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in cooperation with:
Fondazione Istituto Neurologico C. Besta IRCCS and
Venice International University

It has long been recognized that inheritance may play a role in causing epilepsy but only since mid twenties century, thanks to the work of Lennox and the Metrakos, some types of epilepsies that seemed mostly due to hereditary mechanisms have been identified. These epilepsies that “could not be ascribed to any other causative factors except a hereditary predisposition” were included in the category of idiopathic epilepsies in the ILAE classification of 1985. Since 1995, thanks to the impressive progresses of genetics and the development of new experimental strategies combining molecular biology with neurophysiological techniques, several genetically determined epilepsies have been characterized. Moreover the potential role of genetic factors among the multifactorial mechanisms responsible for epilepsies that are not primarily due to epilepsy gene mutations is nowadays being clarified.

These recent results challenge some concepts which the classification of epilepsy is based upon and have an important impact on the clinical practice as both the diagnostic and therapeutic approach.

The course is intended to provide neurologists, neuropaediatricians, paediatricians, medical geneticists, technicians and nurses with updated information on the genetics of the epilepsies. It will include a comprehensive account of the clinical picture of the genetic epilepsies discovered so far and on some new concepts about the genotype-phenotype correlation. Whereas in some cases the interpretation of the pathogenesis is straightforward in many others it needs to take into account the mediation of developmental or degenerative changes that are more or less directly genetically controlled. One important lesson we learned from the recent studies on genetics of epilepsies is the value of a multidisciplinary approach without which no progresses in the field would have been possible. Therefore the course has a multidisciplinary design as both the faculty and attendance composition to ensure the most effective interaction between people working in clinical and laboratory settings. Moreover to stimulate an interactive participation the students are invited to submit clinical cases relevant to the course topic that will be discussed in an ad hoc session.

A large group of lectures will be devoted to the systematic analysis of monogenic epilepsies with emphasis on epileptogenic channelopathies that are being intensively investigated in recent years.

Some of the most exciting genetic discoveries in the field have been made possible by a careful definition of the phenotype by clinical epileptologists. On the other hand epileptogenic gene mutations discovered by molecular biologists led to the recognition of previously unidentified clinical forms of epilepsy. From the theoretical point of view the information drawn from epileptogenic channelopathies gives us an insight in the mechanisms by which a mutation of a single gene, coding for an ion channel, can result in a complex epileptic phenotype. From the practical standpoint the genetic data made it possible the identification of previously unrecognized epilepsies and lead to reconsider the classification of epilepsies. Moreover they teach us that epileptogenic changes in excitable mechanisms may not solely depend on ion channel genes and that genes may influence neural excitability trough less direct but not less effective metabolic pathways.

Another session will deal with genetically determined brain maldevelopments responsible for epilepsies. Thanks to the sophisticated imaging techniques the responsibility of cerebral dysplasia in inducing epilepsies, previously defined as cryptogenic, is increasingly recognized. Several epileptogenic brain dysplasia are genetically determined and their knowledge is advancing our understanding of the role of genes in controlling normal and pathological brain development.

Furthermore a session will be devoted to genetically determined degenerative disorders associated to epilepsy whose prototypes are Progressive Myoclonus Epilepsies (PMEs) and namely Lafora and Unwerricht-Lundborg diseases. Neurodegeneration is observed in several types of epilepsies, the information drawn from PMEs can be particularly helpful to understand the reciprocal cause- effect relationships between degenerative and the influence of genetic factors.

These three sections will be preceded by a group of lectures introducing the general concepts and methods and followed by a concluding session during which the potential interest of genetic concepts in designing new therapeutic strategies will be discussed.

In designing the program a particular effort has been devoted in keeping it strictly adherent to the interest of people who are dealing with epilepsy in their daily practice, granting, at the same time, the highest quality of the scientific information. The outstanding level of the faculty, which includes some distinguished foreign guests who greatly contributed in the recent advances in the field, makes us confident in fulfilling this goal.