About research
- Genetics and epilepsy workshop 2006
Inheriting epilepsy
It's been known for a long time that epilepsy
can be inherited. Only a small number of syndromes
(amounting to perhaps 1% of all epilepsies)
are caused by the presence of a single "epilepsy
gene", inherited from the patient's father
or mother. These are called "monogenic"
epilepsies.
It now appears that many epilepsies are
caused by combinations of genes, which all
have separate subtle effects, all tending
to increase a person's susceptibility to
seizures. These types of epilepsy are called
"polygenic". Scientists are only
just beginning to identify these genes for
some epilepsies - for example the groups
of genes that cause disorders of the ion
channels in neurones (important for signal
transmission between brain cells). Many
of the epilepsies currently labelled as
"cryptogenic" or "idiopathic",
which account for up to 60% of all cases,
are thought to have some genetic basis.
Genes and anti-epileptic drugs
Our genes also affect the way our bodies
respond to medicines we take. A particular
mutation of the gene called ABCB1 3435,
associated with transporting drug molecules
into and out of cells, has been found to
be associated with having drug-resistant
epilepsy. The damaging effects of some anti-epileptic
drugs on a growing baby when taken by the
mother during pregnancy are suspected to
depend partly on an interaction between
the drug and the mother's genetic profile.
So genes can effect the efficacy of a drug
and also its side effects.
The promise of this branch of medicine,
called pharmacogenomics, is the development
of tailor-made treatment. One day, it is
hoped, a gene test will allow a doctor to
prescribe a drug for a person designed for
precisely their type of epilepsy. The same
test may allow a doctor to work out whether
a drug is likely to cause a harmful side
effect in a patient, so they can avoid prescribing
that drug. But with the very wide variation
in genetic bases of epilepsy, this may mean
thousands of types of drugs, and expensive
and complicated gene testing. It's not clear
whether this will ever be financially viable.
The workshop
The field of genetics in medicine has advanced
very quickly in recent years. The Foundation
therefore decided to dedicate a workshop
to assessing the current state of our knowledge
of genetics in epilepsy, and what the next
developments might be.
The Foundation's workshops provide an arena
for a full, expert and in-depth look at
an area of research which has advanced quickly
in recent years. Discussion includes both
clinical and scientific aspects of the topic.
The workshop was held in March 2006 at St
Catherine's College, Oxford, and was
chaired by Dr Sanjay Sisodiya of the Institute
of Neurology, and Dr Helen Cross of the
Institute of Child Health, who is also Chairman
of the Foundation.
John Harris from the Institute of Medicine,
Law and Bioethics in Manchester spoke about
the ethics of genetic testing for disease,
and the need to keep strict controls on
who has access to the data. José
Serratosa from Madrid, Spain, spoke about
the extent to which grouping epilepsy cases
by seizure type and age of onset should
be replaced with grouping them by genetic
background.
Renzo Guerrini from Pisa, Italy, described
the types of epilepsy caused by single genes
and the progress being made towards identifying
the combinations of genes behind multi-gene
epilepsies. Several presentations focused
on the strategies needed to identify susceptibility
genes for these types of epilepsy, and there
was general agreement that large studies
are needed, requiring collaboration between
centres and accurate and consistent classification
of clinical data. There were several technical
talks about laboratory techniques and statistical
methods used to conduct genetic studies
and analyse the data. Other speakers covered
specific diseases of the brain which can
cause epilepsy, including tuberous sclerosis
and focal cortical dysplasia, and whether
these have a genetic basis.
The workshop confirmed that we have come
a long way in a short time, but current
research has probably raised more questions
than it has answered. A fascinating comparison
was made by a talk from Paul Harrison of
the University of Oxford, who gave an overview
of the search for schizophrenia genes. While
it appears clear that schizophrenia is in
part determined by genetics, no genes or
gene mutations have been positively identified
as causative. Compared to this discipline
epileptologists are doing well: this was
encouraging! However while a number of the
genes causing the rare monogenic epilepsies
have been found, a lot of work remains to
be done to identify the genes responsible
for polygenic epilepsies, which are much
more common.
The proceedings of the workshop have been
accepted for publication in Epileptic
Disorders later in 2007.
