i-manager Publications

Epilepsy and Genetics: A Review

Sibiya Dinesh*, Jebi Sudan**, Nikita Ojha***, Ekta Menghani****, Hardik Pathak*****, Rajendra Kumar Sureka******

*-***** Department of Biotechnology, JECRC University, Jaipur, Rajasthan, India.

****** Department of Neurology, Mahatma Gandhi Medical College, Jaipur, Rajasthan, India.

Periodicity:January - April'2023
DOI : https://doi.org/10.26634/jls.2.1.19314

Abstract

The term "epilepsy" refers to a wide range of conditions, the majority of which are triggered by interactions between many genes and environmental variables. Genetic epilepsies caused by single-gene alterations or specific structural chromosomal anomalies such as micro-deletions are much infrequent. These rare genetic forms of epilepsy often exhibit distinct clinical features and can provide valuable insights into the underlying biological mechanisms involved in seizure generation. The advancements in epilepsy genetics over the last ten to twenty years have opened up new avenues for diagnosis and treatment. For instance, many types of genetic epilepsies are discussed to show the multiple paths that might lead from genes to seizures. It has become evident that different genetic alterations can disrupt neuronal excitability, synaptic function, ion channel activity, or other critical biological processes, ultimately leading to seizure activity. Furthermore, the identification of specific genetic variants associated with drug response or treatment resistance has provided valuable insights into personalized therapeutic strategies for individuals with epilepsy.

Keywords

Epilepsy, Genetics, Ion Channel Mutations, Non-Ion Channel Mutations, Genetic Tests, Practical Considerations.

How to Cite this Article?

Dinesh, S., Sudan, J., Ojha, N., Menghani, E., Pathak, H., and Sureka, R. K. (2023). Epilepsy and Genetics: A Review. i-manager’s Journal on Life Sciences, 2(1), 20-30. https://doi.org/10.26634/jls.2.1.19314

References

[1]. Al-Absi, A. R., Qvist, P., Glerup, S., Sanchez, C., & Nyengaard, J. R. (2021). Df (h15q13)/+ mouse model reveals loss of astrocytes and synaptic-related changes of the excitatory and inhibitory circuits in the medial prefrontal cortex. Cerebral Cortex, 31(3), 1609-1621.

[2]. Camfield, P., & Camfield, C. (2015). Febrile seizures and genetic epilepsy with febrile seizures plus (GEFS+). Epileptic Disorders, 17(2), 124-133.

[3]. De Jonghe, P. (2011). Molecular genetics of Dravet syndrome. Developmental Medicine & Child Neurology, 53(s2), 7-10.

[4]. Fukuyama, K., Fukuzawa, M., Shiroyama, T., & Okada, M. (2020). Pathogenesis and pathophysiology of autosomal dominant sleep related hypermotor epilepsy with S284L mutant α4 subunit of nicotinic ACh receptor. British Journal of Pharmacology, 177(9), 2143-2162.

[5]. Fusco, M. D., Becchetti, A., Patrignani, A., Annesi, G., Gambardella, A., Quattrone, A., ... & Casari, G. (2000). The nicotinic receptor β2 subunit is mutant in nocturnal frontal lobe epilepsy. Nature Genetics, 26(3), 275-276.

[6]. Gandolfi, D., Boiani, G. M., Bigiani, A., & Mapelli, J. (2021). Modeling neurotransmission: Computational tools to investigate neurological disorders. International Journal of Molecular Sciences, 22(9), 4565.

[7]. Goniotaki, D., Tamagnini, F., Biasetti, L., Rumpf, S. L., Fennell, K., Pollack, S. J., ... & Hanger, D. P. (2020). Synaptic dysfunction caused by truncated tau is associated with hyperpolarization-activated cyclic nucleotide-gated channelopathy. bioRxiv, (1-41).

[8]. Heron, S. E., Crossland, K. M., Andermann, E., Phillips, H. A., Hall, A. J., Bleasel, A., ... & Scheffer, I. E. (2002). Sodium-channel defects in benign familial neonatalinfantile seizures. The Lancet, 360(9336), 851-852.

[9]. Heron, S. E., Scheffer, I. E., Berkovic, S. F., Dibbens, L. M., & Mulley, J. C. (2007). Channelopathies in idiopathic epilepsy. Neurotherapeutics, 4(2), 295-304.

[10]. Higurashi, N., Broccoli, V., & Hirose, S. (2022). Genetics and gene therapy in Dravet syndrome. Epilepsy & Behavior, 131, 108043.

[11]. Jepps, T. A., Barrese, V., & Miceli, F. (2021). Kv7 Channels: Structure, physiology, and pharmacology. Frontiers in Physiology, 12, 679317.

[12]. Juvale, I. I. A., & Has, A. T. C. (2021). Possible interplay between the theories of pharmacoresistant epilepsy. European Journal of Neuroscience, 53(6), 1998-2026.

[13]. Kato, M., Yamagata, T., Kubota, M., Arai, H., Yamashita, S., Nakagawa, T., ... & Saitsu, H. (2013). Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia, 54(7), 1282-1287.

[14]. Kija, E., & Wilmshurst, J. M. (2020). Approach to a child with epilepsy. In M. A. Salih (Eds). Clinical Child Neurology. Springer, Cham (pp. 795-808).

