Case Report: Novel Homozygous Likely Pathogenic SCN1A Variant With Autosomal Recessive Inheritance and Review of the Literature

Dominant pathogenic variations in the SCN1A gene are associated with several neuro developmental disorders with or without epilepsy, including Dravet syndrome (DS). Conversely, there are few published cases with homozygous or compound heterozygous variations in the SCN1A gene. Here, we describe two...

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Autores principales:	Ana Victoria Marco Hernández, Miguel Tomás Vila, Alfonso Caro Llopis, Sandra Monfort, Francisco Martinez
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	SCN1A Dravet syndrome GEFS+ homozygous autosomal recessive inheritance Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/3195abfa2c1744379b4f8e683fa56303
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spelling	oai:doaj.org-article:3195abfa2c1744379b4f8e683fa563032021-12-01T18:39:08ZCase Report: Novel Homozygous Likely Pathogenic SCN1A Variant With Autosomal Recessive Inheritance and Review of the Literature1664-229510.3389/fneur.2021.784892https://doaj.org/article/3195abfa2c1744379b4f8e683fa563032021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fneur.2021.784892/fullhttps://doaj.org/toc/1664-2295Dominant pathogenic variations in the SCN1A gene are associated with several neuro developmental disorders with or without epilepsy, including Dravet syndrome (DS). Conversely, there are few published cases with homozygous or compound heterozygous variations in the SCN1A gene. Here, we describe two siblings from a consanguineous pedigree with epilepsy phenotype compatible with genetic epilepsy with febrile seizures plus (GEFS+) associated with the homozygous likely pathogenic variant (NM_001165963.1): c.4513A > C (p.Lys1505Gln). Clinical and genetic data were compared to those of other 10 previously published patients with epilepsy and variants in compound heterozygosity or homozygosity in the SCN1A gene. Most patients (11/12) had missense variants. Patients in whom the variants were located at the cytoplasmic or the extracellular domains frequently presented a less severe phenotype than those in whom they are located at the pore-forming domains. Five of the patients (41.7%) meet clinical criteria for Dravet syndrome (DS), one of them associated acute encephalopathy. Other five patients (41.7%) had a phenotype of epilepsy with febrile seizures plus familial origin, while the two remaining (17%) presented focal epileptic seizures. SCN1A-related epilepsies present in most cases an autosomal dominant inheritance; however, there is growing evidence that some genetic variants only manifest clinical symptoms when they are present in both alleles, following an autosomal recessive inheritance.Ana Victoria Marco HernándezAna Victoria Marco HernándezMiguel Tomás VilaAlfonso Caro LlopisAlfonso Caro LlopisSandra MonfortFrancisco MartinezFrancisco MartinezFrontiers Media S.A.articleSCN1ADravet syndromeGEFS+homozygousautosomal recessive inheritanceNeurology. Diseases of the nervous systemRC346-429ENFrontiers in Neurology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	SCN1A Dravet syndrome GEFS+ homozygous autosomal recessive inheritance Neurology. Diseases of the nervous system RC346-429
spellingShingle	SCN1A Dravet syndrome GEFS+ homozygous autosomal recessive inheritance Neurology. Diseases of the nervous system RC346-429 Ana Victoria Marco Hernández Ana Victoria Marco Hernández Miguel Tomás Vila Alfonso Caro Llopis Alfonso Caro Llopis Sandra Monfort Francisco Martinez Francisco Martinez Case Report: Novel Homozygous Likely Pathogenic SCN1A Variant With Autosomal Recessive Inheritance and Review of the Literature
description	Dominant pathogenic variations in the SCN1A gene are associated with several neuro developmental disorders with or without epilepsy, including Dravet syndrome (DS). Conversely, there are few published cases with homozygous or compound heterozygous variations in the SCN1A gene. Here, we describe two siblings from a consanguineous pedigree with epilepsy phenotype compatible with genetic epilepsy with febrile seizures plus (GEFS+) associated with the homozygous likely pathogenic variant (NM_001165963.1): c.4513A > C (p.Lys1505Gln). Clinical and genetic data were compared to those of other 10 previously published patients with epilepsy and variants in compound heterozygosity or homozygosity in the SCN1A gene. Most patients (11/12) had missense variants. Patients in whom the variants were located at the cytoplasmic or the extracellular domains frequently presented a less severe phenotype than those in whom they are located at the pore-forming domains. Five of the patients (41.7%) meet clinical criteria for Dravet syndrome (DS), one of them associated acute encephalopathy. Other five patients (41.7%) had a phenotype of epilepsy with febrile seizures plus familial origin, while the two remaining (17%) presented focal epileptic seizures. SCN1A-related epilepsies present in most cases an autosomal dominant inheritance; however, there is growing evidence that some genetic variants only manifest clinical symptoms when they are present in both alleles, following an autosomal recessive inheritance.
format	article
author	Ana Victoria Marco Hernández Ana Victoria Marco Hernández Miguel Tomás Vila Alfonso Caro Llopis Alfonso Caro Llopis Sandra Monfort Francisco Martinez Francisco Martinez
author_facet	Ana Victoria Marco Hernández Ana Victoria Marco Hernández Miguel Tomás Vila Alfonso Caro Llopis Alfonso Caro Llopis Sandra Monfort Francisco Martinez Francisco Martinez
author_sort	Ana Victoria Marco Hernández
title	Case Report: Novel Homozygous Likely Pathogenic SCN1A Variant With Autosomal Recessive Inheritance and Review of the Literature
title_short	Case Report: Novel Homozygous Likely Pathogenic SCN1A Variant With Autosomal Recessive Inheritance and Review of the Literature
title_full	Case Report: Novel Homozygous Likely Pathogenic SCN1A Variant With Autosomal Recessive Inheritance and Review of the Literature
title_fullStr	Case Report: Novel Homozygous Likely Pathogenic SCN1A Variant With Autosomal Recessive Inheritance and Review of the Literature
title_full_unstemmed	Case Report: Novel Homozygous Likely Pathogenic SCN1A Variant With Autosomal Recessive Inheritance and Review of the Literature
title_sort	case report: novel homozygous likely pathogenic scn1a variant with autosomal recessive inheritance and review of the literature
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/3195abfa2c1744379b4f8e683fa56303
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Case Report: Novel Homozygous Likely Pathogenic SCN1A Variant With Autosomal Recessive Inheritance and Review of the Literature

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