerve stimulation.

 

Dravet syndrome life expectancy

 

Dravet syndrome patients tend to have a much lower than normal life expectancy. They may require medical care for the rest of their lives. Effective management of the condition can prolong their life expectancy. The average life expectancy of a Dravet Syndrome child is seven or eight years.