Diagnosis and long-term course of Dravet syndrome

Abstract

Dravet syndrome is a severe infantile-onset epilepsy syndrome with a distinctive but complex electroclinical presentation. A healthy, developmentally normal infant presents at around 6 months of age with convulsive status epilepticus, which may be hemiclonic or generalized; seizures may be triggered by fever, illness or vaccination. The infant typically has further episodes of status epilepticus every month or two, often triggered by fever. Other seizure types including focal dyscognitive seizures, absence and myoclonic seizures develop between 1 and 4 years. Atonic drop attacks and episodes of non-convulsive status may occur. Early development is normal but slows in the second year. Developmental regression may occur, particularly with status epilepticus. EEG studies are initially normal, but after 2 years they show generalized spike-wave and polyspike-wave activity with multifocal discharges. Photosensitivity may be seen. Imaging is normal or shows non-specific findings such as atrophy. Dravet syndrome is associated with mutations of the gene encoding the alpha-1 subunit of the sodium channel, SCN1A, in >70% of patients. These include sequencing mutations and copy number variant anomalies; 90% of mutations arise de novo. PCDH19 mutational analysis is a second-tier test for girls with a Dravet-like picture who do not have SCN1A mutations. Outcome is poor, with intellectual disability in most patients and ongoing seizures. Intellectual impairment varies from severe in 50% patients, to moderate and mild intellectual disability each accounting for 25% cases. Rare patients have normal intellect. The long-term course involves ongoing, brief nocturnal convulsions and a characteristic deterioration in gait.