Authors :
Presenting Author: JONSOO KIM, MD, PhD – Chungbuk National University Hospital
Hyewon Woo, MD – Chungbuk National University Hospital; Young Se Kwon, MD – School of Medicine, Inha University; Won Seop Kim, MD – College of Medicine, Chungbuk National University
Rationale:
Copy number variants (CNVs) play a still recognized role in the genetics of childhood-onset epilepsy. Epilepsy with pathologic CNVs is known to be accompanied by comorbid features. The aim of this retrospective study is to investigate the clinical features of epilepsy with pathologic CNVs.
Methods:
Of all children who underwent microarray analysis in the Chungbuk National University Hospital (Aug 2019 through Dec 2022) (n=181), we included 20 (11%) patients with childhood-onset epilepsy. All 20 patients had “epilepsy plus,” defined as epilepsy with comorbid features such as global developmental delay, intellectual disability, autistic spectrum disorder, and dysmorphic features. We investigated not only patients' demographics but also information related to epilepsy journey.Results:
The median age of 20 patients (7 boys, 13 girls) was 3.8 years (range 0.1-23.3 years). Most patients showed global developmental delay (95%), and 65% of them had two or more plus features. We found known clinically relevant pathogenic or likely pathogenic CNVs for epilepsy in five patients (25%). The phenotypes of them were compatible with the well-established diagnoses: 13q33-q34 deletion syndrome (MIM 619148), 16p11.2 deletion syndrome (MIM 611913, 2 patients), Xp11.23p11.22 duplication syndrome (MIM 300801), and ring chromosome of 18 syndrome. The phenotypic features of pathogenic CNV carriers were the eariler mean age of first seizure (4.0±5.1 vs 8.7±5.8 years) and the more pharmacoresistant (60% vs 33.3%) comparing to those of noncarriers, but statistically non-significant. And all pathogenic CNV carriers had at least one structural anomaly such as cerebral cortical malformation, renal anomaly, polydactyly, hemivertebrae, and cleft palate/lip.
Conclusions:
We indentified that children with epilepsy plus had a higher number of pathologic CNV carriers (25%), a younger onset of first seizure and poor drug response. Our results indicate that childhood-onset epilepsy with comorbid features, especially structural abnormalities, should be considered possibly pathogenic CNVs.
Funding: None