Dravet Syndrome Factsheet

Clinical features
Dravet syndrome, also called severe myoclonic epilepsy of infancy (SMEI), appears during the first year of life with frequent febrile seizures. After the age of 5 years, febrile seizures decrease while other types of seizures typically arise, including myoclonus (involuntary muscle spasms) and status epilepticus. Children with Dravet syndrome typically experience poor language and motor development, hyperactivity, and social difficulty. The degree of impairment correlates with frequency of seizures. Seizures tend to lessen in severity after puberty; however, they rarely resolve completely. Approximately 16% of individuals with Dravet syndrome have complete resolution of their seizures. For most, anticonvulsant treatment is lifelong. Due to intractable seizures, this syndrome usually causes progressive dementia. Most teenagers are dependent on caregivers.

Genetics
30-80% of cases of Dravet are associated with mutations in the SCN1A gene, located on chromosome 2. The gene normally functions in neuronal sodium channels. The molecular abnormality caused by SCN1A mutations causes hyperexcitability of the cortical network. Mutations in the SCN1A gene can also cause various other phenotypes, including isolated febrile seizures, generalized epilepsy with febrile seizures plus (GEFS+), and intractable childhood epilepsy with generalized tonic-clonic seizures (ICE-GTC). The phenotype of SCN1A-related seizure disorders can vary even within the same family.

Inheritance
SCN1A variants can be inherited, or sporadic/de novo. The likelihood of an inherited variant depends upon the phenotype. The majority (95%) of individuals with a Dravet phenotype have a de novo mutation. On the other hand, the majority (95%) of individuals with a GEFS+ phenotype have an inherited variant. When familial, SCN1A mutations are inherited in an autosomal dominant pattern. Each child of an individual with an SCN1A mutation has a 50% chance of inheriting the mutation. However, the phenotype of SCN1A-related seizure disorder can vary widely even within the same family, with some family members showing no symptoms.

Clinical testing
Sequence analysis of the SCN1A gene detects between 73-92% of mutations, and deletion/duplication analysis detects between 827% of mutations.

Management
Seizures are difficult to control in Dravet syndrome, but may be reduced by some anticonvulsant drugs and a ketogenic diet.

References
GeneReviews: SCN1A-Related Seizure Disorders at http://www.ncbi.nlm.nih.gov/books/NBK1318/ NINDS Dravet Syndrome Info Page at www.ninds.nih.gov/disorders/dravet_syndrome/dravet_syndrome.htm

Published September 2013 NCHPEG All rights reserved