Dravet syndrome (previously known as “severe myoclonic epilepsy in infancy”) is a severe epilepsy defined in the 1989 international classification
by “febrile and afebrile generalized and unilateral, clonic or tonic clonic seizures, that occur in the first year of life in an otherwise normal infant, and are later associated with myoclonus, atypical absences and partial seizures. All seizure types are resistant to antiepileptic drugs. Developmental delay becomes apparent within the second year of life and is followed by definite cognitive impairment and personality disorders.” In 2001,
Dravet syndrome was included among the epileptic encephalopathies. Its genetic aetiology was first demonstrated the same year by the discovery of a mutation on the SCN1A gene in seven patients,
and then confirmed in 70-80 % of patients in many other studies. According to the new terminology proposed in the 2010 revision,
Dravet syndrome is now recognized as a genetic epilepsy. It is not one of the most frequent severe epilepsies affecting infants in the first year of life. In one recent epidemiological study, in Sweden, its estimated incidence was 1 in 33,000 live births, and its prevalence as of December 31, 2011, was reported to be 1 in 45,700 children aged less than 18 years.
Nonetheless, it is now well known by many child neurologists, and for several reasons. First, it has become a model of genetic epilepsy, and animal models allow experimental studies focused on the underlying mechanisms of the disease.
Second, the clinical characteristics of the typical form are defined well enough to allow for an early diagnosis.
Third, although the epileptic seizures are highly pharmacoresistant, a specific therapeutic strategy exists, due to the new drug stiripentol, which allows one to avoid the most severe seizures in many patients.
Dravet syndrome is not merely epilepsy, as it is an encephalopathy that also causes motor and cognitive impairment and is likely to create a more or less severe handicap that becomes apparent as over time.
There are numerous uncertainties concerning the causes of this complex symptomatology. What are the respective roles of genetic background (including the SCN1A mutations and other possible genes and gene modifiers) and the epilepsy itself (including seizure types, seizure frequency, occurrence of status epilepticus and environmental contributors)? All these factors should be taken into account for prognosis and treatment. Because it is rare, non-specialists are not yet aware of Dravet syndrome, and there are few possibilities for parents to easily meet other families confronted with the disease. So, when possible, it is important to give the most accurate information on the syndrome to medical professionals and to those involved in the care of patients. That is the aim of this symposium, which proposes topics of particular interest for families. Families always have questions about diagnosis, medical treatment and long-term outcomes. This topic will be covered by Drs. Mary Connolly and Elaine Wirrell. Families also want to provide their children with the best quality of life in spite of the disease, which is also the objective of the doctors who treat them. Dr. Peter Camfield will discuss how doctors can help families in this regard.
Charlotte Dravet has the following disclosure: Biocodex, consultant, honoraria.
Commission on Classification and Terminology of the International League Against Epilepsy: proposal for revised classification of epilepsies and epileptic syndromes. Epilepsia. 1989;30(4):389-399.
Engel, J. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia. 2001;42(6):796-803.
Claes, L, Del Favero, J, Ceulemans, B, Lagae, L, Van Broeckhoven, C, De Jonghe, P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet. 2001;68(6):1327-1332.
Berg, AT, Berkovic, SF, Brodie, MJ, Buchhalter, J, Cross, JH, van Emde Boas, W, et al. Revised terminology and concepts of the organization of seizures and epilepsies: report of the ILAE commission on classification and terminology, 2005-2009. Epilepsia. 2010;51(4):676-685.
Rosander, C, Hallböök, T. Dravet syndrome in Sweden: a population-based study. Dev Med Child Neurol. 2015 March 13. doi: 10.1111/dmcn.12709. [Epub ahead of print].
Kalume, F, Yu, FH, Westenbroek, RE, Scheuer, T, Catterall, WA. Reduced sodium current in Purkinje neurons from Nav1.1 mutant mice: implications for ataxia in severe myoclonic epilepsy in infancy. J Neurosci. 2007;27(41):11065-11074.
Dravet, C. The core Dravet syndrome. Epilepsia. 2011;52(Suppl 2):3-9.
Chiron, C. Stiripentol for the treatment of Dravet syndrome. Orphan Drugs: Res Rev. 2014;4:29-38.