Somatic Overgrowth Predisposes to Seizures in Autism Spectrum Disorders

Giulia Valvo, Sara Baldini, Francesca Brachini, Fabio Apicella, Angela Cosenza, Anna Rita Ferrari, Renzo Guerrini, Filippo Muratori, Maria Francesca Romano, Filippo M. Santorelli, Raffaella Tancredi, Federico Sicca

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background:Comorbidity of Autism Spectrum Disorders with seizures or abnormal EEG (Autism-Epilepsy Phenotype) suggests shared pathomechanisms, and might be a starting point to identify distinct populations within the clinical complexity of the autistic spectrum. In this study, we tried to assess whether distinct subgroups, having distinctive clinical hallmarks, emerge from this comorbid condition.Methods:Two-hundred and six individuals with idiopathic Autism Spectrum Disorders were subgrouped into three experimental classes depending on the presence of seizures and EEG abnormalities. Neurobehavioral, electroclinical and auxological parameters were investigated to identify differences among groups and features which increase the risk of seizures. Our statistical analyses used ANOVA, post-hoc multiple comparisons, and the Chi-squared test to analyze continuous and categorical variables. A correspondence analysis was also used to decompose significant Chi-squared and reduce variables dimensions.Results:The high percentage of children with seizures (28.2% of our whole cohort) and EEG abnormalities (64.1%) confirmed that the prevalence of epilepsy in Autism Spectrum Disorders exceeds that of the general population. Seizures were associated with severe intellectual disability, and not with autism severity. Interestingly, tall stature (without macrocephaly) was significantly associated with EEG abnormalities or later onset seizures. However, isolated macrocephaly was equally distributed among groups or associated with early onset seizures when accompanied by tall stature.Conclusions:Tall stature seems to be a phenotypic "biomarker" of susceptibility to EEG abnormalities or late epilepsy in Autism Spectrum Disorders and, when concurring with macrocephaly, predisposes to early onset seizures. Growth pattern might act as an endophenotypic marker in Autism-Epilepsy comorbidity, delineating distinct pathophysiological subtypes and addressing personalized diagnostic work-up and therapeutic approaches.

Original languageEnglish
Article numbere75015
JournalPLoS One
Volume8
Issue number9
DOIs
Publication statusPublished - Sep 23 2013

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seizures
Electroencephalography
Seizures
epilepsy
Megalencephaly
Epilepsy
Autistic Disorder
Comorbidity
Biomarkers
Analysis of variance (ANOVA)
Autism Spectrum Disorder
autism
Intellectual Disability
Population
biomarkers
Analysis of Variance
analysis of variance
Phenotype
phenotype
therapeutics

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Somatic Overgrowth Predisposes to Seizures in Autism Spectrum Disorders. / Valvo, Giulia; Baldini, Sara; Brachini, Francesca; Apicella, Fabio; Cosenza, Angela; Ferrari, Anna Rita; Guerrini, Renzo; Muratori, Filippo; Romano, Maria Francesca; Santorelli, Filippo M.; Tancredi, Raffaella; Sicca, Federico.

In: PLoS One, Vol. 8, No. 9, e75015, 23.09.2013.

Research output: Contribution to journalArticle

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abstract = "Background:Comorbidity of Autism Spectrum Disorders with seizures or abnormal EEG (Autism-Epilepsy Phenotype) suggests shared pathomechanisms, and might be a starting point to identify distinct populations within the clinical complexity of the autistic spectrum. In this study, we tried to assess whether distinct subgroups, having distinctive clinical hallmarks, emerge from this comorbid condition.Methods:Two-hundred and six individuals with idiopathic Autism Spectrum Disorders were subgrouped into three experimental classes depending on the presence of seizures and EEG abnormalities. Neurobehavioral, electroclinical and auxological parameters were investigated to identify differences among groups and features which increase the risk of seizures. Our statistical analyses used ANOVA, post-hoc multiple comparisons, and the Chi-squared test to analyze continuous and categorical variables. A correspondence analysis was also used to decompose significant Chi-squared and reduce variables dimensions.Results:The high percentage of children with seizures (28.2{\%} of our whole cohort) and EEG abnormalities (64.1{\%}) confirmed that the prevalence of epilepsy in Autism Spectrum Disorders exceeds that of the general population. Seizures were associated with severe intellectual disability, and not with autism severity. Interestingly, tall stature (without macrocephaly) was significantly associated with EEG abnormalities or later onset seizures. However, isolated macrocephaly was equally distributed among groups or associated with early onset seizures when accompanied by tall stature.Conclusions:Tall stature seems to be a phenotypic {"}biomarker{"} of susceptibility to EEG abnormalities or late epilepsy in Autism Spectrum Disorders and, when concurring with macrocephaly, predisposes to early onset seizures. Growth pattern might act as an endophenotypic marker in Autism-Epilepsy comorbidity, delineating distinct pathophysiological subtypes and addressing personalized diagnostic work-up and therapeutic approaches.",
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AU - Cosenza, Angela

AU - Ferrari, Anna Rita

AU - Guerrini, Renzo

AU - Muratori, Filippo

AU - Romano, Maria Francesca

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AU - Tancredi, Raffaella

AU - Sicca, Federico

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