Genotype Phenotype Interactions of Epilepsy in Children and Adolescents with Autism Spectrum Disorders

Background:  Five to 30% of children with ASD develop epilepsy by twenty years of age. Children with autism and epilepsy have an increased risk of morbidity and mortality. Despite the enormous strides in understanding the molecular pathogenesis of ASD, little is known of the common molecular mechanisms between autism and epilepsy. Genotype phenotype studies of epilepsy and autism would add to the knowledge base regarding the overlap of genomic mechanisms and clinical phenotypes common to these two childhood neurological disorders.

Objectives: This report describes proposed clinical and genotype parameters to aid in identification and evaluation of distinct subgroups of children (250) with Autism Spectrum Disorders (ASD) and epilepsy. 

Methods:  Systematic comparisons across 12 subgroups divided by genotype and age of first words were performed to identify clinical differences across the spectrum of children with ASD alone versus those with ASD and epilepsy.

Results:  Brain growth (head circumference) in ASD and epilepsy may differ significantly from children and adolescents of similar age with ASD alone. Clustering of genomic microarray data by age of first words revealed differences among subgroups in sensory issues, reciprocal social communication, and repetitive behaviors. Putative protein protein interactions networks revealed unique networks involving BMP signaling pathway, acetylcholine synthesis/neurosecretion, and microtubule interactions with the cytoskeleton in ASD/Epilepsy group

Conclusions:  

The current data supports the hypothesis that the molecular pathogenesis of ASD and epilepsy is distinct among ASD populations.