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, 103 (Pt A), 106844

Language Predictors of Autism Spectrum Disorder in Young Children With Tuberous Sclerosis Complex


Language Predictors of Autism Spectrum Disorder in Young Children With Tuberous Sclerosis Complex

Alexandra Schoenberger et al. Epilepsy Behav.


Background: Epilepsy has previously been implicated in the development of autism spectrum disorder (ASD) in the setting of tuberous sclerosis complex (TSC). However, the role of language in this relationship is unclear, and the specific relationship between ASD, epilepsy, and language development in this population has not been well-studied.

Objectives: The objectives the study were to identify the role of early language in subsequent development of ASD, evaluate the impact of epilepsy as a covariate on language development, and evaluate the relationship between epilepsy, language development, and development of ASD.

Methods: This study included 154 children ages 3-36 months with TSC who were enrolled in the TSC Autism Center of Excellence Research Network (TACERN), a multicenter, prospective observational study to identify biomarkers of ASD. Developmental and autism-specific assessments were administered longitudinally. Appropriate variables from the Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behavior Scales, 2nd Edition (VABS-II), and Preschool Language Scales, 5th Edition (PLS-5) were used to assess patients' language skills. At 36 months, clinical best estimate, which was based on clinical assessment and observation, was used to determine a diagnosis of ASD.

Results: By 12 months, all language variables on the MSEL, PLS-5, and VABS-II significantly predicted an ASD diagnosis at 36 months. Age at seizure onset was associated with language scores in that later seizure onset was associated with improved language scores on the MSEL, VABS-II, and PLS-5. Seizure onset prior to 6 months was associated with a diagnosis of ASD at 36 months. Higher seizure frequency negatively correlated with language scores at 12 months and beyond. Higher seizure frequency was also associated with an ASD diagnosis at 36 months. When looking at the relationship between epilepsy, language, and ASD diagnosis, by 18 months, language scores were more associated with a later ASD diagnosis at 36 months compared with age at seizure onset, which was a better predictor of later ASD diagnosis earlier in development.

Conclusion: Analysis of language variables and epilepsy characteristics from 6 to 36 months and ASD diagnosis at 36 months revealed significant relationships between all three variables. While the direction of these relationships needs further research, epilepsy, language, and the development of ASD are integrally related in young children with TSC.

Keywords: Autism spectrum disorder; Development; Language; Seizures; Tuberous sclerosis complex.

Conflict of interest statement

Declaration of competing interest JKC has received consulting fees and travel expenses from Roche. MS reports grant support from Novartis, Roche, Pfizer, Ipsen, LAM Therapeutics, and Quadrant Biosciences unrelated to this project. He has served on Scientific Advisory Boards for Sage, Roche, Celgene and Takeda. DAK has received consulting and speaking fees and travel expenses from Novartis and additional research support from the National Institute of Neurological Disorders and Stroke of the NIH (U01-NS082320, U54-NS092090, P20-NS080199), the Tuberous Sclerosis Alliance, the Van Andel Research Institute, Novartis, and Upsher-Smith Pharmaceuticals. In addition, he serves on the professional advisory board and international relations committee for the Tuberous Sclerosis Alliance and the editorial board of Pediatric Neurology. DAP has received research support from NIH (U01-NS082320; U54-NS092090; U01-NS092595); research support, consulting fees, and travel reimbursement from Curemark, LLC; and research support from Biomarin and Novartis. Joyce Wu receives grant support and serves on the Scientific Advisory Boards/Speakers' Bureaus for Novartis and Greenwich Biosciences/GW Pharmaceutical unrelated to this project. The remaining authors have no conflicts of interest.

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