Dravet Syndrome (DS)

Dravet syndrome (DS) is a rare form of severe childhood epileptic encephalopathy. The disease is characterized by frequent, intractable seizures that are often triggered by an initial febrile seizure of long duration (status epilepticus). Repeated seizures result in developmental delay or regression, cognitive impairment, and motor deficits.¹

Clinical Diagnostic Criteria for DS

According to the Dravet Syndrome Foundation, a clinical diagnosis of DS requires at least 4 of the following diagnostic criteria²:

• Normal or near-normal cognitive status and motor development before the onset of seizures
• Occurrence of 2 or more seizures with or without fever before the age of 12 months
• Occurrence of 2 or more seizures lasting longer than 10 minutes
• History of multiple types of seizures, including myoclonic, generalized tonic-clonic, and hemiclonic seizures
• History of seizures continuing after the age of 2 years after failure to respond to first-line antiseizure medications

Clinicians should be alert to seizures associated with fevers, hot baths or high temperatures, and vaccinations. Other clinical features of DS include developmental delay or regression after the first year of life, speech delay, behavioral problems, and cognitive impairment.²

Read more about DS clinical features

Diagnostic Genetic Testing for DS

More than 85% of individuals with DS have SCN1A gene mutations. These may be inherited in an autosomal-dominant pattern or, in most cases, arise de novo (spontaneously). Nearly 90% of the SCN1A mutations in patients with DS are de novo mutations. SCN1A mutations are not exclusive to DS, and mutations in other genes also contribute to the development of DS.³ These genes include GABRG2, SCN1B, SCN2A, and PCDH19.⁴

If clinicians suspect DS, they may recommend genetic testing, especially for known SCN1A abnormalities.

Read more about DS genetics

The consensus of an international panel of experts regarding the diagnosis and management of DS is that genetic testing should be strongly encouraged in developmentally normal children between 2 and 15 months of age who have had a single prolonged hemiclonic seizure lasting between 5 and 29 minutes or focal or generalized status epilepticus lasting 30 minutes or longer following vaccination or during a fever.⁵

The same panel of experts moderately recommend genetic testing for children with the following clinical presentations⁵:

• Children aged 2 to 5 months with a history of a single prolonged generalized tonic-clonic seizure following vaccination or during a fever
• Children aged 6 to 15 months with a history of a single prolonged generalized convulsive seizure lasting 5 to 29 minutes following vaccination
• Children aged 2 to 15 months with a history of a single episode of afebrile, convulsive status epilepticus or a single prolonged afebrile hemiclonic seizure

Read more about DS guidelines

Diagnostic Imaging Studies for DS

Electroencephalography

In many children with DS, the findings on electroencephalography (EEG) often are normal at the time of the initial presentation. However, as the child ages, the EEG findings evolve, demonstrating abnormalities at approximately 4 to 6 months, such as generalized spike waves, focal or multifocal spike waves, spike-wave discharges, and generalized diffuse or focal slowing. EEG abnormalities appear during the first year of life in approximately 43% of patients with DS. Demonstrating the progression, EEG abnormalities are evident in 90% of patients with DS between the ages of 1 and 2 years.⁶

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Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) can reveal structural abnormalities of the brain in a small minority of patients with DS, such as cortical dysplasia, focal atrophy in the cerebrum or cerebellum, arachnoid cysts, ventricular enlargement, and hippocampal sclerosis.⁷

Positron Emission Tomography/Single-Photon Emission Computed Tomography

Very few positron emission tomography (PET) and single-photon emission computed tomography (SPECT) studies have been conducted in individuals with DS. These imaging studies reveal predominantly unilateral, but in some cases bilateral, areas of hypoperfusion. Patients with lateralized seizures demonstrate cortical hypometabolism on PET. However, neuroimaging studies cannot determine whether the areas of cortical hypometabolism are the cause or the consequence of repeated seizures.⁷ 

Read more about DS etiology

References 

1. Genetic epilepsy with febrile seizures plus. MedlinePlus. Accessed March 11, 2023.
2. What is Dravet syndrome? Dravet Syndrome Foundation. Accessed March 11, 2023.
3. SCN1A and Dravet syndrome. Dravet Syndrome UK. Accessed March 11, 2023.
4. Connelly MB. Dravet syndrome: diagnosis and long-term course Can J Neurol Sci. 2016:43:S3-S8. doi:10.1017/cjn.2016.243. 
5. Bender AC, Morse RP, Scott RC, Holmes GL, Lenck-Santini PP. SCN1A mutations in Dravet syndrome: impact of interneuron dysfunction on neural networks and cognitive outcome. Epilepsy Behav. 2012;23(3):177-186. doi:10.1016/j.yebeh.2011.11.022
6. Minato E, Myers KA. Age-related evolution of EEG in Dravet syndrome: meta-analysis of 155 patients. Seizure. 2021;91:108-111. doi:10.1016/j.seizure.2021.06.007
7. Guerrini R, Striano P, Catarino C, Sisodiya SM. Neuroimaging and neuropathology of Dravet syndrome. Epilepsia. 2011;52 Suppl 2:30-34. doi:10.1111/j.1528-1167.2011.02998.x

Reviewed by Hasan Avcu, MD, on 3/13/2023.

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Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT

Maria Arini Lopez, PT, DPT, CSCS, CMTPT, CIMT is a freelance medical writer and Doctor of Physical Therapy from Maryland. She has expertise in the therapeutic areas of orthopedics, neurology, chronic pain, gastrointestinal dysfunctions, and rare diseases especially Ehlers Danlos Syndrome.