Etiology‐specific spectrum of epilepsy syndromes (ESSES): Widening the concept of etiology‐specific epilepsies—Report from the
ILAE
2021–2025 Terminology Commission
Ingrid E. Scheffer, Stéphane Auvin, Francesca Bisulli, Scott Demarest, Elena Gardella, Angelina Kakooza Mwesige, Rima Nabbout, Alshimaa S. Othman, Kollencheri Puthenveettil Vinayan, Robyn Whitney, Elaine Wirrell, Hideo Yamanouchi, Ji Yeoun Yoo, Sameer M. Zuberi, J. Helen Cross, Nicola Specchio Abstract
A new type of epilepsy syndrome, an etiology‐specific epilepsy syndrome, was defined in 2022 in recognition of major advances in identifying the many genetic and acquired etiologies underlying the epilepsies. An etiology‐specific epilepsy syndrome refers to where a known etiology is associated with a distinctive epilepsy presentation, including age at seizure onset, seizure types, and other morbidities, such as learning difficulties or intellectual disability, psychiatric features, gut and musculoskeletal problems. However, as we understand more about a specific etiology, such as a gene, it is clear that many etiologies are associated not just with one epilepsy syndrome, but with a range of epilepsy syndromes. Different epilepsy syndromes due to an abnormality in the same gene may reflect different types of dysfunction caused by the specific pathogenic genetic variant. Here, we expand the concept because—knowing the genetic etiology is not enough to ensure optimal clinical care—it requires a more nuanced approach to ensure the patient is managed appropriately. We define the concept of an etiology‐specific spectrum of epilepsy syndromes (ESSES), which incorporates understanding the range of epilepsy syndromes that may be associated with a specific etiology. In some cases, a genetic etiology may be associated with a functional spectrum, such as pathogenic variants in an ion channel subunit that cause loss‐of‐function, gain‐of‐function, or mixed functional effects, each associated with specific epilepsy syndromes that may require different treatment approaches. With other genes, the functional effect may not yet be known, but their spectrum of epilepsy syndromes may be well established through genotype–phenotype studies. The concept of ESSES has the flexibility to grow in its scope with new insights gained from understanding the breadth of epilepsy syndromes associated with a specific etiology and the associated functional impact.