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

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.