[15]. Kojima, K., Shirai, K., Kobayashi, M., Miyauchi, A., Saitsu, H., Matsumoto, N., ... & Yamagata, T. (2018). A patient with early myoclonic encephalopathy (EME) with a de novo KCNQ2 mutation. Brain and Development, 40(1), 69-73.

[16]. Le Nguyen, T. H., Nguyen, Q. M. T., Le, K. V. T., Le, M. T. T., Le, A. N. T., Do, H. P., ... & Do, T. H. T. (2021). A novel KCNQ2 gene mutation in a patient with self-limitted nonfamilial neonatal epilepsy: a case report. VNUHCM Journal of Health Sciences, 2(1), 94-101.

[17]. Li, M., Niu, F., Zhu, X., Wu, X., Shen, N., Peng, X., & Liu, Y. (2015). PRRT2 mutant leads to dysfunction of glutamate signaling. International Journal of Molecular Sciences, 16(5), 9134-9151.

[18]. Lucchino, V., Scaramuzzino, L., Scalise, S., Grillone, K., Conte, M. L., Esposito, C., ... & Cuda, G. (2021). Generation of human induced pluripotent stem cell lines (UNIMGi003-A and UNIMGi004-A) from two Italian siblings affected by Unverricht-Lundborg disease. Stem Cell Research, 53, 102329.

[19]. Ma, S., Wang, X., Du, X., Su, M., Yao, X., & Shi, J. (2020). Novel compatibility of huanglianjiedu decoction in behavioral and psychological symptoms of dementia in alzheimer's disease1. (pp. 1-14). ResearchSquare.

[20]. Massimino, C. R., Portale, L., Sapuppo, A., Pizzo, F., Sciuto, L., Romano, C., ... & Falsaperla, R. (2021). PRRT2 related epilepsies: A gene review. Journal of Pediatric Neurology.

[21]. Miao, P., Feng, J., Guo, Y., Wang, J., Xu, X., Wang, Y., ... & Cheng, H. (2018). Genotype and phenotype analysis using an epilepsy associated gene panel in Chinese pediatric epilepsy patients. Clinical Genetics, 94(6), 512-520.

[22]. Munivelan, B. (2020). Identification of the mutated sites present in the transmembrane regions of SCN1A_HUMAN (Sodium Voltage-Gated Channel Alpha Subunit 1) using Insilico techniques. International Journal of Pharmacometrics and Integrated Biosciences, 5(1), 1-6.

[23]. Nicita, F., De Liso, P., Danti, F. R., Papetti, L., Ursitti, F., Castronovo, A., ... & Spalice, A. (2012). The genetics of monogenic idiopathic epilepsies and epileptic encephalopathies. Seizure, 21(1), 3-11.

[24]. Okada, M. (2022). Can rodent models elucidate the pathomechanisms of genetic epilepsy?. British Journal of Pharmacology, 179(8), 1620-1639.

[25]. Ottman, R., & Poduri, A. (2020). Gene tests in adults with epilepsy and intellectual disability. Nature Reviews Neurology, 16(10), 527-528.

[26]. Perrotta, G. (2020). Epilepsy: from pediatric to adulthood. Definition, classifications, neurobiological profiles and clinical treatments. Journal of Neurology, Neurological Science and Disorders, 6(1), 14-29.

[27]. Rosiles-Abonce, A., Rubio, C., Taddei, E., Rosiles, D., & Rubio-Osornio, M. (2021). Antiepileptogenic effect of retinoic acid. Current Neuropharmacology, 19(3), 383-391.

[28]. Saitsu, H., Kato, M., Koide, A., Goto, T., Fujita, T., Nishiyama, K., ... & Matsumoto, N. (2012). Whole exome sequencing identifies KCNQ2 mutations in Ohtahara syndrome. Annals of Neurology, 72(2), 298-300.

[29]. Sapuppo, A., Portale, L., Massimino, C. R., Presti, S., Tardino, L., Marino, S., ... & Praticò, A. D. (2021). GRIN2A and GRIN2B and their related phenotypes. Journal of Pediatric Neurology, 21(3), 212-223.

[30]. Scheffer, I. E., & Berkovic, S. F. (1997). Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes. Brain: A Journal of Neurology, 120(3), 479-490.

[31]. Singh, N. A., Westenskow, P., Charlier, C., Pappas, C., Leslie, J., Dillon, J., ... & Leppert, M. F. (2003). KCNQ2 and KCNQ3 potassium channel genes in benign familial neonatal convulsions: expansion of the functional and mutation spectrum. Brain, 126(12), 2726-2737.

[32]. Steel, D., Symonds, J. D., Zuberi, S. M., & Brunklaus, A. (2017). Dravet syndrome and its mimics: Beyond SCN 1A. Epilepsia, 58(11), 1807-1816.

[33]. Steinlein, O. K. (2008). Genetics and epilepsy. Dialogues in Clinical Neuroscience, 10(1), 29-38.

[34]. Stincic, T. L., Bosch, M. A., Hunker, A. C., Juarez, B., Connors, A. M., Zweifel, L. S., ... & Kelly, M. J. (2021). CRISPR knockdown of Kcnq3 attenuates the M-current and increases excitability of NPY/AgRP neurons to alter energy balance. Molecular Metabolism, 49, 101218.