Related Experiment Video
Updated: May 23, 2025
Rapid Detection of Neurodevelopmental Phenotypes in Human Neural Precursor Cells NPCs
Published on: March 2, 2018
Deep developmental phenotyping in children with tuberous sclerosis complex, with and without autism
Rebecca A Mitchell1,2,3, Francesca Lami1,2,3, Sarah M Barton1,2,3
1The Royal Children's Hospital, Parkville, VIC, Australia.
Insights
Autism and tuberous sclerosis-associated neuropsychiatric disorders (TAND) are complex in children with TSC. Language and ADHD assessments are vital for all children with TSC, irrespective of autism or intellectual status.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Genetics
Background:
- Tuberous sclerosis complex (TSC) is a genetic disorder associated with a high prevalence of neuropsychiatric conditions, known as TAND.
- Autism Spectrum Disorder (ASD) is a common co-occurring condition in children with TSC, but its specific characteristics and relationship with other TAND require further elucidation.
- Deep developmental phenotyping offers a comprehensive approach to understanding the complexities of TAND in TSC.
Purpose of the Study:
- To characterize autism and associated TAND in children with TSC using detailed developmental assessments.
- To identify specific co-occurring conditions and developmental profiles in children with TSC, with and without autism.
- To address evidence gaps in the understanding of TAND heterogeneity within a single TSC cohort.
Main Methods:
- A cohort study involving 50 children with TSC.
- Multidisciplinary direct assessments of autism characteristics, intelligence, adaptive function, language, and co-occurring conditions.
- Comparison of developmental and neuropsychiatric profiles between children with and without autism.
Main Results:
- 56% of children with TSC met criteria for autism, exhibiting significant social affect and restricted/repetitive behavior deficits.
- Children with TSC and autism were more likely to be male and have intellectual disability, language impairment, executive dysfunction, and externalizing behaviors.
- Inattentive ADHD symptoms were prevalent in both autistic and non-autistic children with TSC, independent of intellectual ability. Language impairment was also noted in children without autism or intellectual disability.
Conclusions:
- TAND in children with TSC are complex and heterogeneous, with or without autism.
- Formal assessment of language function and ADHD symptoms is recommended for all children with TSC.
- Language function warrants greater consideration in the assessment and classification of TAND.
Aim:
To characterize autism and co-occurring tuberous sclerosis-associated neuropsychiatric disorders (TAND) in children with tuberous sclerosis complex (TSC), addressing evidence gaps by using deep developmental phenotyping in a single cohort.
Method:
This cohort study assessed autism characteristics, intelligence, adaptive function, language, and co-occurring conditions, using multidisciplinary direct assessment, in 50 children with TSC, comparing those with and without autism.
Results:
Autistic children (28, 56%) had moderate mean scores for autistic characteristics (Autism Diagnostic Observation Schedule calibrated severity scores; social affect, 6.9 [standard deviation 2.5]; restricted and repetitive behaviour, 7.1 [standard deviation 2.3], but with considerable variation). Autistic children were more likely to be male (54% vs 18%) and have intellectual disability (79% vs 32%), language impairment (89% vs 50%), executive dysfunction (70% vs 29%), and externalizing behaviours (46% vs 14%). Inattentive attention-deficit/hyperactivity disorder (ADHD) symptoms were frequent in autistic and not-autistic children (74% vs 78%), and not influenced by intellectual ability. Language impairment occurred in 27% without autism or intellectual disability.
Interpretation:
TAND are complex and heterogenous in children with and without autism. Formal assessment of language function and ADHD symptoms should be considered in all children with TSC, regardless of autism categorization or intellectual ability. Language function needs greater consideration within TAND levels and clusters.
Related Concept Videos
01:19Autism Spectrum Disorder
These core symptoms manifest differently among individuals, ranging from mild to severe. The disorder's complexity extends beyond its clinical presentation, encompassing a diverse range of biological, cognitive, and sociocultural influences.
01:35Pedigree Analysis