What is Dravet Syndrome
Dravet syndrome is a rare, severe epileptic encephalopathy that typically begins in the first year of life, characterized by prolonged, often fever-triggered seizures, developmental regression, and multiple neurological impairments, with approximately 80% of cases caused by mutations in the SCN1A gene. 1, 2
Clinical Presentation and Onset
Dravet syndrome presents with distinctive clinical features that evolve over time:
- Initial seizures typically occur between 4-12 months of age, often triggered by fever, infections, or vaccinations, and are frequently misdiagnosed as simple febrile seizures 1, 3, 4
- Seizures are characteristically prolonged and may present as convulsive status epilepticus, with the convulsive seizure being the most common type 2, 4
- Early development appears normal initially, but cognitive and motor regression becomes evident in the second year of life 1, 4
Seizure Characteristics
The seizure patterns in Dravet syndrome are pleomorphic and include:
- Generalized tonic-clonic seizures are the predominant seizure type, often prolonged and requiring rescue medication 5, 6
- Myoclonic seizures, alternating hemiconvulsions, and focal seizures emerge as the syndrome progresses 2, 4
- Seizures remain drug-resistant despite multiple antiepileptic medications, with polypharmacy typically required 6, 2
Genetic Basis
The majority of Dravet syndrome cases result from pathogenic mutations in the SCN1A gene, which encodes the alpha-1 subunit of voltage-gated sodium channels critical for neuronal excitability 1, 3, 2
- Most mutations are de novo (spontaneously occurring rather than inherited) 2, 4
- Genetic testing is now available and recommended when the clinical diagnosis is unclear, allowing for earlier confirmation 2, 4
Associated Neurological and Behavioral Impairments
Beyond seizures, Dravet syndrome causes progressive multisystem dysfunction:
- Cognitive decline and developmental delays are progressive and long-lasting after the first seizure episode 1, 2
- Motor impairments including ataxia, balance disorders, and gait disturbances are common 7, 1
- Behavioral abnormalities develop over time and contribute to overall disability 1, 6
Diagnostic Features
The diagnosis is primarily clinical, supported by genetic testing when available 2, 4:
- EEG is typically normal at disease onset, which can delay diagnosis 4
- Neuroimaging reveals no structural brain lesions 4
- The combination of prolonged febrile seizures in infancy, subsequent developmental regression, and multiple seizure types should prompt consideration of Dravet syndrome 4
Epidemiology and Prognosis
Dravet syndrome is classified among rare genetic neurodevelopmental disorders with prevalence estimates suggesting it is relatively frequent among rare epileptic encephalopathies 8
- The condition is debilitating and challenging to manage, requiring lifelong specialized multidisciplinary care 8, 1
- Risk of sudden unexpected death in epilepsy (SUDEP) is elevated, particularly with uncontrolled generalized tonic-clonic seizures and status epilepticus 6
Treatment Landscape
Three medications have documented efficacy as adjunctive therapies: stiripentol, cannabidiol, and fenfluramine 9, 5, 7, 5, 6
- Stiripentol demonstrated 71% and 67% responder rates (>50% seizure reduction) in two placebo-controlled trials when added to clobazam and valproate 5
- A "start low, go slow" approach is recommended for medication dosing in Dravet syndrome patients 9
- Cannabidiol is FDA-approved as adjunctive therapy for patients with inadequate response to other regimens 9