Dravet syndrome is extremely rare, with an estimated prevalence of 1 in 20,000 ro 40,000 live births across all geographic regions and ethnic groups. It can affect both males and females, though there is a slight male predominance in some studies. The disorder is most often diagnosed in infancy (6-18 months) when seizures first appear, following a period of normal early development.

About 70-80% of Dravet syndrome cases are caused by mutations in the SCN1A gene, which encodes the voltage-gated sodium channel NaV1.1. These mutations disrupt normal neuronal function, leading to hyperexcitability and seizures. In most cases, the mutation comes from a new non-inherited spontaneous mutation of the SCN1A gene, although autosomal dominant inheritance (see RareShare Guide on Genetic Inheritance) is possible in some cases.

Other genetic mutations, though rare, have also been linked to Dravet syndrome, including mutations in the SCN1B, SCN2A and GABRG2 genes. The SCN genes encode for protein components of voltage-gated sodium channels, and GABRG2 encodes for a component of the gamma-aminobutyric acid (GABA) receptor. GABA is the major inhibitory neurotransmitter in the brain, where it acts at GABA-A receptors, which are ligand-gated chloride channels. 

Environmental factors like fever or infection can exacerbate seizures, but are not considered primary causes of the disorder.

Symptoms of Dravet syndrome usually begin in infancy, around 6-12 months of age, following normal development in the first few months of life. 

Seizure Types:  Seizures are the hallmark of Dravet syndrome, and they tend to become more frequent and severe as the child grows. Key seizure types may include:

• Myoclonic seizures (sudden jerks or spasms)

• Tonic-clonic seizures (generalized body stiffening and jerking)

• Focal seizures (affecting one area of the body)

• Absence seizures (brief lapses in awareness)

• Status epilepticus (seizures lasting longer than 5 minutes, which can be life-threatening)

Neurological and Developmental Issues:  

• Developmental delay: Significant delays in motor, language and social development often become apparent by age 2 or 3.

• Cognitive decline: Many children experience regression in cognitive abilities as they age.

• Motor difficulties: These may include uncoordinated movements and ataxia (lack of muscle coordination).

• Speech delays: Speech and language development can be delayed or absent.

• Autistic-like behaviors: Some children may show traits resembling autism, including social withdrawal, repetitive behaviors, and communication difficulties.

• Sleep disturbances: Children with Dravet syndrome often experience irregular sleep patterns and insomnia.

• Sensitivity to temperature: Seizures are often triggered or exacerbated by fever or heat.

• Behavioral Issues:  Hyperactivity and autistic-like behaviors.

Diagnosis of Dravet syndrome is primarily based on clinical observations and genetic testing. Key diagnostic steps include:

1. Clinical Criteria:

   • Seizures typically begin between 6-12 months of age.

   • Multiple seizure types (e.g., myoclonic, generalized tonic-clonic).

   • Seizures triggered by fever or infections.

   • Developmental delay after normal early development.

2. Genetic Testing:

   • SCN1A gene mutation testing is the gold standard for confirming Dravet syndrome. About 70-80% of affected individuals have mutations in this gene.

   • Other genetic testing may include chromosomal analysis or screening for  SCN2A, SCN1B and GABRG2 mutations.

3. EEG (Electroencephalogram) and Neuroimaging:

   • EEG typically reveals generalized or distinct multifocal epileptiform wave discharge patterns.

   • MRI may show mild structural brain abnormalities, but it is generally normal in most cases.

In Dravet syndrome, (1) the seizure type is frequently clonic or hemi-clonic rather than generalized tonic-clonic; (2) the seizures are more prolonged and frequent, even when treated; and (3) hyperthermia is a triggering factor, even when temperature is moderate. The diagnosis is confirmed when other seizure types emerge. EEG, CT, MRI and metabolic studies are usually normal initially. EEG pattern, age of onset and initial seizure semiology distinguish SMEI from Lennox-Gastaut syndrome. While a diagnosis of Dravet syndrome is made clinically, a majority of cases will test positive for an SCN1A gene mutation, helping to confirm diagnosis.

While there is no cure for Dravet syndrome, treatment focuses on seizure control and improving quality of life.

1. Antiepileptic Drugs (AEDs):

   • Valproate and clobazam are commonly used, but they may not control all seizures.

   • Stiripentol and topiramate are effective for many patients.

   • Cannabidiol (CBD oil) has gained recognition for its potential to reduce seizure frequency and has been approved for use in many countries.

