Facilitators
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Rikke Steensbjerre Møller, Professor
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Elena Gardella, Clinical Associate Professor
Description
Epilepsy is one of the most common neurological disorders with more than 50 million people affected worldwide. Epilepsy is a spectrum disorder characterized by recurrent and spontaneous epileptic seizures caused by abnormal excessive or synchronous neuronal activity of the brain. The epilepsy syndrome classifications are important for a proper management and this is only possible based on combined clinico-EEG manifestations. Even the simple differentiation between focal and generalized epilepsies might be difficult without an EEG even by an experienced epileptologist. Within the group of childhood onset epilepsies, epileptic encephalopathies account for a substantial proportion of the most severe and refractory epilepsies. Epileptic encephalopathies are defined as syndromes in which seizures or the epileptiform activity contribute to, or exacerbate the underlying brain dysfunction. The clinical picture is often complicated by comorbidities including intellectual disability, behavioral problems, movement disorders and autism.
During the last decade, next-generation sequencing (targeted gene panels or whole-exome sequencing) has led to a virtual explosion of gene discovery, raising the number of bona fide genes and possible candidate genes for monogenic epilepsies to more than 400 genes, explaining 20-25% of all cases with severe early-onset epilepsies that had otherwise no identifiable causes. Finding a genetic cause is of pronounced importance for both the patient, the family and professional caretakers. Knowing the etiology can help ensuring the right support and treatment, knowledge about prognosis and recurrence risk and removal of guilt etc. Furthermore, knowing the pathophysiological mechanisms may allow us to develop more effective treatments that can be targeted to the individual patient based on his/her genetic profile instead of empiric trials of medications broadly indicated for epilepsy. Monogenic epilepsies offer an excellent opportunity to achieve targeted treatments (precision medicine), mainly because of the ongoing explosion in gene discovery, the existence of good animal and in vitro models, in which targeted medications can be developed, and the ability to assess the efficacy of experimental targeted treatments in small clinical trials.
In our team pediatricians, neurologists, neurophysiologists, geneticists and basic scientists work together on projects including:
Gene discovery in neurodevelopmental disorders and epilepsy by the use of next generation sequencing (whole exome sequencing or targeted arrays).
Genotype-phenotype correlation studies, including electro-clinical characterization of genetic epilepsy syndromes, functional studies of selected mutations in cell systems, and evaluation of treatment response.