The genetic generalized epilepsies (GGEs) are mainly genetically determined disorders. Although inheritance in most cases appears to be complex, involving multiple genes, variants of a number of genes are known to contribute. Pathogenic variants of SLC2A1 leading to autosomal-dominant GLUT1 deficiency account for up to 1% of cases, increasing to 10% of those with absence seizures starting before age 4 years. Copy number variants are found in around 3% of cases, acting as risk alleles. Copy number variation is much more common in those with comorbid learning disability. Common variant associations are starting to emerge from genome-wide association studies but do not yet explain a large proportion of GGEs.
Although currently genetic testing is not likely to yield a diagnosis for most patients with GGEs, it can be of great importance in specific clinical situations. Providers should consider the individual patient’s history in determining the utility of genetic testing.