Copy Number Variants are Frequent in Genetic Generalized Epilepsy with Intellectual Disability

Copy number variants, a genetic abnormality, contribute to the cause of multiple neurodevelopmental disorders with complex inheritance including generalized epilepsy of a genetic underpinning and intellectual disability. In the October 21, 2013, issue of the journal Neurology, Drs. Mullen and investigators from the Florey Institute of Neurosciences and Mental Health and the Epilepsy Research Center in Australia present a study where they examined whether copy number variants were more common in those with a combination of intellectual disability and genetic generalized epilepsy than in those with either phenotype alone via a case-controlled study.

• The study screened 359 probands with generalized genetic epilepsy and 60 probands with intellectual delay and generalized genetic epilepsy for generalized genetic epilepsy associated recurrent microdeletions at chromosomes 15k13.3, 15q11.2, and 16p13.11 via quantitative PCR.
• The results showed:
  • Individuals who had intellectual developmental delay and generalized genetic epilepsy showed a higher rate of copy number variants compared with probands with generalized genetic epilepsy alone, with 17 of 60 intellectually delayed and genetic generalized epilepsy probands having one or more potentially causative copy number variants.
  • Patients with intellectual delay and generalized genetic epilepsy had a three-fold higher rate of these three generalized genetic epilepsy-associated recurrent microdeletions than probands with genetic generalized epilepsy alone.
• The investigators concluded that copy number variants are common in those individuals with intellectual delay and generalized genetic epilepsy with recurrent deletions at 15q13.3, 15q11.2, and 16p13.11, particularly enriched compared with individuals with generalized genetic epilepsy or intellectual delay alone.
• Testing for copy number variants in patients with genetic generalized epilepsy and intellectual delay should yield a high diagnostic result in a clinical setting and help inform genetic counseling.