Mortality in Dravet syndrome: search for risk factors in Japanese patients.

A questionnaire survey was conducted in Japan to investigate the causes and prevalence of death related to Dravet syndrome. The questionnaire was delivered to 246 hospitals at which physicians were treating childhood epilepsy to gain information about the total number of patients with Dravet syndrome and the prevalence of early death due to the disorder. Responses to the survey were collected from 91 hospitals, and a total of 63 of 623 patients with Dravet syndrome had died. Data from 59 of these patients were analyzed. The age at death for these patients ranged from 13 months to 24 years and 11 months, with a median age of 6 years and 8 months. The causes of mortality included sudden death in 31 patients (53%), acute encephalopathy with status epilepticus (SE) in 21 patients (36%), drowning in 6 patients (10%), and other causes in one patient (1%). The incidence of sudden death reached a first peak at 1-3 years of age and a second peak at 18 years and older. In contrast, the incidence of acute encephalopathy with SE reached a peak at 6 years of age. Seven of the 10 patients who underwent SCN1A mutation analysis exhibited positive mutations but exhibited no consistent phenotype. The prevalence of Dravet syndrome-related mortality was 10.1%. The incidence of sudden death and acute encephalopathy with SE was higher in infancy (1-3 years) and at early school ages (with a peak at 6 years), respectively. Neither the treatment nor the number of seizures was associated with any cause of mortality. Factors leading to a fatal outcome are difficult to predict.