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Factors associated with autism spectrum disorder in children with tuberous sclerosis complex: a systematic review and

Rebecca A Mitchell1,2,3, Sarah M Barton3,4, A Simon Harvey3,4

  • 1Department of Neurodevelopment and Disability, The Royal Children's Hospital, Parkville, VIC, Australia.

Developmental Medicine and Child Neurology
|January 12, 2021
PubMed

Insights

Seizures, especially infantile spasms and those starting in infancy, are strongly linked to autism spectrum disorder (ASD) in children with tuberous sclerosis complex (TSC). Male sex also showed an association with ASD development in this population.

Area of Science:

  • Neurology
  • Genetics
  • Developmental Pediatrics

Background:

  • Tuberous sclerosis complex (TSC) is a genetic disorder with a high prevalence of neurological complications.
  • Autism spectrum disorder (ASD) is a common neurodevelopmental comorbidity in children with TSC, affecting up to 50% of individuals.
  • Understanding factors associated with ASD development in TSC is crucial for early identification and intervention.

Purpose of the Study:

  • To investigate the association between clinical factors and the development of autism spectrum disorder (ASD) in children with tuberous sclerosis complex (TSC).
  • Specifically examining seizures, electroencephalogram (EEG) abnormalities, tubers, other neurostructural abnormalities, and genetic factors.
  • To provide evidence-based insights for monitoring and managing ASD risk in children with TSC.

Main Methods:

  • A systematic review and meta-analysis adhering to PRISMA-P guidelines.
  • Searched major databases (MEDLINE, Embase, PubMed, Cochrane, Web of Science) up to January 2019.
  • Included 42 studies involving 3542 children with TSC, with independent data extraction and risk of bias assessment.

Main Results:

  • ASD was significantly associated with a history of seizures (OR 3.79) and infantile spasms (OR 3.04).
  • Seizure onset during infancy (OR 2.65) and male sex (OR 1.62) were also associated with increased ASD risk.
  • No significant association was found between ASD and tuber number, tuber location, or specific genotypes.

Conclusions:

  • A strong association exists between seizures, particularly infantile spasms and infant-onset seizures, and ASD in children with TSC.
  • While causality cannot be established, these findings highlight critical risk factors for ASD in this population.
  • Children with TSC experiencing infant-onset seizures warrant close monitoring for emerging ASD features.
Abstract

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