Genetic Testing on Epilepsies with Reflex Seizures

Abstract Reflex seizures occur in a broad range of epilepsies, including common epilepsies such as idiopathic (or genetic) generalized epilepsies, and more rare epilepsy syndromes such as progressive myoclonic epilepsies and other monogenic conditions. Idiopathic generalized epilepsies have a polygenic basis, with multiple gene variants contributing to the disorder—but in the typical idiopathic generalized epilepsy clinical presentation, no diagnostic genetic test is indicated. However, several monogenic conditions have been recognized in recent years, with intellectual disability and generalized and reflex seizures, which need be differentiated from the idiopathic generalized epilepsies. Rare epilepsy syndromes include conditions caused by chromosomal abnormalities (e.g., trisomy 21), copy number variants, or single gene abnormalities (e.g., progressive myoclonic epilepsies, familial adult myoclonic epilepsy, Dravet syndrome, others with photosensitivity, or other reflex seizures caused by pathogenic varints in CACNA1A, CDKL5, CHD2, GNAO1, LGI1, NEXMIF, NOVA2, MECP2, PURA, RORB, SYN1, SYNGAP1). These genetic syndromes featuring reflex seizures are at times identified based on their electroclinical characteristics, but need be confirmed by specific genetic testing, ranging from karyotyping, chromosomal microarray analysis, direct Sanger sequencing of the target gene, next-generation sequencing panels of epilepsy genes, trio-based whole exome, or genome sequencing. Although the choice of the most appropriate genetic testing is based on the clinical presentation, it is not uncommon for wide-spectrum genetic testing to reveal an underlying abnormality in patients with reflex seizures, even when their characteristics do not suggest a specific genetic etiology.