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Journal of Pediatric Neurology 2017; 15(03): 123-128
DOI: 10.1055/s-0037-1601445
Review Article
Georg Thieme Verlag KG Stuttgart · New York

New Perspectives in Autism Spectrum Disorder associated with Tuberous Sclerosis

Arianna Benvenuto
1   Child Neurology and Psychiatry Unit, Department of System Medicine, University of Rome Tor Vergata, Roma, Italy
,
Martina Siracusano
1   Child Neurology and Psychiatry Unit, Department of System Medicine, University of Rome Tor Vergata, Roma, Italy
,
Federica Graziola
1   Child Neurology and Psychiatry Unit, Department of System Medicine, University of Rome Tor Vergata, Roma, Italy
,
Romina Moavero
1   Child Neurology and Psychiatry Unit, Department of System Medicine, University of Rome Tor Vergata, Roma, Italy
2   Department of Neuroscience and Neurorehabilitation, Bambino, Gesù Children's Hospital, IRCCS, Rome, Italy
,
Luigi Mazzone
1   Child Neurology and Psychiatry Unit, Department of System Medicine, University of Rome Tor Vergata, Roma, Italy
2   Department of Neuroscience and Neurorehabilitation, Bambino, Gesù Children's Hospital, IRCCS, Rome, Italy
,
Leonardo Emberti Gialloreti
3   Department of Biomedicine and Prevention, University of Rome, University of Rome Tor Vergata, Rome, Italy
4   Centre for Communication and Neurorehabilitation Research-CNAPP, Rome, Italy
,
Paolo Curatolo
1   Child Neurology and Psychiatry Unit, Department of System Medicine, University of Rome Tor Vergata, Roma, Italy
› Author Affiliations
Further Information

Publication History

20 December 2016

12 February 2017

Publication Date:
04 April 2017 (online)

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Abstract

Recent advances in molecular genetics and preclinical studies of tuberous sclerosis complex (TSC) have helped to better understand the pathophysiology of TSC-related autism spectrum disorder (ASD). Furthermore, developmental studies have shown that infants with TSC begin to diverge from the neurotypical trajectories at the age of 6 months. Early abnormalities are often characterized by a delay in nonverbal cognitive skills, such as fine motor and visual reception domains followed by qualitative impairment of social communication. The expanding possibilities of an early diagnosis of TSC should increasingly allow the prompt identification of a population of infants at high risk for developing ASD. A presymptomatic diagnosis of TSC could facilitate not only the prospective investigation of developmental trajectories and early markers of ASD but also the evaluation of the efficacy of early interventions. Early identification of infants at high-risk for ASD, such as TSC infants, can allow designing individualized treatment strategies to address deficits in specific developmental domains associated with autism. The involvement of mammalian target of rapamycin (mTOR) in determining the behavioral phenotypes associated with TSC led to the hypothesis that mTOR inhibitors could also have a benefit on ASD symptoms. After the promising results from preclinical studies administrating rapamycin, clinical trials studying mTOR inhibitors are now undergoing.

Keywords

tuberous sclerosis complex - epilepsy - autism spectrum disorder - early intervention - mTOR inhibitors - parent-mediated intervention - predictors - risk factors