Background: Recently, a large number of monogenic causes of genetic epileptic encephalopathies
have been identified by high-throughput sequencing. Nevertheless, in up to 70% of
cases, a suspected genetic cause cannot be identified. Somatic mosaicism in epileptogenic
lesions (such as focal cortical dysplasia, hemimegalencephaly, polymicrogyria) may
explain some of these epilepsies.
Objectives: Analogous to the molecular genetic characterization of central nervous system (CNS)
tumors, the planned study should lead to an extension of the diagnostic work-up of
epileptogenic lesions and hereby to new therapeutic consequences.
Procedure:
1. Build a database on children who have undergone epileptic surgery in recent years.
2. Phenotyping of epilepsies and epileptogenic brain lesions.
3. Database analysis of prior knowledge in the field of somatic genetic alterations
in epilepsy. Comparison with experiences in the field of brain tumor research and
therapy.
4. Identification of lesions with therapeutic implications (genetic alterations as
“drug target”) and presentation of possible therapeutic approaches.
Methods: Description of the cohort of pediatric epilepsy patients who have undergone epilepsy
surgery. Identification of existing tissue samples and prioritization for epileptogenic
lesions. Literature research for “drug-targetable” genetic alterations. Transfer of
prior knowledge of oncological therapies in CNS tumors.
Results: In the past 10 years, 91 pediatric patients of the Heidelberg Epilepsy Center had
epilepsy surgery. The epileptogenic lesions are characterized and a diagnostic pathway
for the molecular genetic characterization of tissue is presented. “Drug-targetable”
lesions and potential pharmacological agents are presented together with analogous
developments in tumor biology.
Conclusion: The planned study as well as the results of the literature research show possibilities
for improvement in diagnostics, classification, and, in the long term, also therapy
of epileptogenic lesions and associated epileptic encephalopathies and developmental
disorders.
