How Dravet syndrome became a model for studying childhood genetic epilepsies

In this issue of Brain , Brunklaus et al. report a study of 241 patients with Dravet syndrome carrying a SCN1A mutation, with the aim of identifying predictors of developmental outcome and determining specific clinical and demographic characteristics. The electroclinical features of a large cohort were collected and analysed prior to genetic testing. A total of 355 patients were diagnosed with Dravet syndrome, but the authors selected only the 241 (68%) who were positive for a mutation of SCN1A . Patients who were excluded had not been tested for mutations in other genes that could potentially cause overlapping phenotypes, such as protocadherin 19 (Depienne et al ., 2009).Dravet syndrome was first described briefly in French as severe myoclonic epilepsy in infancy (Dravet, 1978). In 1981, the same series was presented at the XIIIth Epilepsy International Congress and published 1 year later. Over the last 20 years, numerous series of patients have been reported, confirming the initial description, but also underlining variability of the clinical picture. The classic syndrome is defined by onset in an otherwise healthy infant during the first year of life, presenting febrile or afebrile and generalized or unilateral clonic or tonic clonic seizures, often long lasting, later associated with myoclonic, atypical absence and focal seizures. These are all resistant to drug treatment, and accompanied by slowing of developmental skills, as well as motor and behavioural disturbances. The EEG shows generalized and multifocal abnormalities whereas neuroimaging is normal. It quickly became apparent that a number of patients do not present with the complete semiology, mainly because the myoclonic component may be missing, and typical and atypical or ‘borderline’ forms are recognized, also showing an unfavourable prognosis. With time, the syndrome …