Dravet Syndrome
Dravet Syndrome is a severe, genetic, developmental, and epileptic encephalopathy. The ILAE classifies it as a genetic epilepsy syndrome and highlights its key features: a normal start in life followed by the onset of drug-resistant seizures and progressive developmental decline.
Presentation and Clinical Features
Age of Onset: Typically begins in the first year of life, often around 6 months.
Seizure Profile: The seizure course is progressive and complex.
Initial Phase: The first seizures are often prolonged febrile seizures or febrile status epilepticus, which can be unilateral. These are often triggered by fever, infections, or hot baths.
Later Progression: As the child gets older, a variety of seizure types emerge, including myoclonic seizures, atypical absence seizures, and focal seizures, often occurring in clusters. The seizures are highly drug-resistant.
Developmental Trajectory: A key feature is the progressive developmental deterioration. The child initially has normal development, but as seizures become more frequent and diverse, they develop cognitive and language impairments. Other common issues include ataxic gait, sleep disturbances, and behavioural problems.
Genetics: The majority of cases (around 80%) are caused by a mutation in the SCN1A gene, which encodes a voltage-gated sodium channel. Other genetic mutations have also been identified. Genetic testing is crucial for an early and accurate diagnosis, especially in infants with recurrent, prolonged, or atypical seizures.
Investigations
Diagnosis: Diagnosis is made based on the clinical features and confirmed with genetic testing.
EEG: The EEG is often normal early on but later shows non-specific abnormalities like diffuse background slowing, generalised polyspikes, or multifocal epileptiform discharges.
Genetic Testing: Targeted genetic testing for the SCN1A gene is the gold standard. The ILAE recommends considering testing in any child with recurrent febrile seizures that are prolonged or unusual.
Management and Prognosis
Treatment: The seizures are notoriously difficult to control, and a multifaceted approach is often necessary.
First-Line Medications: Valproate, Clobazam, and Topiramate are often used first. Stiripentol, a specific add-on drug, is also highly effective. Cannabidiol (CBD) has also been approved and shows good efficacy.
Medications to AVOID: Sodium channel blockers, such as Lamotrigine, Carbamazepine, and Phenytoin, should be avoided as they can worsen seizures.
Rescue Medication: Rectal or buccal benzodiazepines (e.g., midazolam) are crucial for managing prolonged seizures or status epilepticus.
Prognosis and Complications: The prognosis is generally poor, with significant long-term cognitive and motor impairment. There is also a substantial increased risk of SUDEP (Sudden Unexpected Death in Epilepsy).
Distinction from GEFS+: It’s important to distinguish Dravet Syndrome from Genetic Epilepsy with Febrile Seizures Plus (GEFS+). GEFS+ has a better prognosis with fewer seizures and a normal developmental outcome. Unlike Dravet Syndrome, GEFS+ usually remits by puberty.