The revolution in epilepsy genetics changes clinical practice

Ingrid Scheffer MBBS PhD FRACP

Professor Ingrid Scheffer’s work has resulted in major paradigm shifts in epilepsy syndromology and classification over many years. Her work has formed the essential basis for successful gene discovery such that her larger collaborative group has been the leaders in epilepsy gene identification for 18 years since they discovered the first gene associated with epilepsy. This body of work has resulted in insights into the biology of seizures.

Professor Scheffer is Chair of Paediatric Neurology Research at The University of Melbourne and Senior Principal Research Fellow at the Florey Institute of Neuroscience and Mental Health.

Ingrid and her colleagues have described a range of novel epilepsy syndromes beginning in infancy, childhood and adult life. Her work has meant that children and adults with sodium channel disorders such as Dravet syndrome and related epilepsies are diagnosed earlier and treated appropriately which improves their long term outcomes. Her recent work on a fascinating disorder occurring exclusively in females, Epilepsy limited to Females with Mental Retardation, is changing the way family histories are interpreted and will benefit affected women and transmitting men by improving genetic counseling. She has considerably expanded our understanding of the spectrum of epilepsies associated with glucose transporter deficiency; this body of work carries major treatment implications as this disorder responds to the ketogenic diet. Her work is important as it has changed our concepts of the underlying neurobiology of genetic epilepsies.

In 2012, Professor Scheffer was awarded the L'Oréal-UNESCO Laureate for Women in Science for the Asia-Pacific Region, and travelled to Paris to receive the award. In the past Prof Scheffer has received the 2007 American Epilepsy Society Research Recognition Award and the 2009 Eric Susman Prize from the Royal Australasian College Of Physicians. She has served the International League Against Epilepsy in many capacities and held the Chair of the ILAE Commission for Classification and Terminology from 2009 until 2013. The ILAE presented her with the Ambassador for Epilepsy award in 2013 and in the same year, she received the Emil Becker Award for an outstanding contribution to child neurology, the Australian Neuroscience Medallion and the prestigious national prize, the GlaxoSmithKline Award for Research Excellence.

The L’Oréal-UNESCO Awards, which were first created in 1998, recognise five outstanding women researchers each year who have contributed to scientific progress. There is one Laureate from each of the five major regions of the world: Africa and Arab States, Asia (including Oceania and Pacific), Europe, Latin America and North America. It is intended that these exceptional women scientists serve as role models for the next generation, encouraging young women around the world to follow in their footsteps. Prof Scheffer’s award is the first for an epilepsy researcher, and this prize provides great visibility to her work throughout the epilepsy research community. It is also an example of the great strides that can be made when a talented group of researchers combine their complementary skills.

Professor Scheffer is Director of Paediatrics at Austin Health.

Source: http://www.ingridscheffer.com/

Talk:

The revolution in epilepsy genetics changes clinical practice

With the advent of next generation sequencing, there has been a virtual explosion in the number of known epilepsy genes which has been especially prolific in the last two years. The major areas of impact are the focal epilepsies, a group previously considered predominantly acquired disorders apart from rare large families with autosomal dominant disorders.

With the new gene discoveries, there is a paradigm shift with regard to evaluation of children and adolescents with focal epilepsies, and includes both lesional and non-lesional cases. These findings have implications for aetiology but also for management as particular genes may suggest that the patient should be scrutinized for a focal cortical dysplasia.

New focal epilepsy genes are shedding light on novel mechanisms with the mammalian target of rapamycin pathway becoming a critical pathway in focal epilepsy apart from tuberous sclerosis. The epileptic encephalopathies are proving to be genetically highly heterogeneous with many patients having de novo dominant mutations.

As new genes are discovered, the phenotypes of specific genetic encephalopathies are emerging, and may have distinctive features that aid diagnosis. Cohorts of patients with a specific diseases will rapidly grow and this, in turn, will inform treatment choices and long term prognosis.