Intellectual functioning and behavior in Dravet syndrome: A systematic review

Dravet syndrome (DS) is a developmental and epileptic encephalopathy with onset in the first year of life. At onset, the child displays normal development, but during the second year of life, stagnation/slowing of neurodevelopment is seen. In addition to difficulties with intellectual development, many children display behavioral problems including autistic features, and difficulties with attention and hyperactivity.

The aim of the present study was to systematically review studies that have focused on the prevalence of cognitive/developmental quotients (DQs) consistent with intellectual disability (ID), deficits in adaptive behavior, autism spectrum disorder (ASD), attention-deficit hyperactivity disorder (ADHD), and behavioral difficulties. A secondary aim was to consider possible factors associated with intellectual and behavioral outcomes in individuals with DS.

A systematic review using PubMed and Scopus following the Preferred Reporting Items for Systematic Review (PRISMA) guidelines was conducted on the 24th of September 2019. Study quality was rated by two researchers using the National Institutes of Health (NIH) Quality assessment tools.

Twenty-nine studies met inclusion criteria. The pooled prevalence of ID was 86% (range across studies: 50%-100%). The pooled prevalence for ASD was 31%. The mean level of adaptive behavior was more than 2 standard deviations (SDs) below average. The prevalence of behavioral difficulties on standardized instruments ranged between 37% and 100%. The only factor consistently associated with lower cognitive scores was age with older children having significantly lower cognitive scores than younger children. For behavioral difficulties, the most consistent association was with low health-related quality of life (HRQoL) with better HRQoL associated with fewer behavioral difficulties. Study quality was almost universally poor or fair - 15/29 studies were rated 'poor', 13/29 studies were 'fair', and 1 was 'good'.

The prevalence of cognitive scores consistent with ID is very high in DS. Many patients also have significant deficits in adaptive behavior highlighting that the majority of patients with DS will meet criteria for ID. The prevalence of ASD would also appear to be higher than the general population but studies show a wide range. Behavioral difficulties are common, but most studies have not used instruments adapted to patients with low intelligence quotient/DQ (IQ/DQ). No study used standardized instruments to assess ADHD. Few studies have used comprehensive statistical methods to evaluate possible factors associated with worse cognitive and behavioral outcome.

It should be routine to screen for cognitive and behavioral difficulties for all patients with DS. There is a need for more robust studies regarding intellectual and behavioral disorders in patients with DS. These should be large population-based or multinational studies that employ standardized instruments.