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Chapter 5

Genetics of the epilepsies

SANJAY SISODIYA

UCL Institute of Neurology, University College London, National Hospital for Neurology
and Neurosurgery, Queen Square, London, and Epilepsy Society, Chalfont St Peter,
Buckinghamshire

Introduction

Genetics is a huge and growing area across human biology and medicine, providing
information about basic processes from birth to death, from development to degeneration,
and in some instances revealing enough about disease biology to lead to rational new
therapies or better use of existing treatments. There is much hope that the power of genetics
to provide insights into how diseases start and develop will lead to smarter therapies that in
turn will make care not only more effective, but also more cost-efficient. This is particularly
an issue for healthcare systems in developed economies where chronic conditions are
becoming key issues. One can only hope that genetics will provide benefits also for
developing regions, in the way that mobile telephony bypasses the need for more expensive
infrastructure. Whether these hopes will be realised remains to be seen and answers are likely
to be forthcoming in the next few years.

Genetics can empower all sides in the healthcare setting, from the person with the condition
to the physician delivering care. Much has already been written about the experience and
perspective of people with epilepsy, and there will be more to come, but this will form the
focus of the current chapter. Physicians are excellent at seeing patterns in their patients:
genetics can produce biological explanations for such patterns and for unusual deviations
from such patterns. Syndromes become explicable diseases, and clinicians will remain the
key element in the translation of genetic discovery to clinic for the benefit of people with
epilepsy. The pace of such discovery and the magnitude of the challenge ahead will come as
a surprise to most of us. It is therefore important that everyone involved in treating epilepsy
should have some grounding in genetics, and in epilepsy genetics. By providing information,
probably the most available from any single test, genetics will change our thinking about
epilepsy, at least as much as did EEG and MRI. People with epilepsy themselves, and their
families and carers, are already pushing ahead. Genetics offers real possibility for meaningful
collaboration not just between scientists and clinicians, but also between all parties, including
funders, providers and, most of all, those with the conditions.

We have long known that ‘epilepsy’ is not one condition. Progress in the genetics of the
epilepsies is providing a factual landscape for this established diversity of the epilepsies.
Today’s challenges are not to acquire genetic data, but to interpret the vastness of the data
emerging from genetic work in the epilepsies in the context of the even larger universe of
genetic data across the life sciences. In this context, this chapter will focus more on concepts
than on individual genes. Any printed list of genes linked with an epilepsy is soon dated.

Background

As is well known, a role for genetics has long been postulated in the epilepsies, derived from
observations in families. More broadly, the ‘neurological trait’ is a phenomenon talked about
by clinically-astute neurologists for many years (see, for example, Gowers 18811) – it is,