Epileptic seizures and chromosomal microdeletions/duplications

Aims: Recent estimates suggest that pediatric epilepsies are caused by chromosomal microdeletions and/or duplications in approximately 5 to 15% of patients. Here, we report the results of molecular karyotyping in 43 children with various patterns of epileptic seizures to find epilepsy-related micro-rearrangements.

Methods: Patient inclusion criteria were unexplained epilepsy, intellectual disability, minor dysmorphism, unremarkable screening for metabolic and infectious disorders, and a normal pregnancy and delivery history. The analyses were performed with Illumina Infinium Human1 M-DuoV1 arrays.

Results: In 3 out of 43 patients (7%), we found likely causative de novo CNVs: a 3.4-Mb deletion in 1q41q42.12 in an 11-year-old girl, an 834-kb deletion in 19p13.2 in a 6-year-old boy, and a mosaic two-part duplication of 218 kb in 17p13.2 and 422 kb in 17p13.1 in a 20-year-old man. All three presented with nonclassified generalized epilepsy. Six additional patients showed chromosomal variants (a deletion in one and distinct duplications in five patients) with possible but uncertain pathogenic relevance. These aberrations included a paternally inherited duplication in 15q13.3 in a 6-year-old girl with Lennox-Gastaut syndrome.

Conclusion: Our study revealed one new epilepsy-related region on chromosome 19p13.2. Furthermore, we found duplication in 15q13.3 in one patient and her healthy father. Deletions in this region are associated with epilepsy; however, duplications are reported in healthy people as well as patients with various neuropsychiatric and neurological disorders, but to date, in only one patient with seizures. Thus, the duplication in our patient is an additional hint toward a possible relevance of this duplication for epilepsy.

In total, causative chromosomal micro-rearrangements were detected in at least 3 of 43 patients (7%) with epilepsy and intellectual disability. Our data further emphasize the power of DNA-arrays in revealing disease-related genetic regions and thus elucidating the cause for previously unexplained epilepsies.