Copy number variations in children with brain malformations and refractory epilepsy

Am J Med Genet A. 2015 Mar;167A(3):512-23. doi: 10.1002/ajmg.a.36886.


Brain malformations are a major cause of therapy-refractory epilepsy as well as neurological and developmental disabilities in children. This study examined the frequency and the nature of copy number variations among children with structural brain malformations and refractory epilepsy. The medical records of all children born between 1990 and 2009 in the epilepsy registry at the Astrid Lindgren's Children's Hospital were reviewed and 86 patients with refractory epilepsy and various brain malformations were identified. Array-CGH analysis was performed in 76 of the patients. Pathogenic copy number variations were detected in seven children (9.2%). In addition, rearrangements of unclear significance, but possibly pathogenic, were detected in 11 (14.5%) individuals. In 37 (48.7%) patients likely benign, but previously unreported, copy number variants were detected. Thus, a large proportion of our patients had at least one rare copy number variant. Our results suggest that array-CGH should be considered as a first line genetic test for children with cerebral malformations and refractory epilepsy unless there is a strong evidence for a specific monogenic syndrome.

Keywords: CNV; array-CGH; brain malformation; epilepsy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Brain / abnormalities*
  • Child, Preschool
  • Chromosome Aberrations
  • Comorbidity
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations*
  • Epilepsy / diagnosis*
  • Epilepsy / diagnostic imaging
  • Epilepsy / genetics*
  • Female
  • Genetic Association Studies
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Male
  • Radiography