Genetics of Dravet Syndrome
Dravet Syndrome is one of the most common genetic epilepsies to occur in early childhood.
Dravet Syndrome is a clinical diagnosis, based on recognition of seizure types, the clinical course of the condition (e.g. developmental delays, comorbidities), and electroencephalographic (EEG) features. However, because the underlying cause of Dravet Syndrome is genetic, genes have an important role to play in our understanding and management of the condition.
Why does Dravet Syndrome occur?
Dravet Syndrome is caused by a change in the genetic code of one of the brain's proteins, which subsequently alters the way in which the brain functions. In around 90% of cases, the genetic change that causes Dravet Syndrome is 'de novo', meaning the condition is not inherited from parents.
More than 85% of people with Dravet Syndrome have a change (or mutation) in a gene known as SCN1A (short for sodium channel alpha 1 subunit). The SCN1A gene contains instructions (genetic code) for the creation of an important type of protein in the brain, known as a sodium ion channel. A change or mutation in the code of the SCN1A gene may lead to the faulty functioning of this sodium ion channel protein.
The movement of sodium ions in and out of nerve cells helps to control electrical messages in the brain, so a faulty ion channel may cause the person with the gene mutation to experience seizures and a variety of other conditions.
Not all mutations to SCN1A cause Dravet Syndrome
Other SCN1A mutations are associated with less severe forms of epilepsy, such as Genetic Epilepsy with Febrile Seizures + (sometimes described as GEFS+).
Around 10-15% of individuals with a clinical diagnosis of Dravet Syndrome have no detected SCN1A mutation. In some cases, individuals might have a mutation in genes other than SCN1A that mimic Dravet Syndrome.
The characteristics of individuals with mutations in these non-SCN1A genes may sometimes appear so similar to Dravet Syndrome that no reliable distinction can be drawn on clinical grounds alone. Find out more about these non-SCN1A genes and their relationship to Dravet Syndrome here.
It is important to know that a negative test for SCN1A does not prevent a clinical diagnosis of Dravet Syndrome, nor does it stop families from accessing support provided by DSUK.
The role of genetic testing
Genetic testing is helpful in many different ways. A confirmative, also called "positive" test for a genetic mutation can confirm a clinical diagnosis of Dravet Syndrome. This helps prevent misdiagnosis, avoids further unnecessary investigations, and enables earlier and better-informed treatment choices, which may lead to better seizure control, ultimately improving quality of life.
A genetic test is especially beneficial for very young children (babies and infants), when it can sometimes be difficult to obtain a clear diagnosis of Dravet Syndrome on clinical grounds alone. However, at any age, having a clear diagnostic label supported by a genetic test, can lead to better-informed treatment choices and improved access to additional therapies and services.
Families have also reported that genetic testing gives "an answer" to possibly years of uncertainty. At the same time, we know from experience that testing can be an emotional and difficult time for families. The outcome may just be the start of their Dravet journey. Whether a test turns out to be positive or negative, genetic counselling is always recommended.
The genetic test for Dravet Syndrome is a simple blood test, available free of charge via the NHS in the UK. The test looks to see if there is a change in the genetic code. It is possible to test for just one gene (for example SCN1A) but it is becoming common to test for a panel of epilepsy-related genes. Find out more about genetic testing and counselling here.
It is important to know that a "negative" test for SCN1A (i.e. no mutation was found) does not prevent a clinical diagnosis of Dravet Syndrome, nor does it stop families from accessing support provided by DSUK.
At DSUK, we are here to support all families living with Dravet Syndrome
Several members of our Dravet community have genetic mutations other than SCN1A. Our Family Relationship Manager, Teresa, has an adult daughter whose genetic test revealed a SCN1B mutation. You can read Teresa's and Amy's story here.
Ultimately, Dravet Syndrome remains a clinical diagnosis and all affected patients, irrespective of genetic status, should have access to appropriate therapies and support services.
Click on the images below to find out more information about SCN1A, genetic changes beyond SCN1A, genetic testing and what our understanding of the genetics of Dravet Syndrome means for future treatments.
Many thanks to our Medical Advisory Board member, Andreas Brunklaus, for his assistance in co-authoring this section of the DSUK website.
SCN1A and Dravet Syndrome
More than 85% of children and adults diagnosed with Dravet Syndrome have a mutation in a gene known as SCN1A. Find out more about SCN1A mutations here.
Genetic Changes Beyond SCN1A
In a small amount of cases, a clinical diagnosis of Dravet Syndrome is linked to a mutation in genes other than SCN1A. Find out more about these here.
The genetic test for Dravet Syndrome is a free, simple blood test. Here we discuss the benefits of testing, what the process involves, and why genetic counselling is always recommended.
Gene Therapies in Dravet Syndrome
Advances in our understanding of genetics mean that the medical and scientific environment is changing quickly for Dravet Syndrome, with promising new treatments on the horizon. Find out more here.