Familial Mesial Temporal Lobe Epilepsy: Clinical Spectrum and Genetic Evidence for a Polygenic Architecture

• DOI: 10.1002/ana.26765
• Publication Date: 2023-08-22T00:29:51Z
• Authors: Rebekah V. Harris; Karen L. Oliver; Piero Perucca; Pasquale Striano; Angelo Labate; Antonella Riva; Bronwyn E. Grinton; Joshua Reid; Jessica Hutton; Marian Todaro; Terence J. O'Brien; Patrick Kwan; Lynette G. Sadleir; Saul A. Mullen; Emanuela Dazzo; Douglas E. Crompton; Ingrid E. Scheffer; Melanie Bahlo; Carlo Nobile; Antonio Gambardella; Samuel F. Berkovic
• Keywords: Hippocampal sclerosis; Interquartile range; Epilepsy syndromes; Seizure types

Objective Familial mesial temporal lobe epilepsy (FMTLE) is an important focal syndrome; its molecular genetic basis unknown. Clinical descriptions of FMTLE vary between a mild syndrome with prominent déjà vu to more severe phenotype febrile seizures and hippocampal sclerosis. We aimed refine the by analyzing large cohort patients asked whether common risk variants for and/or seizures, measured polygenic scores (PRS), are enriched in individuals FMTLE. Methods studied 134 families ≥ 2 first or second‐degree relatives epilepsy, clear ictal semiology required at least one individual. PRS were calculated 227 cases, 124 unaffected relatives, 16,077 population controls. Results The age onset ranged from 2.5 70 years (median = 18, interquartile range 13–28 years). most seizure symptom was (62% cases), followed epigastric rising sensation (34%), fear anxiety (22%). clinical spectrum included rare cases drug‐resistance had higher mean than controls (odds ratio 1.24, 95% confidence interval 1.06, 1.46, p 0.007); contrast, no enrichment observed. Interpretation generally drug‐responsive being commonest symptom. In contrast dominant monogenic syndromes, our data support Furthermore, suggest that sub‐genome‐wide significant genome‐wide association study single nucleotide polymorphisms ANN NEUROL 2023;94:825–835