Affiliations: Department of Neuropediatrics, University Medical Center Schleswig-Holstein (UKSH), Kiel Campus, Germany
Note: [] Corresponding author: Ingo Helbig, Department of Neuropediatrics, University Medical Center Schleswig-Holstein (UKSH), Arnold-Heller-Str. 3, Haus 9, 24105 Kiel, Germany. Tel.: +49 431 597 1761; Fax: +49 431 597 1769; E-mail: [email protected].
Abstract: Structural genomic variations, gains or losses of chromosomal material, are increasingly recognized in human health and disease and represent a major source of interindividual genetic variation. In seizure disorders, structural genomic variations are important on at least three different scales, ranging from (1) chromosomal disorders or gross chromosomal rearrangements, (2) genomic disorders and rare microdeletions and microduplications, to (3) small deletions and duplications of known epilepsy candidate genes. While structural genomic variations in known epilepsy candidate genes such as SCN1A and chromosomal disorders are both rare, possibly pathogenic microdeletions and microduplications can be identified in up to 10% of patients with seizure disorders. This review aims to provide an overview of the different classes of structural genomic variants pertaining to the epilepsies, guide the clinician in interpreting these variants and discuss the lessons learned from structural genomic variants for future genetic technologies. Particular reference will be paid to the phenotypes of the frequently encountered 15q13.3 and 16p13.11 microdeletions, as these variants may pose a challenge in clinical practice.
