Borlot F, et al. – Physicians designed this cross-sectional study to assess the prevalence of pathogenic copy number variations (CNVs) and identify possible candidate CNVs and genes in patients with epilepsy and intellectual disability. In this study, the high prevalence of pathogenic CNVs underscored the importance of microarray analysis in adults with unexplained childhood–onset epilepsy and intellectual disability. To assess the effects of deletions and duplications that overlap specific genes, further studies and comparison with similar cases were required.

• The physicians used the genome-wide microarray to assess a cohort of 143 adults with unexplained childhood-onset epilepsy and intellectual disability who were recruited from the Toronto Western Hospital epilepsy outpatient clinic from January 1, 2012, through December 31, 2014.
• For this study, the inclusion criteria were following :
  • Pediatric seizure onset with ongoing seizure activity in adulthood
  • Intellectual disability of any degree
  • No structural brain abnormalities or metabolic conditions that could explain the seizures.
• They performed DNA screening using genome-wide microarray platforms.
• They evaluated pathogenicity of CNVs based on the American College of Medical Genetics guidelines.
• They used the Residual Variation Intolerance Score to assess genes within the identified CNVs that could play a role in each patient’s phenotype.

• The physicians investigated 143 probands among 2335 patients (mean [SD] age, 24.6 [10.8] years; 69 male and 74 female).
• In this study, 23 probands (16.1%) and 4 affected relatives (2.8%) (mean [SD] age, 24.1 [6.1] years; 11 male and 16 female) presented with pathogenic or likely pathogenic CNVs (0.08-18.9 Mb).
• 5 of the 23 probands with positive outcomes (21.7%) had more than 1 CNV reported.
• With CNVs inherited from a parent in 4 probands (17.4%), parental testing showed de novo CNVs in 11 (47.8%).
• 16 of 23 probands (69.6%) presented with previously cataloged human genetic disorders and/or defined CNV hot spots in epilepsy.
• They identified 8 nonrecurrent rare CNVs that overlapped 1 or more genes correlated with intellectual disability, autism, and/or epilepsy: 2p16.1-p15 duplication, 6p25.3-p25.1 duplication, 8p23.3p23.1 deletion, 9p24.3-p23 deletion, 10q11.22-q11.23 duplication, 12p13.33-13.2 duplication, 13q34 deletion, and 16p13.2 duplication.
• Five genes were of particular interest due to their potential pathogenicity in the corresponding phenotypes and least tolerability to variation: ABAT, KIAA2022, COL4A1, CACNA1C, and SMARCA2.
• ABAT duplication was correlated with Lennox-Gastaut syndrome and KIAA2022 deletion with Jeavons syndrome.