PDE enzymes catalyze the hydrolysis of cAMP and cGMP, two key second messengers modulating a variety of neuronal pathways.49,50 Lastly, a noteworthy finding was the RYR2 gene associated with GGE, which was identified by combining rare and common genetic variation, representing an example of convergent epilepsy generic risk across the allele frequency spectrum. This evidence concerns the gene RYR2 and epilepsy.