Deep developmental phenotyping in children with tuberous sclerosis complex, with and without autism

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.