Cortical dysplasia and autistic trait severity in children with Tuberous Sclerosis Complex: a clinical epidemiological study

Sabine E Mous,Leontine W Ten Hoopen,Iris E Overwater,Gwendolyn C Dieleman,Marie-Claire Y De Wit,Jorieke Duvekot,Maarten H Lequin,Rita Vidal Gato

doi:10.1007/s00787-017-1066-z

Abstract

Tuberous Sclerosis Complex (TSC) is characterized by a high prevalence of autism spectrum disorders (ASD). Little is known about the relation between cortical dysplasia and ASD severity in TSC. We assessed ASD severity (using the Autism Diagnostic Observation Scale), tuber and radial migration line (RML) count and location, and cognitive functioning in 52 children with TSC and performed regression and mediation analyses. Tuber and RML count were strongly positively related to ASD severity. However, when correcting for cognitive functioning, the majority of associations became insignificant and only total tuber count remained associated to the severity of restricted/repetitive behaviors. Occipital RML count remained associated with overall ASD severity, and social communication/interaction deficit severity specifically. This study shows the important explanatory role of cognitive functioning in the association between cortical dysplasia and ASD severity, and the relevance of separately studying the two ASD subdomains.

Highlights

Tuberous Sclerosis Complex (TSC) is an autosomal dominant disorder affecting 1 in 6000 people, caused by inactivating TSC1 or TSC2 variants
We found only a single study that previously investigated the relation between a quantitative measure of autism spectrum disorders (ASD) severity and tuber count, which did not find an association between cortical tuber count or location and overall ASD severity [19]
We aim to investigate the association between cortical dysplasia and a clinical observational quantitative measure of ASD severity, and to study the role of cognitive functioning in this association

Summary

Introduction

Tuberous Sclerosis Complex (TSC) is an autosomal dominant disorder affecting 1 in 6000 people, caused by inactivating TSC1 (chromosome 9) or TSC2 (chromosome 16) variants. Mutations in the TSC1 or TSC2 gene lead to a upregulation of the mTOR pathway, causing uncontrolled cell growth and abnormal differentiation and the proliferation of benign overgrowths of cells and tissue in several organ systems including the brain, skin, kidneys, heart, eyes, lungs and bones [1]. In the brain this may lead to cortical dysplasia. No new tubers arise, but in older children tubers may calcify or become cystic [1] Another form of cortical dysplasia is the presence of radial migration lines (RMLs).

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