The epilepsy phenotype in adult patients with intellectual disability and pathogenic copy number variants

Abstract

Purpose: To characterize the electroclinical features of epilepsy associated with intellectual disability and pathogenic copy number variations (CNVs) METHODS: we prospectively investigated 61 adult patients with epilepsy and intellectual disability or other neurodevelopmental disorders. We performed high resolution SNP-Array analysis in order to detect clinical relevant chromosomal microdeletions and microduplications. An ordinal logistic regression model was fitted with 34 demographic, clinical and EEG-related variables in order to identify the epilepsy phenotype of patients with pathogenic CNVs.

Results: chromosome microarray analysis identify non-polymorphic CNVs in 33 patients analyzed: 11 had an established pathogenic microdeletion/microduplication, 22 were carriers of CNVs of unknown clinical significance. Univariate analysis revealed a significant association between pathogenic CNVs and 3 electroclinical variables considered, specifically atypical absence seizures (p<0.05), tonic seizures (p<0.05), epileptic spasms (p<0.01).

Conclusions: high resolution SNP-Array analysis should be evaluated in adult patients with intellectual disability and epilepsy with peculiar electroclinical features, specifically atypical absence seizures, tonic seizures, and epileptic spasms, resembling a Lennox-Gastaut syndrome without a clear structural lesion.

Keywords: Copy number variations; Epilepsy; Intellectual disability; Lennox-Gastaut syndrome; SNP-array.