Late diagnoses of Dravet syndrome: How many individuals are we missing?

Abstract We report new genetic diagnoses of Dravet syndrome in a group of adults with complex epilepsy of unknown cause, under follow‐up at a tertiary epilepsy center. Individuals with epilepsy and other features of unknown cause from our unit underwent whole‐genome sequencing through the 100 000 Ge...

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Autores principales:	Katri Silvennoinen, Clinda Puvirajasinghe, Kirsty Hudgell, Meneka K. Sidhu, Helena Martins Custodio, Genomics England Research Consortium, Wendy D. Jones, Simona Balestrini, Sanjay M. Sisodiya
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	epilepsy genetics seizures whole‐genome sequencing Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/3eb93497700946c19517fb07bc3808c4
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spelling	oai:doaj.org-article:3eb93497700946c19517fb07bc3808c42021-12-01T06:09:19ZLate diagnoses of Dravet syndrome: How many individuals are we missing?2470-923910.1002/epi4.12525https://doaj.org/article/3eb93497700946c19517fb07bc3808c42021-12-01T00:00:00Zhttps://doi.org/10.1002/epi4.12525https://doaj.org/toc/2470-9239Abstract We report new genetic diagnoses of Dravet syndrome in a group of adults with complex epilepsy of unknown cause, under follow‐up at a tertiary epilepsy center. Individuals with epilepsy and other features of unknown cause from our unit underwent whole‐genome sequencing through the 100 000 Genomes Project. Virtual gene panels were applied to frequency‐filtered variants based on phenotype summary. Of 1078 individuals recruited, 8 (0.74%) were identified to have a pathogenic or likely pathogenic variant in SCN1A. Variant types were as follows: nonsense (stopgain) in five (62.5%) and missense in three (37.5%). Detailed review of childhood history confirmed a phenotype compatible with Dravet syndrome. Median age at genetic diagnosis was 44.5 years (range 28‐52 years). Tonic‐clonic seizures were ongoing in all despite polytherapy including valproate. All had a history of fever sensitivity and myoclonic seizures, which were ongoing in two (25%) and three (37.5%) individuals, respectively. Salient features of Dravet syndrome may be less apparent in adulthood, making clinical diagnosis difficult. Regardless of age, benefits of a genetic diagnosis include access to syndrome‐specific treatment options, avoidance of harmful drugs, and monitoring for common complications.Katri SilvennoinenClinda PuvirajasingheKirsty HudgellMeneka K. SidhuHelena Martins CustodioGenomics England Research ConsortiumWendy D. JonesSimona BalestriniSanjay M. SisodiyaWileyarticleepilepsygeneticsseizureswhole‐genome sequencingNeurology. Diseases of the nervous systemRC346-429ENEpilepsia Open, Vol 6, Iss 4, Pp 770-776 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	epilepsy genetics seizures whole‐genome sequencing Neurology. Diseases of the nervous system RC346-429
spellingShingle	epilepsy genetics seizures whole‐genome sequencing Neurology. Diseases of the nervous system RC346-429 Katri Silvennoinen Clinda Puvirajasinghe Kirsty Hudgell Meneka K. Sidhu Helena Martins Custodio Genomics England Research Consortium Wendy D. Jones Simona Balestrini Sanjay M. Sisodiya Late diagnoses of Dravet syndrome: How many individuals are we missing?
description	Abstract We report new genetic diagnoses of Dravet syndrome in a group of adults with complex epilepsy of unknown cause, under follow‐up at a tertiary epilepsy center. Individuals with epilepsy and other features of unknown cause from our unit underwent whole‐genome sequencing through the 100 000 Genomes Project. Virtual gene panels were applied to frequency‐filtered variants based on phenotype summary. Of 1078 individuals recruited, 8 (0.74%) were identified to have a pathogenic or likely pathogenic variant in SCN1A. Variant types were as follows: nonsense (stopgain) in five (62.5%) and missense in three (37.5%). Detailed review of childhood history confirmed a phenotype compatible with Dravet syndrome. Median age at genetic diagnosis was 44.5 years (range 28‐52 years). Tonic‐clonic seizures were ongoing in all despite polytherapy including valproate. All had a history of fever sensitivity and myoclonic seizures, which were ongoing in two (25%) and three (37.5%) individuals, respectively. Salient features of Dravet syndrome may be less apparent in adulthood, making clinical diagnosis difficult. Regardless of age, benefits of a genetic diagnosis include access to syndrome‐specific treatment options, avoidance of harmful drugs, and monitoring for common complications.
format	article
author	Katri Silvennoinen Clinda Puvirajasinghe Kirsty Hudgell Meneka K. Sidhu Helena Martins Custodio Genomics England Research Consortium Wendy D. Jones Simona Balestrini Sanjay M. Sisodiya
author_facet	Katri Silvennoinen Clinda Puvirajasinghe Kirsty Hudgell Meneka K. Sidhu Helena Martins Custodio Genomics England Research Consortium Wendy D. Jones Simona Balestrini Sanjay M. Sisodiya
author_sort	Katri Silvennoinen
title	Late diagnoses of Dravet syndrome: How many individuals are we missing?
title_short	Late diagnoses of Dravet syndrome: How many individuals are we missing?
title_full	Late diagnoses of Dravet syndrome: How many individuals are we missing?
title_fullStr	Late diagnoses of Dravet syndrome: How many individuals are we missing?
title_full_unstemmed	Late diagnoses of Dravet syndrome: How many individuals are we missing?
title_sort	late diagnoses of dravet syndrome: how many individuals are we missing?
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/3eb93497700946c19517fb07bc3808c4
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Late diagnoses of Dravet syndrome: How many individuals are we missing?

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