Dravet Syndrome (DS)

Dravet syndrome (DS) is a rare form of childhood epileptic encephalopathy characterized by frequent, prolonged, intractable seizures that contribute to developmental delays, cognitive and speech impairment, behavioral issues, problems with growth and nutrition, and dysautonomia.¹ 

The onset of seizures in DS typically occurs within the first year of life. Approximately 3% to 8% of children who experience seizures before 12 months of age may have DS.²

Life Expectancy in DS

Dravet syndrome is a chronic, lifelong condition requiring ongoing care and support from a multidisciplinary team. The seizures experienced in DS are very difficult to manage with antiseizure medications and may affect life expectancy. Management requires a combination of various therapies to reduce seizure frequency and intensity.²

Up to 85% of children with DS reach adulthood, while 15% to 20% die in childhood or adolescence.^2,3 Most deaths occur prior to 10 years of age (73%), with a mean age at death of 8.7±9.8 years. Approximately 93% of deaths in individuals with DS occur before the age of 20 years.⁴

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Common Causes of Death in DS

Around half of deaths (49%) in patients with DS are related to sudden unexpected death in epilepsy (SUDEP), a fatal complication of the disease. Other causes of death experienced by individuals with DS include status epilepticus (32%), accidents or drowning during seizure episodes (8%), infections (5%), respiratory insufficiency and generalized hypoxemia due to acute respiratory distress syndrome, global ischemic brain injury, ketoacidosis, and postoperative multiple organ failure, as well as unknown causes.⁴

Read more about DS risk factors

Age Progression and Adulthood in DS

Individuals with DS can live to middle or late adulthood, with patients known to be living at 60 years of age.⁵

According to the literature, epileptic seizures in adults with DS are less frequent and severe than those experienced in childhood. The incidence of convulsive status epilepticus also decreases significantly with age, potentially contributing to the decreased mortality risk in adulthood.⁶

Although adults with DS remain sensitive to fevers and temperature variations, these factors have a milder impact on seizure intensity and frequency than during infancy.⁶

Most adults with DS have significant motor, cognitive, and behavioral impairments, and most become totally or partially dependent on others, with very few able to live independently with adequate external support.⁶

Read more about DS complications

Factors Affecting Life Expectancy in DS

Life Expectancy Relative to Treatment

Effective and immediate medical intervention during seizure episodes may decrease the risk of death during prolonged seizures. Development of more efficacious drugs to improve control over the typically refractory seizures in DS may reduce the frequency, duration, and/or severity of seizures. This may improve long-term cognitive and behavioral outcomes as well as reduce the likelihood of status epilepticus or SUDEP.⁶

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Life Expectancy Relative to Genetics

Another factor that may play a significant role in determining seizure severity in patients with DS is genetics.⁶ More than 80% of individuals with DS demonstrate abnormalities in the SCN1A gene.¹

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Developing precision medications that target the predominant SCN1A gene abnormalities found in most patients with DS and creating more rapid and accurate diagnostics to identify and diagnose the condition earlier may also improve long-term outcomes, optimize treatments, and reduce mortality rates among children with DS.⁷

Read more about DS experimental therapies

Preventive Measures Against Mortality in DS

Advancements in technology and improving treatments to better manage acute seizure situations, particularly those involving status epilepticus, may decrease the risk of mortality in patients with DS. Patients should be instructed to avoid the use of soft pillows and determine ways to prevent respiratory depression, which can contribute to SUDEP, especially while sleeping.⁶ SUDEP usually occurs during sleep.¹

Central apnea resulting in bradycardia, which may lead to SUDEP, requires treatment to rapidly restore ventilation. In these cases, cardiac pacemakers are not appropriate interventions.⁸ In contrast, patients with DS who have severe ictal heart rate changes that may eventually lead to SUDEP via ictal asystole may require the preventive implantation of a pacemaker.⁹ 

References

1. Dravet syndrome. National Organization for Rare Disorders (NORD). Updated July 24, 2020. Accessed March 13, 2023.
2. Dravet syndrome. Cleveland Clinic. Accessed March 13, 2023.
3. Treatments and outcomes. Dravet Syndrome UK. Accessed March 13, 2023.
4. Shmuely S, Sisodiya SM, Gunning WB, Sander JW, Thijs RD. Mortality in Dravet syndrome: a review. Epilepsy Behav. 2016;64:69-74. doi:10.1016/j.yebeh.2016.09.007
5. 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
6. Genton P, Velizarova R, Dravet C. Dravet syndrome: the long-term outcome. Epilepsia. 2011;52(s2):44-49. doi:10.1111/j.1528-1167.2011.03001.x
7. Li W, Schneider AL, Scheffer IE. Defining Dravet syndrome: an essential pre‐requisite for precision medicine trials. Epilepsia. 2021;62(9):2205-2217. doi:10.1111/epi.17015
8. Kim Y, Bravo E, Thirnbeck CK, et al. Severe peri-ictal respiratory dysfunction is common in Dravet syndrome. J Clin Invest. 2018;128(3):1141-1153. doi:10.1172/JCI94999
9. Mazzola L, Rheims S. Ictal and interictal cardiac manifestations in epilepsy. A review of their relation with an altered central control of autonomic functions and with the risk of SUDEP. Front Neurol. 2021;12:642645. doi:10.3389/fneur.2021.642645

Reviewed by Harshi Dhingra, MD, on 3/25/2023.

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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.