An international group of investigators at University of Washington, Seattle, USA, and various centers in Australia, New Zealand, Canada, and Israel evaluated 315 patients with epileptic encephalopathies for rare copy number variants (CNVs) using a whole-genome oligonucleotide array. Twenty five (7.9%) patients carried rare CNVs thought to contribute to their phenotype, one half being pathogenic. Several novel candidate genes for epilepsy were uncovered. Array comparative genomic hybridization (CGH) should be considered in the genetic evaluation of patients with epileptic encephalopathy characterized by severe epilepsy and cognitive regression. [1]
COMMENT. Epileptic encephalopathies (EEs) are severe epilepsies in which the epilepsy activity contributes to cognitive impairment or regression and poor outcome. Most EEs begin in infancy or childhood, often associated with normal development initially and with subsequent cognitive decline. These cases differ from those epilepsies with static intellectual disability. Copy number variants are an important source of gene mutation in neurocognitive disorders and the epilepsies.
The gene content of copy number variants found in 11 subjects with infantile spasms was involved in abnormalities of ventral forebrain development and pathways of synaptic function. [2]