At what point in the course of chronic epilepsy is finding the etiology no longer worthwhile? Is it fair to assume there comes a point where knowing the cause is no longer beneficial to the patient? If that time exists, is it the medical equivalent of waving the white flag?
Understanding the genetic basis of epilepsy has changed the way treatment is delivered, particularly for patients with epileptic encephalopathies. For the majority of people with seizures, regardless of severity, understanding the etiology of their epilepsy brings an end to the diagnostic odyssey that for many has included years of testing and uncertainties about the future. Multigene panels and whole-exome sequencing have primarily been used in pediatric populations where the downstream value of accurate diagnosis is likely highest and programs providing free testing make the early identification of syndromes where the course of treatment may be altered easier. Genetic testing has particularly high yield for children with early-life epilepsy and epileptic encephalopathies where the diagnostic hit rate can exceed 25%, approaching the yield of imaging and surpassing that of metabolic testing. Unfortunately, for adults with chronic epilepsy of childhood onset, the bus has often left the station, and they are not afforded the same advances in gene testing. The question is whether that matters and the answer is we don’t really know.
The limited use of genetic testing in adults is likely multifactorial. Essentially, all of the genetic epileptic encephalopathies have onset in childhood where the majority of research interest in diagnosis and treatment of these disorders exists. Unfortunately, this fails to acknowledge the undiagnosed adult patients who could benefit if afforded the same advances in treatment. For many of these conditions, early mortality has been the rule, thus many may consider testing low yield in older individuals. However, most of these conditions represent a phenotypic spectrum that is only now becoming more obvious as increasing numbers of individuals are diagnosed, thus we truly have no handle on the number of individuals with more favorable courses. Many adults with epilepsy and intellectual disabilities may no longer have strong advocates in the search for a diagnosis as they would have had as children, thus no voice to push for genetic testing. Finally, many question whether the outcome is altered in an adult who has suffered so many years with these conditions. This is a question that will remain unanswered if we don’t identify adults living with these disorders now. Ultimately, the goal of care should likely be to decrease the burden of disease for every individual with epilepsy and having a precise diagnosis to provide the most effective care would be the obvious path to consider.