ABSTRACT
AIM: 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. METHOD: 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. RESULTS: 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. INTERPRETATION: 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. 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.
Subject(s)
Autism Spectrum Disorder , Intellectual Disability , Tuberous Sclerosis , Humans , Intellectual Disability/etiology , Phenotype , Quality of Life , Tuberous Sclerosis/complications , Tuberous Sclerosis/geneticsABSTRACT
AIM: To investigate associations between clinical factors and the development of autism spectrum disorder (ASD) in children with tuberous sclerosis complex (TSC), specifically seizures, electroencephalogram abnormalities, tubers and other neurostructural abnormalities, and genetic factors. METHOD: MEDLINE, Embase, PubMed, the Cochrane Library, and Web of Science were searched until January 2019. Studies that considered the predefined factors for development of ASD in children with TSC were included, following PRISMA-P guidelines. Two authors independently reviewed titles, abstracts, and full texts, extracted data, and assessed risk of bias. RESULTS: Forty-two studies with 3542 children with TSC were included. ASD was associated with a history of seizures (odds ratio [OR] 3.79, 95% confidence interval [CI] 1.77-8.14), infantile spasms compared with other seizure types (OR 3.04, 95% CI 2.17-4.27), onset of any seizure type during infancy (OR 2.65, 95% CI 1.08-6.54), and male sex (OR 1.62, 95% CI 1.23-2.14). There was no association with tuber number, tuber location, or genotype. INTERPRETATION: While a causal link between seizures and ASD in children with TSC cannot be inferred, a strong association between seizures and ASD in children with TSC, particularly with seizure onset during infancy and specifically infantile spasms, is present. Children with TSC and infant-onset seizures should be monitored for emerging features of ASD. What this paper adds Seizures and autism spectrum disorder (ASD) strongly associate in children with tuberous sclerosis complex (TSC). Infant-onset seizures and infantile spasms are particularly strongly associated with ASD in TSC.
