Veronica Hood, PhDResearch Coordinator

www.dravetfoundation.org

What is Dravet syndrome?

• Severe, often intractable form of epilepsy• Seizure onset 1-18 months, often febrile • Various seizure types• Generally normal cognitive/motor development before seizure onset• Variable behavioral and developmental delays emerge with age• Movement, balance, and orthopedic comorbidities• Associations with autonomic, metabolic, and immune dysfunction• 15-20% mortality rate due to SUDEP, SE, seizure-related accidents, and infections

What causes Dravet syndrome?• SCN1A mutation (80%)• Encodes the Nav1.1 sodium channel• Haploinsufficiency• Primarily expressed by inhibitory interneurons• SCN1A spectrum of disorders

Genetic Testing for Dravet Syndrome

• Testing is often delayed• Many of the diagnostic criteria are not apparent in the first year of life • Infants with Dravet syndrome initially experience typical development

• Diagnosis informs treatment

Genetic testing via an epilepsy panel should be considered in patients exhibiting any of the following:

• 2 or more prolonged seizures by 1 year of age• 1 prolonged seizure and any hemiclonic seizure by 1 year of age• 2 seizures of any length that seem to affect alternating sides of the body• History of seizures prior to 18 months of age and later emergence of myoclonic and/or absence

seizures

How prevalent is Dravet syndrome?• Incidence estimated at 1:15,700

• ~17,850 patients in the US

• 1,321 patients registered in US Family Network • ~18% are adult patients

• Still missing many patients.• Adult patients?• Misdiagnosis

• Non-coding mutations

Wu, E., et. al. (2015). Incidence of Dravet Syndrome in a US Population. Pediatrics 136(5): 1310-e1315. doi: 10.1542/peds.2015-1807.Carville G, et. al. (2018) Aberrant inclusion of a poison exon causes Dravet syndrome and related SCN1A-associated genetic epilepsies. Amer J of Human Gen 103:1022-1029. doi: 10.1016/j.ajhg.2018.10.023

DSF Mission Statement

“The mission of Dravet Syndrome Foundation (DSF) is to

aggressively raise funds for Dravet syndrome and related

epilepsies; to support and fund research; increase awareness;

and to provide support to affected individuals and families”

DSF Programs• Professional Programs

• Research Grants (4 mechanisms, $75-150K)• Research Roundtable• Biennial conference

• Advocacy and Support Programs• Parent Support Groups• DSF Family Network• Day of Dravet Workshops• Patient Assistance Grants• Initiatives to provide additional support to families

• Fundraising

Progress in Dravet-Related Research• Dravet syndrome described in 1978

• First associations with SCN1A in early 2000s• Research still lagged

• DSF founded in 2009• Began funding pilot grants in 2010• Over $4.6M directed to research since• NIH funding has also increased greatly

DSF FoundedSCN1A assoc

w/ Dravet

Progress in Dravet-Related Research• 4 Grant mechanisms

• Basic Research ($150K/2yr)• Post-doctoral Fellowships ($50K/ 1yr)• Clinical Research ($150K/2yr)• Clinician Researcher ($75K/1yr)• Special RFAs

• Recent Progress in Research• Multiple mouse models• Zebrafish à clinical trials• Incidence nearly twice as common as previous estimate• Treatment Consensus• Disease modifying treatments

DSF Provides Education• Social Media• Information Rich Website• Decoding Dravet Blog• Research Review• Monthly Newsletter• Biennial Conference• Day of Dravet• Educational Webinar Series• Professional Partnerships

What’s still missing?

• A cure • Attention to other comorbidities• An understanding of SUDEP• Support for adult patients and families• Increased testing

• Invitae “Behind the Seizure”

Thank you!

www.dravetfoundation.org

veronica@dravetfoundation.org