What is Dravet Syndrome?

Dravet syndrome, also known as Severe Myoclonic Epilepsy of Infancy (SMEI), is a rare and catastrophic form of intractable epilepsy that begins in infancy. Initial seizures are most often prolonged events and in the second year of life other seizure types begin to emerge. Development remains on track initially, with plateaus and a progressive decline typically beginning in the second year of life. Individuals with Dravet syndrome face a higher incidence of SUDEP (sudden unexplained death in epilepsy) and have associated conditions, which also need to be properly treated and managed. These conditions include:

o o o o o o o o o

behavioral and developmental delays movement and balance issues orthopedic conditions delayed language and speech issues growth and nutrition issues sleeping difficulties chronic infections sensory integration disorders disruptions of the autonomic nervous system (which regulates things such as body temperature and sweating)

Children with Dravet syndrome do not outgrow this condition and it affects every aspect of their daily lives.

Unless a cure or better treatments for Dravet syndrome and related epilepsies are found, individuals with these disorders face a diminished quality of life. Current treatment options are extremely limited and the prognosis for these children is poor. The constant care and supervision of an individual with such highly specialized needs is emotionally and financially draining on the family members who care for these individuals.

We invite you to watch the video Ciaras Light by Paulo Caserta Films. This 10-minute documentary about the ODriscoll family and their daughters journey with Dravet syndrome gives you a perspective of what it is like to live with this disease.

Real Stories

Learn About Diagnosis & Treatment

Related Epilepsies
SCN1A-related seizure disorders encompass a spectrum that ranges from simple febrile seizures (FS) and generalized epilepsy with febrile seizures plus (GEFS+) at the mild end to Dravet syndrome and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC) at the severe end.[1] These epilepsy syndromes include:

o o o o o o o o

Febrile Seizures (FS) Generalized Epilepsy with febrile seizures plus (GEFS+) Severe Infantile Multifocal Epilepsy (SIMFE) Severe Myoclonic Epilepsy of Infancy Borderline (SMEB) Severe Myoclonic Epilepsy of Infancy (SMEI/Dravet Syndrome) Epilepsy and mental retardation limited to females (EFMR/PCDH19) Sporadic Infantile Epileptic Encephalopathy (SIEE) Intractable Childhood Epilepsy with Generalized Tonic Clonic Seizures (ICEGTC)

General Discussion
Dravet syndrome is a rare genetic epileptic encephalopathy (dysfunction of the brain) with onset during the first year in an otherwise healthy infant. Mutations of the SCN1A gene cause 79% of diagnosed cases of Dravet syndrome. Frequently referred to as a sodium channelopathy, this intractable epilepsy is characterized by unilateral (one-sided) clonic or tonic clonic (grand mal) seizures that are prolonged (> 5 minutes) or progress to status epilepticus (>30 minutes) and require emergency management. Myoclonic seizures, often called myoclonic jerks, are common. Over time seizures present without fever, illness or heat triggers. Seizures are frequent and resistant to treatment. The first seizure is often associated vaccine administration at six months of age. Between one and four years of age, children develop other seizure types including atypical absence, eyelid myoclonia and non-convulsive seizures. All seizure types may be prolonged or lead to status epilepticus. Seizures are intractable (uncontrollable) and combination drug therapy is necessary for acceptable seizure control. Some anti-epileptic drugs exacerbate seizures and should be avoided. In most cases, surgery is not indicated. The initial EEG is normal but within the second or third year of life, brief generalized spike, polyspike, or polyspike-wave paroxysms appear. MRI and metabolic studies are normal. Developmental delays appear to varying degrees in most patients by age two years and ataxia (abnormal gait) is common. Confirmation of diagnosis by genetic testing, appropriate and aggressive seizure management, and implementation of global therapies are necessary to improve the outcome of children affected with Dravet syndrome.

Generalized epilepsy with febrile seizures plus (GEFS+) or Dravet syndrome is a syndromic autosomal dominant disorder where afflicted individuals can exhibit numerous epilepsy phenotypes.[1] GEFS+ can persist beyond early childhood (i.e., 6 years of age). GEFS+ is also now believed to encompass three other epilepsy disorders: severe myoclonic epilepsy of infancy (SMEI), which is also known as Dravet's syndrome, borderline SMEI (SMEB), and intractable epilepsy of childhood (IEC).[2][3] There are at least six types of GEFS+, delineated by their causative gene. Known causative genes are the sodium channel subunit genes SCN1A, an associated subunit SCN1B, and a GABAA receptor subunit gene, GABRG2 and there is another gene related with calcium channel the PCDH19 which is also known as Epilepsy Female with Mental Retardation.[4] Penetrance for this disorder is estimated at approximately 60%.[5]

What is SMEI or Dravet syndrome?

