Copy number variants in absence epilepsy: Further complications of the picture

After years of largely unsuccessful association studies attempting to detect genetic variants underlying common epilepsies, the recent identification of copy number variants (CNVs) in epilepsy has generated a lot of excitement. CNVs are defined as genomic deletions or duplications larger than 1 kb and up to several Mb in size. A proportion occur at genomic hotspots (recurrent CNVs), whereas others can occur anywhere in the genome. Although individually rare, these CNVs collectively constitute the single largest risk factor for sporadic epilepsies known to date. Depending on the exact phenotype, CNVs have been reported in up to 28% of patients with epilepsy.(1) Subsequently, exon-disrupting deletions in a range of genes previously implicated in a variety of neurodevelopmental disorders were also identified in patients with epilepsy.(2-4) Genetic generalized epilepsy (GGE), either associated or not associated with intellectual disability, is the most commonly reported phenotype in patients carrying these CNVs. The GGEs comprise a large group of phenotypically heterogeneous disorders with a known or presumed genetic cause, which may vary from rare monogenic cases to complex polygenic inheritance.