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Title: Defining Dravet syndrome: An essential pre-requisite for precision medicine trials.
Austin Authors: Li, Wenhui;Schneider, Amy L ;Scheffer, Ingrid E 
Affiliation: Murdoch Children's Research Institute and Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Parkville, Vic., Australia
Epilepsy Research Centre
The Florey Institute of Neuroscience and Mental Health
Children's Hospital of Fudan University, Shanghai, China
Medicine (University of Melbourne)
Issue Date: 2021
Date: 2021
Publication information: Epilepsia 2021; 62(9): 2205-2217
Abstract: The classical description of Dravet syndrome, the prototypic developmental and epileptic encephalopathy, is of a normal 6-month-old infant presenting with a prolonged, febrile, hemiclonic seizure and showing developmental slowing after age 1 year. SCN1A pathogenic variants are found in >80% of patients. Many patients have atypical features resulting in diagnostic delay and inappropriate therapy. We aimed to provide an evidence-based definition of SCN1A-Dravet syndrome in readiness for precision medicine trials. Epilepsy patients were recruited to the University of Melbourne Epilepsy Genetics Research Program between 1995 and 2020 by neurologists from around the world. Patients with SCN1A pathogenic variants were reviewed and only those with Dravet syndrome were included. Clinical data, including seizure and developmental course, were analyzed in all patients with SCN1A-Dravet syndrome. Two hundred and five patients were studied at a median age of 8.5 years (range 10 months to 60 years); 25 were deceased. The median seizure-onset age was 5.7 months (range 1.5-20.6 months). Initial seizures were tonic-clonic (52%) and hemiclonic (35%), with only 55% being associated with fever. Only 34% of patients presented with status epilepticus (seizure lasting ≥30 minutes). Median time between first and second seizure was 30 days (range 4 hours to 8 months), and seven patients (5%) had at least 6 months between initial seizures. Median ages at onset of second and third seizure types were 9.1 months (range 3 months-25.4 years) and 15.5 months (range 4 months-8.2 years), respectively. Developmental slowing occurred prior to 12 months in 27%. An evidence-based definition of SCN1A-Dravet syndrome is essential for early diagnosis. We refine the spectrum of Dravet syndrome, based on patterns of seizure onset, type, and progression. Understanding of the full spectrum of SCN1A-Dravet syndrome presentation is essential for early diagnosis and optimization of treatment, especially as precision medicine trials become available.
DOI: 10.1111/epi.17015
ORCID: 0000-0001-5260-7187
Journal: Epilepsia
PubMed URL: 34338318
Type: Journal Article
Subjects: SCN1A
Dravet syndrome
developmental and epileptic encephalopathy
phenotypic spectrum
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