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. 2014 Jun;75(6):943-58.
doi: 10.1002/ana.24178. Epub 2014 Jun 13.

Copy number variation plays an important role in clinical epilepsy

Heather Olson  1 , Yiping Shen, Jennifer Avallone, Beth R Sheidley, Rebecca Pinsky, Ann M Bergin, Gerard T Berry, Frank H Duffy, Yaman Eksioglu, David J Harris, Fuki M Hisama, Eugenia Ho, Mira Irons, Christina M Jacobsen, Philip James, Sanjeev Kothare, Omar Khwaja, Jonathan Lipton, Tobias Loddenkemper, Jennifer Markowitz, Kiran Maski, J Thomas Megerian, Edward Neilan, Peter C Raffalli, Michael Robbins, Amy Roberts, Eugene Roe, Caitlin Rollins, Mustafa Sahin, Dean Sarco, Alison Schonwald, Sharon E Smith, Janet Soul, Joan M Stoler, Masanori Takeoka, Wen-Han Tan, Alcy R Torres, Peter Tsai, David K Urion, Laura Weissman, Robert Wolff, Bai-Lin Wu, David T Miller, Annapurna Poduri
Affiliations

Copy number variation plays an important role in clinical epilepsy

Heather Olson et al. Ann Neurol. 2014 Jun.

Abstract

Objective: To evaluate the role of copy number abnormalities detectable using chromosomal microarray (CMA) testing in patients with epilepsy at a tertiary care center.

Methods: We identified patients with International Classification of Diseases, ninth revision (ICD-9) codes for epilepsy or seizures and clinical CMA testing performed between October 2006 and February 2011 at Boston Children's Hospital. We reviewed medical records and included patients who met criteria for epilepsy. We phenotypically characterized patients with epilepsy-associated abnormalities on CMA.

Results: Of 973 patients who had CMA and ICD-9 codes for epilepsy or seizures, 805 patients satisfied criteria for epilepsy. We observed 437 copy number variants (CNVs) in 323 patients (1-4 per patient), including 185 (42%) deletions and 252 (58%) duplications. Forty (9%) were confirmed de novo, 186 (43%) were inherited, and parental data were unavailable for 211 (48%). Excluding full chromosome trisomies, CNV size ranged from 18kb to 142Mb, and 34% were >500kb. In at least 40 cases (5%), the epilepsy phenotype was explained by a CNV, including 29 patients with epilepsy-associated syndromes and 11 with likely disease-associated CNVs involving epilepsy genes or "hotspots." We observed numerous recurrent CNVs including 10 involving loss or gain of Xp22.31, a region described in patients with and without epilepsy.

Interpretation: Copy number abnormalities play an important role in patients with epilepsy. Because the diagnostic yield of CMA for epilepsy patients is similar to the yield in autism spectrum disorders and in prenatal diagnosis, for which published guidelines recommend testing with CMA, we recommend the implementation of CMA in the evaluation of unexplained epilepsy.

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Figures

Figure 1
Figure 1
Flowchart of patient selection and chromosomal microarray genotype results
Figure 2
Figure 2
Pie chart of CNV sizes in our cohort.
Figure 3
Figure 3
Regions of overlapping CNVs in our series, not including known epilepsy genes, syndromes involving epilepsy, or epilepsy “hot spots.”
Figure 4
Figure 4
Cases with epilepsy and deletions involving Xp22.31 in our October 2006 - August 2012 series, in the literature, and in the Decipher database.
See this image and copyright information in PMC

Comment in

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