League Against Epilepsy
Commission on Genetics
Date: January, 2003
Report By: Jeffrey Noebels, M.D., Ph.D., Chair
Elving Anderson, USA
Samuel Berkovic, Australia
Olivier Dulac, France
Mogens Friis, Denmark
Mark Gardiner, Great Britain
Shinichi Hirose, Japan
Satish Jain, India
Dick Lindhout , Netherlands
Iscia Lopes-Cendes, Brazil
Jeffrey Noebels, USA
Ruth Ottman, USA
Alejandro Scaramelli, Uruguay
Jose Serratosa, Spain
Ortrud Steinlein, Germany
Federico Zara, Italy
To advise the ILAE executive on ways to support the international
search for genes that raise the risk of epilepsy, to encourage genetic
research that can improve epilepsy diagnosis and therapy, and to
educate clinicians, individuals with epilepsy, and their families
about genetic advances in epilepsy.
- To organize the search for human epilepsy genes on a worldwide
scale through broad participation by members of ILAE chapters.
- To prioritize complex epilepsies suitable for multicenter collaborative
gene mapping studies.
- To make the results of genetic research on the epilepsies readily
accessible to clinicians.
- To improve the public understanding of genetic factors in epilepsy.
- To work with related ILAE commissions to increase understanding
of newly identified genes and their role in basic mechanisms of
epileptogenesis and anti-epileptogenesis.
Summary of Activities for 2002
Workshop on Complex Genetic Epilepsies
In prior years our commission has emphasized the search for large
families that have a number of relatives with epilepsy. This approach
has led to the identification of more than 20 specific genes in
which a mutation is linked to the pathogenesis of epilepsy. Many
of the more common epilepsies, however, show an increased risk for
epilepsy but at a level that does not fit a simple mode of inheritance.
In the fall of 2000 a commission task force (Anderson, Berkovic,
Gardiner, Leppert, Ottman, Noebels) initiated plans for a workshop
dealing with this problem, and the Commission organized the 2 day
workshop over the last year.
The workshop, “Molecular Analysis of Complex Genetic Epilepsies”
was convened in Bethesda, MD on January 30-February 1, 2002. Major
additional funding was provided by NIH/NINDS, with additional support
from the American Epilepsy Society and from the ILAE Commission
on the Search for Epilepsy Genes.
Forty clinicians and scientists from a dozen countries discussed
epilepsy in terms of its classification, epidemiology, evidence
for genetic etiology, neurobiology, phenotype/genotype correlations,
and the use of linkage and association studies to identify genes
that contribute to the susceptibility for epilepsy. The ultimate
goal is to understand the underlying pathogenetic mechanisms and
thus help to develop genomics-based means of intervention and therapy.
In a final session the participants discussed strategies for developing
large-scale collaborative efforts to identify families, collect
DNA samples, and analyze the data using molecular and statistical
methods. The priority setting for specific phenotypes, as well as
the timing and coordination of the efforts that would be required
for such a large-scale research undertaking have not been fully
established. The commission will continue to discuss the advantages
and obstacles to a world wide collaborative project during the coming
A full length report of this workshop appeared in Epilepsia
Commission Meeting at the European Epilepsy Congress in Madrid,
The Commission met again at the European Epilepsy Congress in Madrid.
Proposals for several project were reviewed, including:
- Formation of an International Consortium on Idiopathic Inherited
- Implementation of the Genetics Commission Website, featuring
descriptions of defined clinical genetic epilepsy syndromes, as
well as lists of genetic epilepsy specialists by country
- A classification scheme of genetic epilepsies to be submitted
to the ILAE Classification Committee for further consideration,
- Formulation of proposal for a Genetics Program at the Tunis
meeting, tentatively entitled “Genetic Research in Mediterranean
There is a continuing effort to implement specific projects previously
represented on the Commission, including malformations, pregnancy,
teratogenetics, and genetic counseling. This may involve a recommendation
to the Executive Committee in the coming year for creation of a
new commission or subcommissions.
Future Activities for 2003
Interaction with other ILAE Commissions
The Genetics Commission is working closely with the Commission
on Classification of the Epilepsies to ensure an authoritative integration
of specific categories of inherited epilepsy into the classification
scheme. This work will be published on the website.
Interaction with ILAE Chapters
Thirty chapters (29 ILAE and one IBE) have designated representatives
to the Gene Search Program. These responses can provide opportunities
for cooperation among neighboring chapters and also partnerships
between developed and developing countries. The participants will
be listed on the new website in the coming year.
