Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Jan 19, 2022; 12(1): 98-107
Published online Jan 19, 2022. doi: 10.5498/wjp.v12.i1.98
Molecular typing of familial temporal lobe epilepsy
Chao Liu, Xiao-Zhi Qiao, Zi-Han Wei, Mi Cao, Zhen-Yu Wu, Yan-Chun Deng
Chao Liu, Xiao-Zhi Qiao, Zi-Han Wei, Mi Cao, Yan-Chun Deng, Department of Neurology, The First Affiliated Hospital of Air Force Medical University, Xi'an 710032, Shaanxi Province, China
Zhen-Yu Wu, Department of Anatomy, Histology and Embryology and K.K. Leung Brain Research Centre, School of Basic Medicine, Air Force Medical University, Xi'an 710032, Shaanxi Province, China
Author contributions: Liu C and Qiao XZ drafted the manuscript; Wei ZH, Cao M and Wu ZY helped with information retrieval; Deng YC conceived this review and provided essential revisions; all authors reviewed the paper.
Supported by the National Key R&D Program of China, Precision Medicine Program -Cohort Study on Nervous System Diseases, No. 2017YFC0907702.
Conflict-of-interest statement: The authors declare that they have no conflicts of interest.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Yan-Chun Deng, MD, PhD, Chief Doctor, Professor, Department of Neurology, The First Affiliated Hospital of Air Force Medical University, No. 127 Changle West Road, Xi'an 710032, Shaanxi Province, China.
Received: February 28, 2021
Peer-review started: February 28, 2021
First decision: September 5, 2021
Revised: September 25, 2021
Accepted: December 2, 2021
Article in press: December 2, 2021
Published online: January 19, 2022

The pathogenesis of temporal lobe epilepsy (TLE) was originally considered to be acquired. However, some reports showed that TLE was clustered in some families, indicating a genetic etiology. With the popularity of genetic testing technology, eleven different types of familial TLE (FTLE), including ETL1-ETL11, have been reported, of which ETL9-ETL11 had not yet been included in the OMIM database. These types of FTLE were caused by different genes/Loci and had distinct characteristics. ETL1, ETL7 and ETL10 were characterized by auditory, visual and aphasia seizures, leading to the diagnosis of familial lateral TLE. ETL2, ETL3 and ETL6 showed prominent autonomic symptom and automatism with or without hippocampal abnormalities, indicating a mesial temporal origin. Febrile seizures were common in FTLEs such as ETL2, ETL5, ETL6 and ETL11. ETL4 was diagnosed as occipitotemporal lobe epilepsy with a high incidence of migraine and visual aura. Considering the diversity and complexity of the symptoms of TLE, neurologists enquiring about the family history of epilepsy should ask whether the relatives of the proband had experienced unnoticeable seizures and whether there is a family history of other neurological diseases carefully. Most FTLE patients had a good prognosis with or without anti-seizure medication treatment, with the exception of patients with heterozygous mutations of the CPA6 gene. The pathogenic mechanism was diverse among these genes and spans disturbances of neuron development, differentiation and synaptic signaling. In this article, we describe the research progress on eleven different types of FTLE. The precise molecular typing of FTLE would facilitate the diagnosis and treatment of FTLE and genetic counseling for this disorder.

Keywords: Temporal lobe epilepsy, Gene mutation, Gene locus, Phenotypes, Prognosis

Core Tip: Eleven types of familial temporal lobe epilepsy (FTLE) caused by single gene mutations or specific gene loci had been identified to date. The phenotype of FTLE was heterogenous and includes typical temporal lobe seizures and specific symptoms. We herein describe the etiology, inheritance, phenotype and prognosis of each type of FTLE and summarize their similarities and differences.