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

Abstract

To 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. MEDLINE, 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. Thirty-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. A 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. 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.