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Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population

Sudden death is a rare event in the pediatric population but with a social shock due to its presentation as the first symptom in previously healthy children. Comprehensive autopsy in pediatric cases identify an inconclusive cause in 40–50% of cases. In such cases, a diagnosis of sudden arrhythmic de...

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Autores principales: Martínez-Barrios, Estefanía, Cesar, Sergi, Cruzalegui, José, Hernandez, Clara, Arbelo, Elena, Fiol, Victoria, Brugada, Josep, Brugada, Ramon, Campuzano, Oscar, Sarquella-Brugada, Georgia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773373/
https://www.ncbi.nlm.nih.gov/pubmed/35052786
http://dx.doi.org/10.3390/biomedicines10010106
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author Martínez-Barrios, Estefanía
Cesar, Sergi
Cruzalegui, José
Hernandez, Clara
Arbelo, Elena
Fiol, Victoria
Brugada, Josep
Brugada, Ramon
Campuzano, Oscar
Sarquella-Brugada, Georgia
author_facet Martínez-Barrios, Estefanía
Cesar, Sergi
Cruzalegui, José
Hernandez, Clara
Arbelo, Elena
Fiol, Victoria
Brugada, Josep
Brugada, Ramon
Campuzano, Oscar
Sarquella-Brugada, Georgia
author_sort Martínez-Barrios, Estefanía
collection PubMed
description Sudden death is a rare event in the pediatric population but with a social shock due to its presentation as the first symptom in previously healthy children. Comprehensive autopsy in pediatric cases identify an inconclusive cause in 40–50% of cases. In such cases, a diagnosis of sudden arrhythmic death syndrome is suggested as the main potential cause of death. Molecular autopsy identifies nearly 30% of cases under 16 years of age carrying a pathogenic/potentially pathogenic alteration in genes associated with any inherited arrhythmogenic disease. In the last few years, despite the increasing rate of post-mortem genetic diagnosis, many families still remain without a conclusive genetic cause of the unexpected death. Current challenges in genetic diagnosis are the establishment of a correct genotype–phenotype association between genes and inherited arrhythmogenic disease, as well as the classification of variants of uncertain significance. In this review, we provide an update on the state of the art in the genetic diagnosis of inherited arrhythmogenic disease in the pediatric population. We focus on emerging publications on gene curation for genotype–phenotype associations, cases of genetic overlap and advances in the classification of variants of uncertain significance. Our goal is to facilitate the translation of genetic diagnosis to the clinical area, helping risk stratification, treatment and the genetic counselling of families.
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spelling pubmed-87733732022-01-21 Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population Martínez-Barrios, Estefanía Cesar, Sergi Cruzalegui, José Hernandez, Clara Arbelo, Elena Fiol, Victoria Brugada, Josep Brugada, Ramon Campuzano, Oscar Sarquella-Brugada, Georgia Biomedicines Review Sudden death is a rare event in the pediatric population but with a social shock due to its presentation as the first symptom in previously healthy children. Comprehensive autopsy in pediatric cases identify an inconclusive cause in 40–50% of cases. In such cases, a diagnosis of sudden arrhythmic death syndrome is suggested as the main potential cause of death. Molecular autopsy identifies nearly 30% of cases under 16 years of age carrying a pathogenic/potentially pathogenic alteration in genes associated with any inherited arrhythmogenic disease. In the last few years, despite the increasing rate of post-mortem genetic diagnosis, many families still remain without a conclusive genetic cause of the unexpected death. Current challenges in genetic diagnosis are the establishment of a correct genotype–phenotype association between genes and inherited arrhythmogenic disease, as well as the classification of variants of uncertain significance. In this review, we provide an update on the state of the art in the genetic diagnosis of inherited arrhythmogenic disease in the pediatric population. We focus on emerging publications on gene curation for genotype–phenotype associations, cases of genetic overlap and advances in the classification of variants of uncertain significance. Our goal is to facilitate the translation of genetic diagnosis to the clinical area, helping risk stratification, treatment and the genetic counselling of families. MDPI 2022-01-05 /pmc/articles/PMC8773373/ /pubmed/35052786 http://dx.doi.org/10.3390/biomedicines10010106 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Martínez-Barrios, Estefanía
Cesar, Sergi
Cruzalegui, José
Hernandez, Clara
Arbelo, Elena
Fiol, Victoria
Brugada, Josep
Brugada, Ramon
Campuzano, Oscar
Sarquella-Brugada, Georgia
Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population
title Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population
title_full Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population
title_fullStr Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population
title_full_unstemmed Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population
title_short Clinical Genetics of Inherited Arrhythmogenic Disease in the Pediatric Population
title_sort clinical genetics of inherited arrhythmogenic disease in the pediatric population
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8773373/
https://www.ncbi.nlm.nih.gov/pubmed/35052786
http://dx.doi.org/10.3390/biomedicines10010106
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