2. Other Therapies:

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

   • Vagus nerve stimulation (VNS): This therapy can reduce seizure frequency in some individuals by sending electrical impulses to the brain via the vagus nerve.

   • Surgical options: In rare cases, surgery may be considered for removing seizure foci if seizures are localized and refractory to treatment.

3. Seizure Management:

   • Rescue medications such as diazepam or lorazepam may be needed during prolonged seizures or status epilepticus.

   • Fever management: Preventing and managing fever is critical in preventing seizure exacerbations.

4. Supportive Care:

   • Physical, occupational, and speech therapy are important for managing developmental delays.

   • Behavioral therapy and interventions can help address autism-like behaviors and improve quality of life.

   • Temperature management, trigger avoidance and prepared emergency protocols can be helpful.

It is important to note that some anticonvulsant medications (e.g., carbamazepine, oxcarbazepine, phenytoin, and lamotrigine) may worsen seizures in Dravet syndrome and should be avoided.

1. Avoid medications which may aggravate seizures in patients with Dravet syndrome. These include: lamotrigine (Lamictal); phenytoin (Dilantin, Epanutin); fosphenytoin (Cerebyx, Prodilantin); carbamazepine (Tegretol, Biston, Calepsin, Carbatrol, Epitol, Equetro, Finlepsin, Sirtal, Stazepine, Telesmin, Timonil); oxcarbazepine (Trileptal); vigabatrin (Sabril). *Please note, these drugs may be useful acutely in managing status episodes but are not generally helpful in chronic management. 2. Avoid epilepsy surgery as there is no identifiable focal abnormality. 3. Employ treatments shown to be useful for chronic seizure management in Dravet syndrome based on scientific literature. These include: topirimate (Topamax); valproic acid and derivatives (Depakote, Depakene, Convulex, MicopakineLP); stiripentol (Diacomit); clonazepam (Klonopin); clobazam (Frisium, Urbanyl, Mystan); leviteracetam (Keppra); bromides; ketogenic diet. 4. Consider treatments which may be helpful in Dravet syndrome, but which require further study. These include: vitamin B6 therapy; IVIG therapy; ethosuximide (Zarontin); zonisamide (Zonegran, Excegran) vagus nerve stimulation (VNS). 5. Implement an aggressive acute seizure management protocol, including a fast onset benzodiazepine (Diastat, nasal versed, buccal lorazepam) or paraldehyde for any convulsive seizure lasting longer than 5 minutes, and instructions for when to call 911/emergency dispatch, as well as when to transport to a medical facility. Written hospital seizure protocols should also be determined and are beneficial for patients to have with them at all times. 6. Manage the syndrome on a day-to-day basis by avoiding seizure triggers. Common triggers in Dravet syndrome include, but are not limited to, hyperthermia (from any cause), illness, stress, flickering lights, patterns, and temperature changes. Fevers should always be treated aggressively.

The prognosis for individuals with Dravet Syndrome is typically poor, particularly in terms of seizure control and cognitive development.

• Severe, intractable seizures often persist throughout life.

• Developmental delay and cognitive decline are common and progressive.

• Many individuals experience motor difficulties and a significant proportion will need lifelong care.

• Risk of SUDEP (Sudden Unexpected Death in Epilepsy) is heightened in individuals with Dravet syndrome, especially those with poorly controlled seizures.

• However, with appropriate management, individuals can live into adulthood, although quality of life can be severely impacted by ongoing seizures and developmental impairments.

Dravet Syndrome is a severe, lifelong disorder that presents significant challenges for affected individuals and their families. Early diagnosis and a tailored approach to seizure management, developmental support, and genetic counseling are key in improving the quality of life for patients. However, the disorder remains a major cause of morbidity and mortality among individuals with epilepsy.

As children grow older, partial and myoclonic seizures may lessen, and in some cases disappear, but convulsive seizures typicaly persist. Communication, motor and cognitive functions stabilize, but significant delays remain to varying degrees. Despite being at an increased risk for accident, infection and sudden unexpected death in epilepsy (SUDEP), an individual with Dravet syndrome has an 85% chance of surviving into adulthood. Because this disorder is rare and has relatively recently been identified as a distinct syndrome, little is know about long term prognosis and life expectancy. A patient's outcome can be improved with early implementation of global therapies, including physical, occupational, speech and social/play therapies and an enriched environment. It is also important to employ treatment regimens with proven efficacy; develop and implement seizure management protocols; avoid seizure triggers; and manage the syndrome acutely.

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5. Dravet Syndrome. (n.d.). NORD (National Organization for Rare Disorders). Dravet syndrome.