Laurent Villard

31 mars 2017

Génétique Médicale et Génomique Fonctionnelle - INSERM UMR_S 910 - Faculté de Médecine de La Timone, Marseille

Genetics and pathophysiology of early onset epileptic encephalopathies

invité par Frédéric Brocard


Abstract :

Our team has been interested for a few years in a group of rare epilepsies, called early onset epileptic encephalopathies (EEP). In this group, we focus on those with a suppression-burst EEG (EEP-SB), or Ohtahara syndrome. This type of epilepsy is characterized by : 1- onset within the first weeks of life ; 2- clinical manifestations resulting in erratic myoclonus, spasms and/or quasi-continuous partial seizures ; 3- a suppression burst EEG ; 4- a severe clinical evolution with a high mortality during the first years of life ; 5- an absence of effective treatment, in particular of conventional antiepileptics. The vast majority of cases are sporadic, implying that the incidence of the disease will not change. We have created a cohort of more than 500 EEP patients, in collaboration with several pediatric neurology services. It was recently shown that there is a strong genetic basis for these pathologies. Thanks to new high-throughput sequencing technologies, we now propose a search for a genetic anomaly in nearly 100 genes involved in genetic epilepsies, which allowed us to identify a genetic cause in 120 cases. These results revealed that the KCNQ2 gene (potassium channel subunit / IM current) is the most frequently mutated gene in our cohort. This finding is unexpected because mutations in the KCNQ2 gene are traditionally found in patients with benign familial neonatal seizures (BFNS). The fact that mutations in the same gene cause very severe clinical pictures led us to study the pathophysiology of EEPs related to mutations of KCNQ2. This seminar will present our strategy to study genetic epilepsies and our results.

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