Dr. Charlotte Dravet first described Dravet syndrome in 1978 as Severe Myoclonic Epilepsy of Infancy (SMEI). Dravet syndrome is at the most severe end of the Dravet Spectrum Disorders. The key features of Dravet syndrome are febrile seizures and status epilepticus. The first seizures usually happen before one year of age, with no known cause other than fever or illness. Seizures that are brought on by fever are called febrile seizures. The first seizure may be a tonic clonic seizure or hemiclonic seizure. Tonic clonic seizures involve a stiffening of the arms and legs (tonic phase) and jerking of the arms, legs, and head (clonic phase). Tonic clonic seizures are also called grand mal. Hemiclonic seizures are similar to tonic clonic seizures, though only one side of the body is convulsive. Seizures progress to be frequent and intractable in SMEI, meaning that seizures do not respond well to treatment. They also tend to be prolonged, lasting more than 5 minutes. Prolonged seizures may lead to status epilepticus, a medical emergency. Status epilepticus is defined as a seizure that lasts more than 30 minutes, or seizures that occur in clusters, one after another. Seizures usually become afebrile, which means they occur spontaneously without fever. Other types of seizures appear in early childhood, including myoclonic seizures, atypical absence and complex partial seizures. Nocturnal seizures, or seizures that occur at night, are common in Dravet syndrome. What is SMEB? Severe myoclonic epilepsy borderline (SMEB) is a term that is used to describe a subset of Dravet syndrome patients having less severe symptoms and moderate, rather than severe, developmental delays. Myoclonic seizures are not typical in SMEB. Children with Dravet Syndrome are likely to develop other complications. Developmental delays appear between two and four years of age. This may or may not include regression or loss of developmentally attained skills. Children may be delayed or impaired in speech, exhibit autisticlike behaviors, or lose their ability to control movement (ataxia). Children may have difficulty

sleeping, be prone to infection, or become sensitive to temperatures, visual patterns, and environmental lighting. The absence of disease complications should not delay genetic testing when prolonged febrile seizures occur in infancy. The degree to which complications are seen in Dravet syndrome is much more variable than when the disease was first described. Most, but not all, patients with Dravet syndrome test positive for SCN1A gene mutations. Patients who do not have a positive result for a SCN1A mutation may have a mutation in part of the SCN1A gene that is not examined for mutations in standard tests. All types of SCN1A mutations are seen in Dravet syndrome. These include missense, nonsense, frameshift, insertion, deletion, and duplication. Mutations of SCN9A, SCN2B, PCDH19 and GABRG2 genes are also seen rarely in those diagnosed with Dravet syndrome. Approximately three out of ten Dravet patients have no detectable genetic mutation. It is expected that more precise genetic testing in the future will find genetic mutations in these patients.

Dravet syndrome
What is a syndrome?

A syndrome is a group of signs and symptoms that, added together, suggest a particular medical condition. In epilepsy, examples of these signs and symptoms would be things like the age at which seizures begin, the type of seizures, whether the child is male or female and whether they have physical or learning disabilities, or both. The results of an electroencephalogram (EEG) are also used to help identify epilepsy syndromes. Epilepsy Action has more information about seizure types, learning disabilities, and the EEG. If you would like to know more about an epilepsy syndrome, please speak to your doctor. If you would like to know more about epilepsy in general, please contact Epilepsy Action. Other names for Dravet syndrome Severe myoclonic epilepsy in infancy (SMEI)
Dravet syndrome

Dravet syndrome is a very rare form of childhood epilepsy. Out of 500 children with epilepsy, only one, or at most two, children are likely to have this form of epilepsy. The epilepsy usually starts with seizures that may seem to be very similar to febrile convulsions. The more typical features of Dravet syndrome usually become more obvious during the second year of life.

Epilepsy Action has more information about febrile convulsions.

