Arrhythmogenic Cardiomyopathy: A Disease or Merely a Phenotype?

Protonotarios, Alexandros; Elliott, Perry

doi:10.15420/ecr.2019.05

Cited by 18 publications

(21 citation statements)

References 60 publications

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“…Таким образом, в связи с расширением спектра наблюдаемых фенотипов и для систематизации новых патогенетических знаний с клиническими доказательствами современной концепции о патологическом вовлечении обоих желудочков при АПЖК, понадобилась смена парадигмы АКМП. Если в литературных данных первоначально сообщалось об исследованиях, которые демонстрировали (при аутопсии) вовлечение ЛЖ с фиброзно-жировым замещением миокарда в 76% случаев АПЖК [6,7], то в не давних работах авторы заявили о гистопатологических признаках поражения ЛЖ у 87% умерших пациентов с АПЖК [20][21][22][23]. Смена парадигмы АКМП обусловлена также обнаружением новых генов, детерминирующих похожие аритмические фе нотипы, и изучением множества других подтипов, обусловленных не только генетическими причинами, но и другими приобретенными факторами (саркоидоз, миокардит).…”

Section: литература/Referencesunclassified

A paradigm shift in the concept of arrhythmogenic cardiomyopathy: expanding the clinical and genetic spectrum, new diagnostic criteria for left ventricular phenotypes

et al. 2020

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Recent multicenter studies using high-tech cardiac imaging and novel translational technologies have shown that cardiac fibrofatty replacement, characteristic of arrhythmogenic cardiomyopathy (ACM), is observed in both ventricles; left ventricular (LV) involvement may be minimal, on par with the right ventricle (RV), or dominant. In 2019, the Heart Rhythm Society (HRS) proposed a new approach to the assessment of arrhythmic and genetic diseases with the inclusion of new phenotypes — left-dominant ACM and biventricular ACM. In 2020, to improve the diagnosis of left ventricular phenotypes, European experts revised ACM criteria (based on the 2010 ITF criteria), which are called the Padua criteria.The presented article highlights the clinical and genetic aspects of the new concept and the difficulties in ACM diagnosis, the practical experience of using new diagnostic algorithm. To help practitioners, step-by-step differential diagnosis and risk stratification of right and left ventricular phenotypes are presented using clinical examples (leftdominant ACM with a pathogenic variant in the LMNA gene; right-dominant ACM associated with a desmoplakin gene mutation, with predominant RV and moderate LV involvement; and an isolated RV ACM associated with a mutation in the plakophilin 2 gene).

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Section: литература/Referencesunclassified

A paradigm shift in the concept of arrhythmogenic cardiomyopathy: expanding the clinical and genetic spectrum, new diagnostic criteria for left ventricular phenotypes

et al. 2020

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“…Even dominant left ventricular forms have been described [ 29 ], indicating an overlap between arrhythmogenic DCM and ARVC. Despite precise clinical definitions of ACM, this term is therefore more frequently used in the newer literature [ 30 ]. Progressive replacement of the myocardium against fibrotic and fatty tissue at the cellular and histological level is characteristic for ACM [ 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset

Brodehl

Мешков

Myasnikov

et al. 2021

IJMS

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About 50% of patients with arrhythmogenic cardiomyopathy (ACM) carry a pathogenic or likely pathogenic mutation in the desmosomal genes. However, there is a significant number of patients without positive familial anamnesis. Therefore, the molecular reasons for ACM in these patients are frequently unknown and a genetic contribution might be underestimated. Here, we used a next-generation sequencing (NGS) approach and in addition single nucleotide polymor-phism (SNP) arrays for the genetic analysis of two independent index patients without familial medical history. Of note, this genetic strategy revealed a homozygous splice site mutation (DSG2–c.378+1G>T) in the first patient and a nonsense mutation (DSG2–p.L772X) in combination with a large deletion in DSG2 in the second one. In conclusion, a recessive inheritance pattern is likely for both cases, which might contribute to the hidden medical history in both families. This is the first report about these novel loss-of-function mutations in DSG2 that have not been previously identi-fied. Therefore, we suggest performing deep genetic analyses using NGS in combination with SNP arrays also for ACM index patients without obvious familial medical history. In the future, this finding might has relevance for the genetic counseling of similar cases.

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“…Genotype-positive individuals more commonly present with ventricular arrhythmias at a younger age [30]. We also know that patients with pathogenic genetic variants coding for nondesmosomal proteins such as transmembrane protein 43, phospholamban, and lamin A/C seem to be at higher risk for arrhythmia than patients with desmosomal gene variants [31]. Individuals with pathogenic genetic variants in desmoglein-2 is more prone to heart failure than those with variants in PKP2 [32].…”

Section: Discussionmentioning

confidence: 99%

Genetic Variant Score and Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Plakophilin-2 Mutation Carriers

et al. 2021

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Introduction: Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (PKP2). Methods: CADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia/ventricular fibrillation (VT/VF) or syncope and age at definite ARVC diagnosis were Anneli Svensson and Pyotr G. Platonov contributed equally.

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Arrhythmogenic Cardiomyopathy: A Disease or Merely a Phenotype?

Cited by 18 publications

References 60 publications

A paradigm shift in the concept of arrhythmogenic cardiomyopathy: expanding the clinical and genetic spectrum, new diagnostic criteria for left ventricular phenotypes

A paradigm shift in the concept of arrhythmogenic cardiomyopathy: expanding the clinical and genetic spectrum, new diagnostic criteria for left ventricular phenotypes

Hemi- and Homozygous Loss-of-Function Mutations in DSG2 (Desmoglein-2) Cause Recessive Arrhythmogenic Cardiomyopathy with an Early Onset

Genetic Variant Score and Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Plakophilin-2 Mutation Carriers

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