Clinical epidemiology of newly diagnosed early life epilepsy: underlying causes and contributions from genetics.
Abstract number :
1.085
Submission category :
4. Clinical Epilepsy
Year :
2015
Submission ID :
2312774
Source :
www.aesnet.org
Presentation date :
12/5/2015 12:00:00 AM
Published date :
Nov 13, 2015, 12:43 PM
Authors :
Anne Berg, John Mytinger, Kelly G. Knupp, Renee Shellhaas, Tobias Loddenkemper, Russell Saneto, William D. Gaillard, Joseph Sullivan, Zachary Grinspan, Catherine Chu, Cynthia Keator, Courtney Wusthoff, Jason Coryell, Elaine Wirrell, Adam Hartman, Nicole R
Rationale: Early life epilepsies (ELE) comprise numerous rare forms of epilepsy secondary to a large number of recognizable causes. Many of these have genetic bases which in turn may have therapeutic implications. We provide a contemporary assessment of the clinical epidemiology of newly diagnosed ELE and emphasize the causes and contributions of genetic testing.Methods: Children with newly diagnosed ELE (onset <3y) were prospectively recruited at 17 US pediatric epilepsy centers (2012-2015). Clinical data from initial diagnostic evaluations were extracted from medical records, entered in a REDCAP© database and analyzed with standard methods. All procedures were approved by all institutional IRBs.Results: Of the first 620 children enrolled, 317, (51%) were boys, average onset age=10.9m (SD=9.4), and average diagnosis age=12.4m (SD=9.9). The epilepsy diagnosis was West syndrome (WS) in 191 (30.8%). Of non-WS epilepsies, 40 (6.5%) had other specific epilepsy syndromes and 389 (62.7%) had nonsyndromic epilepsies (NSE). Neuroimaging (mostly seizure protocol MRI) was performed in 449 (72%): 77% in WS and 70% in Non-WS epilepsies (p=0.06). Some form of genetic testing was done in 222 (36%) including 55% in WS and 38% in non-WS groups (p<0.0001). Genetic testing was done prior to epilepsy presentation in 77, as part of the epilepsy evaluation in 75, and both in 70. Overall, a specific underlying cause was identified in 255 (41%): 58% in WS and 34% in non-WS groups (p<0.0001). Acquired insults were diagnosed in 74 (12%) children (18 HIE, 7 infectious, 24 IVH, and 25 other). Causes with a known or potentially genetic basis included cortical malformations (CM, N=48), other developmental brain conditions (DBC, N=27), neurocutaneous (NC, N=25), metabolic (N=10), and genetic (N=68) conditions/epilepsies. 82 children had genetic confirmation of the underlying cause including 2 CM, 2 DBC, 8 NC, 6 metabolic, and 64 genetic conditions/epilepsies. Variants of unknown significance (VUS) were reported in 31 (5%) of children, and 12 children had genetic disorders clinically diagnosed only (most TSC). When a cause was identified, there was genetic confirmation of the cause in 36% of WS and 29% of non-WS groups (p=0.21). The yield for pathogenic variants was >
Clinical Epilepsy