Epilepsy & Behavior 41 (2014) 276
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Editorial
Thinking about cognition and epilepsy Global cognitive function is considered subnormal in at least onequarter of children with epilepsy [1]. Understanding the factors that contribute to cognitive dysfunction in epilepsy could lead to improved therapies and outcomes for affected individuals. However, studying the factors that contribute to cognitive deficits in epilepsy is complicated. Certainly, severity and duration of seizures may contribute. In epileptic encephalopathy syndromes, most patients suffer from intractable seizures and developmental regression or delays, which are probably both due primarily to the same, single genetic mutation. Another factor that may influence outcomes is long-term exposure to antiepileptic drugs [2]. Genetics certainly plays an important role as well, and advances in genomics over the past decade have made it possible to begin to perform systematic investigations. In this issue of Epilepsy & Behavior, Busch and colleagues present a Targeted Review of the current state of our understanding of the genetics of cognition in epilepsy. This elegant summary of the literature provides an overview of the role of genetics in cognition generally and then presents the current knowledge and challenges for understanding how genetics influences cognitive outcome in patients with epilepsy. The takehome message? This is a complicated problem that deserves further study. First, there is no single gene for cognition. Rather, there are likely many genetic variants, which could be rare or common, that influence cognition. Despite numerous genome-wide association studies, there are only a handful of genes with consistent findings regarding their role in cognition; examples discussed are BDNF, APOE, and COMT. Syndromic forms of epilepsy provide some insight into the genetics of cognition in epilepsy, as cognitive delays and seizures tend to cooccur. However, even among syndromes such as tuberous sclerosis, outcomes are variable. Our own studies of copy number variants in epilepsy reveal shared genetic susceptibility to intellectual disability, epilepsy, and related disorders [3]. Individuals with generalized epilepsy and cognitive deficits are much more likely to harbor a deletion than patients with normal intellect, but the specific factors influencing outcome – whether detrimental or protective – are unknown. Clearly, there are many questions yet to be answered. New approaches and large, well-phenotyped cohorts are required to better
http://dx.doi.org/10.1016/j.yebeh.2014.09.007 1525-5050/© 2014 Elsevier Inc. All rights reserved.
understand the genetic relationship between epilepsy and cognition. Do the same genetic factors that determine cognitive ability in unaffected individuals play a role in cognitive dysfunction in epilepsy? Are there protective genetic factors that preserve intellectual functioning in some patients? As the authors note, a better understanding of the genetics of cognition and epilepsy may very well benefit patients with a wider range of neurodevelopmental disorders including autism spectrum disorders and ADHD, making the need to move the field forward even more pressing. Acknowledgments Dr. Mefford's research is funded by the NIH/NINDS (grant NS068605) and the Burroughs Wellcome Fund. (grant 1007607) Conflict of interest Dr. Mefford has no conflicts of interest to declare. References [1] Berg AT, Langfitt JT, Testa FM, Levy SR, DiMario F, Westerveld M, et al. Global cognitive function in children with epilepsy: a community-based study. Epilepsia 2008;49: 608–14. [2] Ijff DM, Aldenkamp AP. Cognitive side-effects of antiepileptic drugs in children. Handb Clin Neurol 2013;111:707–18. [3] Mullen SA, Carvill GL, Bellows S, Bayly MA, Trucks H, Lal D, et al. Copy number variants are frequent in genetic generalized epilepsy with intellectual disability. Neurology 2013;81:1507–14.
Heather C. Mefford Department of Pediatrics, Division of Genetic Medicine, University of Washington, USA E-mail address: [email protected].
Contents lists available at ScienceDirect
Epilepsy & Behavior journal homepage: www.elsevier.com/locate/yebeh
Editorial
Thinking about cognition and epilepsy Global cognitive function is considered subnormal in at least onequarter of children with epilepsy [1]. Understanding the factors that contribute to cognitive dysfunction in epilepsy could lead to improved therapies and outcomes for affected individuals. However, studying the factors that contribute to cognitive deficits in epilepsy is complicated. Certainly, severity and duration of seizures may contribute. In epileptic encephalopathy syndromes, most patients suffer from intractable seizures and developmental regression or delays, which are probably both due primarily to the same, single genetic mutation. Another factor that may influence outcomes is long-term exposure to antiepileptic drugs [2]. Genetics certainly plays an important role as well, and advances in genomics over the past decade have made it possible to begin to perform systematic investigations. In this issue of Epilepsy & Behavior, Busch and colleagues present a Targeted Review of the current state of our understanding of the genetics of cognition in epilepsy. This elegant summary of the literature provides an overview of the role of genetics in cognition generally and then presents the current knowledge and challenges for understanding how genetics influences cognitive outcome in patients with epilepsy. The takehome message? This is a complicated problem that deserves further study. First, there is no single gene for cognition. Rather, there are likely many genetic variants, which could be rare or common, that influence cognition. Despite numerous genome-wide association studies, there are only a handful of genes with consistent findings regarding their role in cognition; examples discussed are BDNF, APOE, and COMT. Syndromic forms of epilepsy provide some insight into the genetics of cognition in epilepsy, as cognitive delays and seizures tend to cooccur. However, even among syndromes such as tuberous sclerosis, outcomes are variable. Our own studies of copy number variants in epilepsy reveal shared genetic susceptibility to intellectual disability, epilepsy, and related disorders [3]. Individuals with generalized epilepsy and cognitive deficits are much more likely to harbor a deletion than patients with normal intellect, but the specific factors influencing outcome – whether detrimental or protective – are unknown. Clearly, there are many questions yet to be answered. New approaches and large, well-phenotyped cohorts are required to better
http://dx.doi.org/10.1016/j.yebeh.2014.09.007 1525-5050/© 2014 Elsevier Inc. All rights reserved.
understand the genetic relationship between epilepsy and cognition. Do the same genetic factors that determine cognitive ability in unaffected individuals play a role in cognitive dysfunction in epilepsy? Are there protective genetic factors that preserve intellectual functioning in some patients? As the authors note, a better understanding of the genetics of cognition and epilepsy may very well benefit patients with a wider range of neurodevelopmental disorders including autism spectrum disorders and ADHD, making the need to move the field forward even more pressing. Acknowledgments Dr. Mefford's research is funded by the NIH/NINDS (grant NS068605) and the Burroughs Wellcome Fund. (grant 1007607) Conflict of interest Dr. Mefford has no conflicts of interest to declare. References [1] Berg AT, Langfitt JT, Testa FM, Levy SR, DiMario F, Westerveld M, et al. Global cognitive function in children with epilepsy: a community-based study. Epilepsia 2008;49: 608–14. [2] Ijff DM, Aldenkamp AP. Cognitive side-effects of antiepileptic drugs in children. Handb Clin Neurol 2013;111:707–18. [3] Mullen SA, Carvill GL, Bellows S, Bayly MA, Trucks H, Lal D, et al. Copy number variants are frequent in genetic generalized epilepsy with intellectual disability. Neurology 2013;81:1507–14.
Heather C. Mefford Department of Pediatrics, Division of Genetic Medicine, University of Washington, USA E-mail address: [email protected].
