An Updated Review of Tuberous Sclerosis Complex-Associated Autism Spectrum Disorder

Abstract

Tuberous sclerosis complex (TSC) is a neurocutaneous disorder caused by mutations of either the TSC1 or TSC2 gene. Various neuropsychiatric features, including autism, are prevalent in TSC. Recently, significant progress has been possible with the prospective calculation of the prevalence of autism in TSC, identification of early clinical and neurophysiological biomarkers to predict autism, and investigation of different therapies to prevent autism in this high-risk population. The author provides a narrative review of recent findings related to biomarkers for diagnosis of autism in TSC, as well as recent studies related to the management of TSC-associated autism. Further sophisticated modeling and analysis are required to understand the role of different models—tuber models, seizures and related neurophysiological factors models, genotype models, and brain connectivity models—to unravel the neurobiological basis of autism in TSC. Early neuropsychologic assessments may be beneficial in this high-risk group. Targeted intervention to improve visual skill, cognition, and fine motor skills with later addition of social skill training can be helpful. Multicenter, prospective studies are ongoing to identify if presymptomatic treatment with vigabatrin in patients with TSC can improve outcomes, including autism. Several studies indicated reasonable safety of everolimus in young children, and its potential application in high-risk infants with TSC, before the closure of the temporal window of permanent changes, maybe undertaken shortly.