It’s great having so many genetic tests for epilepsy, but what good do they do? Does finding the genetic cause change how we treat the person with epilepsy? Which people with epilepsy should we be testing? And what about antibody testing? Should we be doing this when we make a new diagnosis of epilepsy? The Genetic and Autoimmune Childhood Epilepsy (GACE) study has helped answer these questions.
The purpose of the GACE study was to understand how early genetic testing and antibody testing can improve the diagnosis and treatment of epilepsies. We focussed on children with epilepsy under the age of three.
Over the last 20 years, there has been a huge amount of progress in our understanding of genetic and autoimmune diseases, including epilepsy. Over 400 different genetic causes of epilepsy are now known. 20 different antineuronal antibodies (immune proteins made by the body which target brain tissue) are also now known to be associated with epilepsy. However, access to genetic and antibody testing has varied between regions, and the use of these tests in epilepsy clinics has been patchy. Therefore, our understanding of the role of genes and antibodies in epilepsy overall is quite weak. We wanted to broaden and deepen our understanding of genetic and autoimmune epilepsies by offering these tests to every child presenting with epilepsy who didn’t have a pre-existing diagnosis that explained their seizures. We wanted to send these tests as early as possible after onset of seizures. This would help us to see how early knowledge of genetic and autoimmune causes affects clinical management and treatment decisions.
We set up a Scottish national cohort of early childhood epilepsy and aimed to recruit every child with epilepsy before their 3rd birthday over a three-year period, from May 2014 to May 2017. We also included children with a first episode of status epilepticus (a seizure lasting more than 30 minutes), and children with certain types of complex febrile seizure, since we expected some of these to have genetic and autoimmune findings as well. Fortunately for us the paediatric centres in Scotland which diagnose and look after children with seizures work very closely together. They are connected by a managed clinical network called the Scottish Paediatric Epilepsy Network (SPEN), through which the study was organised and promoted. Families were given complete information about the study and were asked to sign consent for their child’s anonymised medical information to be collected. A single blood sample was taken and sent for genetic testing (in Glasgow) and antibody testing (in Oxford). We followed up with the children to see how their epilepsy changed. Parents kindly completed questionnaires so that we could evaluate each child’s developmental progress.
Over the three-years we recruited 343 children with seizures. We were surprised by just how many of these children’s epilepsy had a genetic cause (24%). Even children with self-limited epilepsies (seizures that were easily controlled) had genetic causes. We found genetic testing to be useful for clinicians and families, as getting a genetic diagnosis had potential to guide treatment choice in 80% of cases. Knowledge of genetic cause also helped epilepsy specialists and geneticists to give families accurate advice on prognosis (what the future was likely to hold) and recurrence risk for future offspring in the family. Our findings were published .
In contrast, antibody testing did not turn out to be useful in this age group. Although 6% of the cohort were found to have antibodies, these did not relate to the type of epilepsy and did not guide treatment. Other data suggests that about 6% of the healthy population will have the same antibodies. These findings were published here.
The children in this study remain under follow-up as we continue to develop this project. Our team of academic psychologists have analysed the data from the parent questionnaires and will publish this soon. We have expanded the cohort to now include children with structural causes. We have published two-year follow-up data from this larger cohort here.
To summarise, the key findings from the GACE study are:
Keep an eye out for future publications and blogs from us. This is a project that keeps on giving!
-Dr Joseph Symonds
