SCN1A Channels a Wide Range of Epileptic Phenotypes: Report of Novel and Known Variants with Variable Presentations

Veltra, Danai; Theodorou, Virginia; Katsalouli, Marina; Vorgia, Pelagia; Niotakis, Georgios; Tsaprouni, Triantafyllia; Pons, Roser; Kosma, Konstantina; Kampouraki, Afroditi; Tsoutsou, Irene; Makrythanasis, Periklis; Kekou, Kyriaki; Traeger-Synodinos, Joanne; Sofocleous, Christalena

doi:10.3390/ijms25115644

Open AccessArticle

SCN1A Channels a Wide Range of Epileptic Phenotypes: Report of Novel and Known Variants with Variable Presentations

by

Danai Veltra

^1,2

,

Virginia Theodorou

³,

Marina Katsalouli

³,

Pelagia Vorgia

⁴,

Georgios Niotakis

⁵,

Triantafyllia Tsaprouni

⁶,

Roser Pons

⁷,

Konstantina Kosma

¹,

Afroditi Kampouraki

¹

,

Irene Tsoutsou

¹,

Periklis Makrythanasis

^1,8,9,

Kyriaki Kekou

¹

,

Joanne Traeger-Synodinos

¹

and

Christalena Sofocleous

^1,*

¹

Laboratory of Medical Genetics, Medical School, National and Kapodistrian University of Athens, St. Sophia’s Children’s Hospital, 11527 Athens, Greece

²

Research University Institute for the Study and Prevention of Genetic and Malignant Disease of Childhood, National and Kapodistrian University of Athens, St. Sophia’s Children’s Hospital, 11527 Athens, Greece

³

Pediatric Neurology Department, St. Sophia’s Children’s Hospital, 11527 Athens, Greece

⁴

Agrifood and Life Sciences Institute, Hellenic Mediterranean University, 71410 Heraklion, Greece

⁵

Pediatric Neurology Department, Venizelion Hospital, 71409 Heraklion, Greece

⁶

Pediatric Neurology Department, Tzaneio Hospital, 18536 Piraeus, Greece

⁷

First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, St. Sophia’s Children’s Hospital, 11527 Athens, Greece

⁸

Department of Genetic Medicine and Development, Medical School, University of Geneva, 1211 Geneva, Switzerland

⁹

Biomedical Research Foundation of the Academy of Athens, 11527 Athens, Greece

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2024, 25(11), 5644; https://doi.org/10.3390/ijms25115644

Submission received: 3 April 2024 / Revised: 15 May 2024 / Accepted: 18 May 2024 / Published: 22 May 2024

(This article belongs to the Special Issue Molecular Diagnostics and Therapeutics of Epileptic Neurodevelopment)

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Abstract

SCN1A, the gene encoding for the Nav1.1 channel, exhibits dominant interneuron-specific expression, whereby variants disrupting the channel’s function affect the initiation and propagation of action potentials and neuronal excitability causing various types of epilepsy. Dravet syndrome (DS), the first described clinical presentation of SCN1A channelopathy, is characterized by severe myoclonic epilepsy in infancy (SMEI). Variants’ characteristics and other genetic or epigenetic factors lead to extreme clinical heterogeneity, ranging from non-epileptic conditions to developmental and epileptic encephalopathy (DEE). This current study reports on findings from 343 patients referred by physicians in hospitals and tertiary care centers in Greece between 2017 and 2023. Positive family history for specific neurologic disorders was disclosed in 89 cases and the one common clinical feature was the onset of seizures, at a mean age of 17 months (range from birth to 15 years old). Most patients were specifically referred for SCN1A investigation (Sanger Sequencing and MLPA) and only five for next generation sequencing. Twenty-six SCN1A variants were detected, including nine novel causative variants (c.4567A>Τ, c.5564C>A, c.2176+2T>C, c.3646G>C, c.4331C>A, c.1130_1131delGAinsAC, c.1574_1580delCTGAGGA, c.4620A>G and c.5462A>C), and are herein presented, along with subsequent genotype–phenotype associations. The identification of novel variants complements SCN1A databases extending our expertise on genetic counseling and patient and family management including gene-based personalized interventions.

Keywords: epilepsy; genotype; phenotypic spectrum; sodium channelopathy; Dravet syndrome

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MDPI and ACS Style

Veltra, D.; Theodorou, V.; Katsalouli, M.; Vorgia, P.; Niotakis, G.; Tsaprouni, T.; Pons, R.; Kosma, K.; Kampouraki, A.; Tsoutsou, I.; et al. SCN1A Channels a Wide Range of Epileptic Phenotypes: Report of Novel and Known Variants with Variable Presentations. Int. J. Mol. Sci. 2024, 25, 5644. https://doi.org/10.3390/ijms25115644

AMA Style

Veltra D, Theodorou V, Katsalouli M, Vorgia P, Niotakis G, Tsaprouni T, Pons R, Kosma K, Kampouraki A, Tsoutsou I, et al. SCN1A Channels a Wide Range of Epileptic Phenotypes: Report of Novel and Known Variants with Variable Presentations. International Journal of Molecular Sciences. 2024; 25(11):5644. https://doi.org/10.3390/ijms25115644

Chicago/Turabian Style

Veltra, Danai, Virginia Theodorou, Marina Katsalouli, Pelagia Vorgia, Georgios Niotakis, Triantafyllia Tsaprouni, Roser Pons, Konstantina Kosma, Afroditi Kampouraki, Irene Tsoutsou, and et al. 2024. "SCN1A Channels a Wide Range of Epileptic Phenotypes: Report of Novel and Known Variants with Variable Presentations" International Journal of Molecular Sciences 25, no. 11: 5644. https://doi.org/10.3390/ijms25115644

APA Style

Veltra, D., Theodorou, V., Katsalouli, M., Vorgia, P., Niotakis, G., Tsaprouni, T., Pons, R., Kosma, K., Kampouraki, A., Tsoutsou, I., Makrythanasis, P., Kekou, K., Traeger-Synodinos, J., & Sofocleous, C. (2024). SCN1A Channels a Wide Range of Epileptic Phenotypes: Report of Novel and Known Variants with Variable Presentations. International Journal of Molecular Sciences, 25(11), 5644. https://doi.org/10.3390/ijms25115644

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SCN1A Channels a Wide Range of Epileptic Phenotypes: Report of Novel and Known Variants with Variable Presentations

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