Dravet syndrome

Overview

Dravet syndrome, also known as severe myoclonic epilepsy of infancy (SMEI), is a rare and lifelong form of epilepsy that begins in the first year of life. It is characterized by prolonged, frequent seizures that are often triggered by fever or illness, as well as developmental delays and a higher risk of sudden unexpected death in epilepsy (SUDEP). Dravet syndrome is classified as a developmental and epileptic encephalopathy, meaning that seizures and abnormal brain activity contribute to cognitive and behavioral impairments over time.

Causes

Most cases of Dravet syndrome are caused by mutations in the SCN1A gene, which encodes a protein essential for proper functioning of sodium channels in the brain. These channels help regulate electrical activity in neurons. When mutated, the channels do not function properly, leading to excessive and uncontrolled brain activity (seizures). Dravet syndrome is typically the result of a de novo mutation—meaning it occurs spontaneously and is not inherited from either parent. However, rare familial cases have also been reported.

Symptoms

Symptoms of Dravet syndrome typically begin in the first year of life, often between 4 to 8 months of age, and progress as the child grows. Common symptoms include:

• Prolonged febrile seizures: Seizures triggered by fever, often lasting longer than 5 minutes.

• Multiple seizure types: Including generalized tonic-clonic, myoclonic (muscle jerks), focal, and atypical absence seizures.

• Photosensitivity: Seizures may be triggered by flashing lights or visual patterns.

• Developmental delays: Including speech delays, motor impairment, and slowed cognitive growth, typically emerging in the second year of life.

• Ataxia: Unsteadiness and difficulty with coordination and balance.

• Behavioral issues: Hyperactivity, irritability, and autistic traits are common.

• Increased risk of SUDEP: Sudden unexpected death in epilepsy, a major concern in this condition.

Diagnosis

Early diagnosis of Dravet syndrome is crucial for proper management. The diagnosis is based on a combination of clinical presentation and genetic testing:

• Medical history: Review of seizure patterns, age of onset, and developmental milestones.

• Electroencephalogram (EEG): May show generalized spike-wave or multifocal discharges, although early EEGs can be normal.

• MRI: Typically normal in the early stages but used to rule out structural causes of seizures.

• Genetic testing: Confirms the diagnosis by identifying mutations in the SCN1A gene or other associated genes.

Treatment

There is no cure for Dravet syndrome, but treatment focuses on managing seizures and improving quality of life. A combination of therapies is often required:

• Anti-seizure medications: Commonly used drugs include clobazam, valproic acid, stiripentol, and topiramate. Newer medications like cannabidiol (CBD) and fenfluramine have shown promise in reducing seizure frequency.

• Avoid sodium channel blockers: Drugs like carbamazepine and lamotrigine can worsen seizures and should be avoided.

• Ketogenic diet: A high-fat, low-carbohydrate diet that may help reduce seizures in some children.

• Physical, speech, and occupational therapy: To address developmental delays and improve daily functioning.

• Rescue medications: Such as rectal diazepam or intranasal midazolam to manage prolonged seizures.

Prognosis

The prognosis for Dravet syndrome varies, but most individuals will have lifelong epilepsy and developmental challenges. While seizure frequency may improve in adolescence, cognitive and motor impairments often persist. With proper treatment and support, many children with Dravet syndrome can achieve developmental progress, but they may require lifelong care. Early intervention, tailored therapies, and seizure control can significantly improve quality of life. However, due to the risk of SUDEP and status epilepticus, ongoing medical monitoring is essential.