Genotyping and phenotyping epilepsies of childhood

Epilepsy occurs in 1 to 2 of 100 children. The underlying etiology and clinical symptoms can be very variable. This has an impact on the treatment and prognosis of epilepsy. In the last few years, many new genes have been discovered that play a role in the development of epilepsy. Therefore, in patients with epilepsy, the underlying cause can be more often identified. However, the precise yield of genetic testing and the clinical symptoms that can occur in patients with a variant in one of the epilepsy genes is yet unknown.With this research, we showed that genetic research is important, both diagnostically and psychologically. We were able to describe the clinical symptoms for a number of genetics forms of epilepsy (related to the genes SYNGAP1, GRIN2A, PCDH19, STX1B and PRRT2). These studies help us to recognize these genetic forms of epilepsy. Early recognition and treatment of these disorders and their symptoms is important to improve outcome. We also found that different variants in the GRIN2A-gene results in a different clinical effect. This finding is a first step towards developing new, targeted therapies for GRIN2A-related epilepsy, dependent on the results of genetic testing.In conclusion, this thesis has led to more knowledge about genetic epilepsies on a diagnostic, therapeutic and psychological level. We have bundled these results with our experiences in clinical practice into a proposal for a new diagnostic algorithm for genetic testing in patients with epilepsy