The autism spectrum disorder phenotype in children with tuberous sclerosis complex: A systematic review and meta‐analysis

Abstract

AbstractAimTo investigate the phenotype in autistic children with tuberous sclerosis complex (TSC), specifically autism spectrum disorder (ASD) severity and characteristics, intellectual ability, adaptive and executive function, language skills, attention‐deficit/hyperactivity disorder features, and internalizing and externalizing behaviours.MethodMEDLINE, Embase, and the Cochrane Library were searched up to March 2021. Studies that investigated predefined phenotypic factors in children with TSC‐ASD were included according to the Preferred Reporting Items for Systematic review and Meta‐Analysis Protocols (PRISMA‐P) guidelines. Two authors independently reviewed titles, abstracts, full texts, and extracted the data. Risk of bias and GRADE assessments were completed.ResultsThirty‐four studies with 3160 children with TSC, 30% with ASD, were included. Meta‐analysis found that 90% (95% confidence interval 86%–94%) of children with TSC‐ASD have an intellectual disability. There was some evidence to suggest that young children with TSC‐ASD and idiopathic ASD have a similar pattern of severity and behaviour. Overall, data about phenotypic characteristics were limited.InterpretationA greater proportion of children with TSC‐ASD are reported to have an intellectual disability than children with idiopathic ASD. Early intervention should consider the needs of children with a high likelihood of intellectual disability. Research is needed to better understand the impacts of intellectual disability and other co‐occurring difficulties on adaptive function, participation, and quality of life in TSC‐ASD.What this paper adds Most children with tuberous sclerosis complex (TSC) and autism spectrum disorder (ASD) have an intellectual disability. TSC‐ASD early intervention planning should consider the high likelihood of intellectual disability. Quality of life and the functional impact of intellectual disability in TSC‐ASD are not understood. Little is known about co‐occurring difficulties in TSC‐ASD.