Dravet Syndrome (DS)

Dravet syndrome (DS), formerly known as severe myoclonic epilepsy of infancy (SMEI), describes a rare, chronic form of childhood epilepsy that is refractory to treatment. It is a type of developmental epileptic encephalopathy in which intractable seizures result in severe developmental delay and cognitive impairment.¹ 

Seizures due to DS often manifest within the first 2 to 15 months of life.¹ It is estimated that between 3% and 8% of children who experience seizures within the first year of life may have DS.² Seizures in DS often occur along with a fever and are prolonged, lasting 15 to 30 minutes or longer. This febrile convulsive status epilepticus occurs frequently in children with DS, requiring urgent medical attention.³ 

Around 85% of patients with DS demonstrate a mutation or deletion in the SCN1A gene, which encodes a voltage-gated sodium channel protein.⁴

Incidence and Prevalence of Dravet Syndrome

The incidence of DS is estimated at around 1 in every 15,700 live births, with over 80% of these neonates exhibiting SCN1A gene abnormalities.¹ The prevalence of DS is estimated to range from 1 in 20,000 to 1 in 40,000 individuals.² 

In the United States, a study published in 2015 reported the incidence of DS in a cohort of infants born at Kaiser Permanente Northern California between 2007 and 2010. The researchers suggested that the incidence of DS is twice as common as formerly believed, occurring in around 1 in 15,700 births.⁵

Mortality occurs in up to 20% of children and adolescents with DS before reaching adulthood due to sudden unexpected death in epilepsy (SUDEP), prolonged seizures, serious infections, or seizure-related accidents.⁶

Read more about DS prognosis

Age Factors of MF

Dravet syndrome affects infants, usually with an onset between 2 and 15 months of age.¹ Approximately 15% to 20% of individuals with DS die before reaching adulthood; however, many do reach adulthood, with individuals known to be living with DS into their 60s.⁷

Read more about DS life expectancy

Sex Factors of MF

Dravet syndrome affects male children twice as often as female children.^8,9

Biological sex may also influence treatment efficacy. According to murine model studies investigating a potential gene therapy for DS, mortality, treatment efficacy, and behavioral characteristics differed between male and female mice. Following injection of the gene therapy into the cerebrospinal fluid, female mice with a mutated SCN1A gene demonstrated more pronounced survival rates than male mice; however, untreated female mice demonstrated higher mortality rates.¹⁰

In the same study, prior to treatment, male mice with DS demonstrated increased motor hyperactivity, fear, and anxiety as well as decreased learning and memory capacity compared to female mice. Following gene therapy administration, male mice exhibited reductions in seizures and improved motor activity and performance scores. It is unclear whether these sexually divergent features in mice will translate to humans following similar treatment.¹⁰

Read more about DS treatment

Another recent murine study reported that female mice experienced higher numbers of seizures and demonstrated an increased risk of SUDEP compared to male mice.¹¹

Read more about DS complications

Geographical and Race/Ethnicity Factors of DS

Dravet syndrome does not appear to affect specific geographic regions or ethnic groups more frequently than others. Approximately 35,000 individuals living in the United States, Canada, Germany, France, the United Kingdom, and Japan have DS.⁶

References

1. What is Dravet syndrome? Dravet Syndrome Foundation. Accessed March 13, 2023.
2. Joshi C, Wirrell E. Dravet syndrome. Epilepsy Foundation. August 24, 2020. Accessed March 13, 2023.
3. Dravet syndrome. Epilepsy Action. Accessed March 13, 2023.
4. Dravet syndrome. Orphanet. Updated April 2021. Accessed March 13, 2023.
5. Wu YW, Sullivan J, McDaniel SS, et al. Incidence of Dravet syndrome in a US population. Pediatrics. 2015;136(5):e1310-e1315. doi:10.1542/peds.2015-1807
6. Dravet syndrome fact sheet. Stoke Therapeutics. Accessed March 13, 2023. 
7. Catarino CB, Liu JYW, Liagkouras I, et al. Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology. Brain. 2011;134(10):2982-3010. doi:10.1093/brain/awr129
8. Incorpora G. Dravet syndrome. Ital J Pediatr. 2009;35:27. doi:10.1186/1824-7288-35-27
9. 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
10. Niibori Y, Lee SJ, Minassian BA, Hampson DR. Sexually divergent mortality and partial phenotypic rescue after gene therapy in a mouse model of Dravet syndrome. Hum Gene Ther. 2020;31(5-6):339-351. doi:10.1089/hum.2019.225
11. Gerbatin RR, Augusto J, Boutouil H, Reschke CR, Henshall DC. Sexual dimorphism in epilepsy and comorbidities in Dravet syndrome mice carrying a targeted deletion of exon 1 of the Scn1a gene. bioRxiv. Published online August 28, 2021. doi:10.1101/2021.08.27.457904

Reviewed by Harshi Dhingra, MD, on 3/12/2023.

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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.