Rutgers Biomedical and Health Sciences

What is Dravet Syndrome?

A clinical diagnosis for an intractable (incurable) epilepsy that initially appears in infancy resulting in impaired cognitive and motor function. Discovered in 1978 by Charlotte Dravet.

Classified in1989 by the International League Against Epilepsy (ILAE) and is now described as a genetic and developmental epilepsy syndrome with onset in infancy.
Also known as Severe Myocolinc Epilepsy of Infancy (SMEI) Occurrence is rare with only 500 cases reported to date worldwide. Estimated rate of occurrence is 1/40000 children.

What causes Dravet Syndrome?

Prior to molecular genetics, it was unclear whether it was inherited or acquired (such as a reaction to vaccination). In 2001, research identified that 70% of Dravet patients have a loss-of function mutation on the SCN1A gene for the -subunit of voltage-gated sodium channel . 25% of females without the SCN1A gene mutation have a mutation of PCDH19 gene which encodes for calciumdependent CAM in the brain. In 2011, research suggested a link to GABRA1 gene mutations which code for the inhibitory GABA receptor. Considered to be the result of de novo mutation, a mutation that is not inherited, but present in the egg or sperm.

Manifestation
Infant will have normal development until the onset

of the first seizure typically in the first year of life. Early seizures are often fever-induced and are tonic clonic seizures and unilateral seizures. After the first year, they will develop different types of seizures and they will be longer lasting. Absence, focal, and myoclonic seizures occur.

IMPACT
Despite frequent seizures in the first few years, development mentally continues normally. By the third year, there is a noticeable deterioration of mental progression. Children may not form sentences properly and may have erratic behavior. ADHD is common. Beyond age 10, most patients are institutionalized. 15% mortality rate by age 20.

Treatment of Dravet Syndrome

To prevent febrile (fever-induced) seizures, hot conditions should be avoided. Treatment is very limited as Dravet syndrome is very pharmacoresistant. Antiepileptic drugs may be ineffective/adverse effects. Different drugs and combinations tried until effective. Can sometimes be treated with anticonvulsants including: clobazam, clonazepam, stiripentol, valproic acid. Prolonged seizures can be stopped with benzodiazepine. Experimental nature of drugs means they are not covered by insurance. A ketogenic diet may help.

References
Al-Baradie, Raidah S. Dravet syndrome, what is new? Neuroscience Center, King Fahd Specialist

Hospital, Kingdom of Saudi Arabia Neurosciences (Riyadh) 18:11-7. 2013 Arzimanoglou, A. (2009), Dravet syndrome: From electroclinical characteristics to molecular biology. Epilepsia, 50: 39. doi: 10.1111/j.1528-1167.2009.02228.x Causative Gene May Differ Among Patients with Dravet Syndrome. American Epilepsy Society. December 3, 2011. http://www.aesnet.org/go/press-room/press-release-archive/newsreleases?mode=view&id=128 Chiron, C. and Dulac, O. (2011), The pharmacologic treatment of Dravet syndrome. Epilepsia, 52: 7275. doi: 10.1111/j.1528-1167.2011.03007.x De Jonghe, P. (2011), Molecular genetics of Dravet syndrome. Developmental Medicine & Child Neurology, 53: 710. doi: 10.1111/j.1469-8749.2011.03965.x Miller IO, Sotero de Menezes MA. SCN1A-Related Seizure Disorders. 2007 Nov 29 [Updated 2011 Nov 10]. In: Pagon RA, Bird TD, Dolan CR, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-. http://www.ncbi.nlm.nih.gov/books/NBK1318/ Claudia B. Catarino, Joan Y.W. Liu. Dravet syndrome as epileptic encephalopathy: evidence from long-term course and neuropathology. Brain.134 (10): 2982-3010 doi:10.1093/brain/awr129