Regional Workshops on the Search for Epilepsy Genes
In many countries there are families with new genes for epilepsy
waiting to be identified. ILAE chapters can play a critical role
by encouraging a nation-wide perspective for this search process.
Each chapter that becomes involved can benefit from the experience
in neighboring countries, and here the broad ILAE regional pattern
provides a further advantage. In the year 2002, commission members
made themselves available for didactic sessions organized at two
regional meetings, including the AOEC (4th Asian and
Oceanian Epilepsy Congress), Nagano, Sept. 11-14 (Organizers: S.
Jain, S. Berkovic, T.Yamauchi), and the.Joint Congress of ICNA (9th
International Child Neurology Congress) and AOCNA (7th Asian and
Oceanic Congress of Child Neurology), Beijing, Sept. 20-25, 2002
(Organizers: J. Noebels, S. Jain, X-R Wu). These workshops are intended
for chapter representatives and others who wish to take an active
role in finding such families with epilepsy that would be informative
for gene mapping.
In anticipation of the ILAE Congress to be held in Tunisia in 2003,
a task force will develop a workshop and specific participation
of chapters in Northern Africa in the Gene Search mapping project.
The general topic will be the subject of a symposium organized by
the Genetics Commission for the ILAE Congress in Tunis entitled
“Genetic Epilepsy Research in Mediterranean Countries”.
A questionnaire on the effectiveness of various educational modalities
was circulated to the chapters, and the responses analyzed. A short
report summarizing these responses and other major issues in patient
education about epilepsy genetics will be prepared for the Website.
This topic will be considered further in a symposium at the ILAE
Congress in Tunis sponsored by the Genetics Commission and organized
by E. Andermann that will focus on genetic counseling in epilepsy.
This group met following the NIH workshop in February 2002 and
is preparing a report outlining the clinical criteria that would
be employed as the collaborative project documents families in preparation
for DNA analysis. Ad hoc members of this group were: Elving Anderson,
Olivier Dulac, Mark Gardiner Allen Hauser, Mark Leppert, Ruth Ottman,
and Thomas Sander.
The objective of this subcommission is to describe the utility
of what we currently know about epilepsy genes and to develop guidelines
on how to correctly apply available knowledge. A report describing
diagnostic, prognostic and therapeutic implications has been generated
by the working group (J. Serratosa, S. Berkovic, M. Gardiner, D.
Lindhout, A. Lehesjoki, and E. Anderson) and will be available on
the commission website.
This subcommission will collaborate with the Neurobiology Commission
in supporting relevant speakers for the forthcoming 2003 WONOEP
meeting to be held in Tunisia. In addition, a scientific plenary
symposium at the 25th ILAE Congress has been organized
on the topic of “Epilepsy Research in the Postgenomic Era” (Organizers:
J. Noebels, J. Chelly). This topic will feature new genetic discoveries
leading to inherited defects in brain inhibitory mechanisms and
A working group has been established to develop an Internet website
for international education on epilepsy genes. The major focus will
be information for clinicians, listing epilepsy genes discovered
to date, and lists of genetic specialists by country. Links to other
sources of information will be provided, including the diagnostic
phenotypes, appropriate uses of genetic testing, and genetic counseling
information. The editorial board for this project includes Jeff
Noebels, Sam Berkovic, Jose Serratosa, and Elving Anderson. The
new website will be hosted by the ILAE, and should be established
in 2003. A template has been designed for the database, and editors
have been assigned genes for annotation and publication on the web.
The editorial board of the Commission will be responsible for maintaining
accuracy and up to date information.
Based on discussions at the Commission meeting, work groups are
being formed to maximize the effective expertise of the Commission.
A high priority will be assigned to increasing communication both
within the Commission membership, as well as to the broader ILAE
membership through the Website project. With the increasing awareness
and interest in hereditary aspects of epilepsy in many different
societies, the Commission will seek to identify new initiatives
to promote international education and understanding of genes, as
well as the ethics and social issues of genetic research among professionals
and families affected by epilepsy. There is a continuing effort
to identify and implement specific projects previously represented
on the Commission, including malformations, pregnancy, teratogenetics,
and genetic counseling. This may involve a recommendation to the
Executive Committee in the coming year for creation of a new commission
or subcommissions. Increased contacts with WHO and IBE are planned,
along with participation in the International Congress on Human
Annual Report 2002 Table of Contents