Symptoms

The seizures begin in the first year of life. They are most often associated with a high temperature (febrile convulsion). They often involve just one side of the body, although both sides of the body may be involved. The seizures are characterised by stiffness and jerking (called a tonic-clonic seizure), or just repeated jerking (called a clonic seizure). Febrile convulsions in Dravet syndrome are usually quite long, sometimes lasting for 15 or 30 minutes, or even longer. They often happen repeatedly in the first year of life. However, at this time it can be difficult to differentiate these children from others with briefer febrile convulsions, who do not go on and develop other types of seizure. During the second year of life the seizures become more frequent and persistent, and are often more obviously focal (also called partial) involving one part of the body. They may happen with or without a fever, and at any time of day and night. In addition to the tonic-clonic seizures, myoclonic seizures (myo meaning muscle, and clonus meaning jerk) and focal seizures become common. Often the children are photosensitive (have seizures brought on by flashing or flickering lights). Seizures may also sometimes be brought on by hot environments or hot showers or baths. The early development of children with Dravet syndrome is usually normal. However, the childs development starts to slow down and children may lose skills towards the end of the second year of life. The childs speech and language is particularly affected. Epilepsy Action has more information on generalised seizures, focal seizures and photosensitive epilepsy.
Diagnosis

A full history and description of the seizures that have happened in the past and at the time the child attends their hospital appointment is very important. It is also important for parents to give the doctor a detailed account of their childs development. The EEG, which records the electrical activity in the brain, is usually normal early on in this condition. By the time the child is 18 months old, the EEG shows evidence of epileptic activity, with spike and wave or polyspike discharges. These happen either as a single event, or in bursts. They may be generalised involving the whole brain, or happening just from one small area of the brain. Some, but not all, children with Dravet syndrome show EEG evidence of sensitivity to flashing or flickering lights, called photosensitivity. Brain scans in children with Dravet syndrome are usually normal. Recently a specific genetic abnormality, called a mutation has been found in at least eight out of 10 children with Dravet syndrome. This mutation is known as the SCN1A mutation. The mutation can be looked for in a simple blood test. The discovery of this mutation has been very helpful in making or confirming a diagnosis of this epilepsy syndrome.

Epilepsy Action has more information on diagnosing epilepsy, the EEG and photosensitive epilepsy.
Treatment

Dravet syndrome is one of the epilepsy syndromes that are most resistant to epilepsy medicines. Sodium valproate (Epilim) and lamotrigine (Lamictal) are usually tried first. However, lamotrigine makes the myoclonic seizures worse in many children. Other medicines which are helpful include clobazam (Frisium) and stiripentol (Diacomit). Many children with Dravet syndrome seem to respond best to a specific combination of sodium valproate, stiripentol and clobazam. It is very important that only specialist epilepsy doctors, called paediatric neurologists, prescribe this combination of medicines. Other treatments which might be helpful include topiramate (Topamax), clonazepam (Rivotril) and zonisamide (Zonegram). A short course of a steroid (called prednisolone) and the ketogenic diet may also be helpful. Children with Dravet syndrome may have seizures that go on for a long time and where an ambulance should be called. The children will need to be prescribed emergency or rescue medicine to be given at home before the ambulance arrives. Because children with Dravet syndrome always have learning disabilities they will also need full educational assessment and support. Epilepsy Action has more information on treatment, epilepsy medicines, the ketogenic diet, and learning disabilities.
Prognosis (outlook)

The seizures continue to be very difficult to control, throughout childhood. Learning disabilities persist and are usually severe. As the condition progresses most children become unsteady on their feet (ataxic). Children with Dravet syndrome will need to be cared for throughout their lives. Usually by the age of 14 or 16 years, the seizures tend to become less frequent.

Visiting your GP (family doctor)

If you think that youve had a seizure, the first person to see is your GP. If your GP thinks you might have epilepsy, they will usually arrange for you to see an epilepsy specialist at the hospital. This is to make sure you get the right diagnosis and have the best treatment for your epilepsy. The epilepsy specialist is usually a neurologist (for adults) or a paediatrician (for children).

Epilepsy clinics

If there is an epilepsy clinic in your area, your GP will usually refer you there. Epilepsy clinics provide things like fast-track appointments for people who have had their first seizure, and the latest scanning equipment.

Introduction
Like many people with epilepsy and their families, you may have concerns about safety in relation to seizures. In these web pages we look at some aspects of everyday life, where there could be a risk of injury during a seizure. We also make suggestions on how to reduce risk. Its important to remember that our safety suggestions are not right for everyone. So some things may not be relevant or necessary for you. For example, if you are seizure-free, you may only need to take the same precautions as someone without epilepsy. If you get a useful warning of your seizures, you may be able to reduce risk of injury by stopping what youre doing. However, if you have fairly frequent seizures without warning, you may need to take extra care.

Dr. Charlotte Dravets' Publication

Dravet's Syndrome (severe myoclonic epilepsy in infancy)
By Charlotte Dravet
Date of submission: August 16, 1993 Date of update: August, 1999 Date of update: March 2003 Medline SEARCH DATE: March 2003