Familial Arrhythmogenic Cardiomyopathy: Clinical Determinants of Phenotype Discordance and the Impact of Endurance Sports
Arrhythmogenic cardiomyopathy (ACM) is primarily a familial disease with autosomal dominant inheritance. Incomplete penetrance and variable expression are common, resulting in diverse clinical manifestations. Although recent studies on genotype–phenotype relationships have improved our understanding...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Journal of Clinical Medicine |
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| Online Access: | https://www.mdpi.com/2077-0383/9/11/3781 |
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| author | Sarah Costa Alessio Gasperetti Argelia Medeiros-Domingo Deniz Akdis Corinna Brunckhorst Ardan M. Saguner Firat Duru |
| author_facet | Sarah Costa Alessio Gasperetti Argelia Medeiros-Domingo Deniz Akdis Corinna Brunckhorst Ardan M. Saguner Firat Duru |
| author_sort | Sarah Costa |
| collection | DOAJ |
| description | Arrhythmogenic cardiomyopathy (ACM) is primarily a familial disease with autosomal dominant inheritance. Incomplete penetrance and variable expression are common, resulting in diverse clinical manifestations. Although recent studies on genotype–phenotype relationships have improved our understanding of the molecular mechanisms leading to the expression of the full-blown disease, the underlying genetic substrate and the clinical course of asymptomatic or oligo-symptomatic mutation carriers are still poorly understood. We aimed to analyze different phenotypic expression profiles of ACM in the context of the same familial genetic mutation by studying nine adult cases from four different families with four different familial variants (two plakophilin-2 and two desmoglein-2) from the Swiss Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Registry. The affected individuals with the same genetic variants presented with highly variable phenotypes ranging from no disease or a classical, right-sided disease, to ACM with biventricular presentation. Moreover, some patients developed early-onset, electrically unstable disease whereas others with the same genetic variants presented with late-onset electrically stable disease. Despite differences in age, gender, underlying genotype, and other clinical characteristics, physical exercise has been observed as the common denominator in provoking an arrhythmic phenotype in these families. |
| first_indexed | 2024-03-10T14:37:59Z |
| format | Article |
| id | doaj.art-79fd02010f02460ca8c6c9818b1516a6 |
| institution | Directory Open Access Journal |
| issn | 2077-0383 |
| language | English |
| last_indexed | 2024-03-10T14:37:59Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Clinical Medicine |
| spelling | doaj.art-79fd02010f02460ca8c6c9818b1516a62023-11-20T22:01:03ZengMDPI AGJournal of Clinical Medicine2077-03832020-11-01911378110.3390/jcm9113781Familial Arrhythmogenic Cardiomyopathy: Clinical Determinants of Phenotype Discordance and the Impact of Endurance SportsSarah Costa0Alessio Gasperetti1Argelia Medeiros-Domingo2Deniz Akdis3Corinna Brunckhorst4Ardan M. Saguner5Firat Duru6University Heart Center Zurich, Division of Cardiology, 8091 Zurich, SwitzerlandUniversity Heart Center Zurich, Division of Cardiology, 8091 Zurich, SwitzerlandUniversity Heart Center Zurich, Division of Cardiology, 8091 Zurich, SwitzerlandUniversity Heart Center Zurich, Division of Cardiology, 8091 Zurich, SwitzerlandUniversity Heart Center Zurich, Division of Cardiology, 8091 Zurich, SwitzerlandUniversity Heart Center Zurich, Division of Cardiology, 8091 Zurich, SwitzerlandUniversity Heart Center Zurich, Division of Cardiology, 8091 Zurich, SwitzerlandArrhythmogenic cardiomyopathy (ACM) is primarily a familial disease with autosomal dominant inheritance. Incomplete penetrance and variable expression are common, resulting in diverse clinical manifestations. Although recent studies on genotype–phenotype relationships have improved our understanding of the molecular mechanisms leading to the expression of the full-blown disease, the underlying genetic substrate and the clinical course of asymptomatic or oligo-symptomatic mutation carriers are still poorly understood. We aimed to analyze different phenotypic expression profiles of ACM in the context of the same familial genetic mutation by studying nine adult cases from four different families with four different familial variants (two plakophilin-2 and two desmoglein-2) from the Swiss Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Registry. The affected individuals with the same genetic variants presented with highly variable phenotypes ranging from no disease or a classical, right-sided disease, to ACM with biventricular presentation. Moreover, some patients developed early-onset, electrically unstable disease whereas others with the same genetic variants presented with late-onset electrically stable disease. Despite differences in age, gender, underlying genotype, and other clinical characteristics, physical exercise has been observed as the common denominator in provoking an arrhythmic phenotype in these families.https://www.mdpi.com/2077-0383/9/11/3781arrhythmogenic cardiomyopathyphenotypegeneticsexercise |
| spellingShingle | Sarah Costa Alessio Gasperetti Argelia Medeiros-Domingo Deniz Akdis Corinna Brunckhorst Ardan M. Saguner Firat Duru Familial Arrhythmogenic Cardiomyopathy: Clinical Determinants of Phenotype Discordance and the Impact of Endurance Sports Journal of Clinical Medicine arrhythmogenic cardiomyopathy phenotype genetics exercise |
| title | Familial Arrhythmogenic Cardiomyopathy: Clinical Determinants of Phenotype Discordance and the Impact of Endurance Sports |
| title_full | Familial Arrhythmogenic Cardiomyopathy: Clinical Determinants of Phenotype Discordance and the Impact of Endurance Sports |
| title_fullStr | Familial Arrhythmogenic Cardiomyopathy: Clinical Determinants of Phenotype Discordance and the Impact of Endurance Sports |
| title_full_unstemmed | Familial Arrhythmogenic Cardiomyopathy: Clinical Determinants of Phenotype Discordance and the Impact of Endurance Sports |
| title_short | Familial Arrhythmogenic Cardiomyopathy: Clinical Determinants of Phenotype Discordance and the Impact of Endurance Sports |
| title_sort | familial arrhythmogenic cardiomyopathy clinical determinants of phenotype discordance and the impact of endurance sports |
| topic | arrhythmogenic cardiomyopathy phenotype genetics exercise |
| url | https://www.mdpi.com/2077-0383/9/11/3781 |
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