Abstracts

Rationale: Idiopathic generalised epilepsies (IGEs) have a predominant genetic aetiology and account for 30% of all epilepsies. A 15q13.3 microdeletion associated with a spectrum of neuropsychiatric disorders also increases risk for IGE. Five additional recurrent microdeletions are also found in excess in neuropsychiatric disorders. This study investigates whether these six microdeletions predispose to common IGE syndromes. Methods: Six large (>400 kb) recurrent microdeletions at 1q21.1, 15q11.2, 15q13.3, 16p11.2, 16p13.11, and 22q11.2 were assessed by Affymetrix SNP 6.0 arrays in 1104 IGE patients from North-Western Europe and 3022 population controls. All microdeletions were validated by quantitative PCR and their breakpoints determined by array comparative genomic hybridisation. Results: In total, 31 IGE patients (2.8%) carried a candidate microdeletion compared to nine controls (0.3%; OR=9.7, 95% CI: 4.6-20.4, p=3.2x10-13). Microdeletions at 15q11.2 (n=12), 15q13.3 (n=10) and 16p13.11 (n=5) were the most frequent deletions in the IGE patients. While most (11/15) microdeletions were inherited, four de novo microdeletions were found at 15q13.3, 16p13.11 and 22q11.21. Most IGE patients carrying a deletion had characteristic IGE phenotypes without obvious intellectual deficits or psychiatric disorders. Conclusions: Our study suggests that rare recurrent microdeletions collectively account for a significant fraction of the genetic aetiology of common IGE syndromes. The present findings expand the channelopathy concept of IGE and support the role of neurodevelopmental processes in epileptogenesis.