Challenges of genetics in the diagnosis of sudden cardiac death. Interest of forensic and legal medicine

Medicina Clínica (English Edition), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

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PRKAG2 Syndrome: Clinical Features, Imaging Findings and Cardiac Events

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 751 - 751

Published: March 19, 2025

Background/Objectives: PRKAG2 syndrome (PS) is a rare genocopy of hypertrophic cardiomyopathy (HCM). Our goal was to expand knowledge about PS by analyzing patient clinical, imaging, and follow-up data. Methods: The study included carriers likely pathogenic or variants identified in the years 2011–2022. Cardiac involvement assessed electrocardiography, echocardiography, cardiac magnetic resonance endomyocardial biopsy (EMB). We recorded concomitant diseases events, including implantation electronic devices, arrhythmia, heart failure (HF), death. Results: Seven patients from four families (median age 43 years) with variants: Phe293Leu, Val336Leu, Arg302Gln, His530Arg were included. At first evaluation, 3 New York Heart Association (NYHA) functional class II–III, while remaining NYHA I. Left ventricular hypertrophy (LVH) present 5 patients; 2 had pre-excitation, one atrial flutter pacemaker-dependent; bradycardia. Two female chronic renal disease. In EMB patients, staining for glycogen deposits positive. Furthermore, we provide link between Val336Leu variant autophagy on EMB. After median 13.1 years, 6 LVH, required admission HF, 1 sustained tachycardia subsequent cardioverter defibrillator implantation, despite this, died suddenly; there two de novo pacemaker implantations due symptomatic Conclusions: PR distinctive disorder an early onset arrhythmic often leading HF.

Language: Английский

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Variant sub-tiering, disease-gene associations and strictness of clinical criteria improves the interpretation of variants of uncertain significance in hereditary cardiomyopathies and rhythm disorders

Journal of Human Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 30, 2025

Language: Английский

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Medically Actionable Secondary Findings from Whole-Exome Sequencing (WES) Data in a Sample of 3972 Individuals

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3509 - 3509

Published: April 9, 2025

The application of whole-exome sequencing (WES) for diagnostic purposes has the potential to unravel secondary findings unrelated with primary reason testing. Some those might be high clinical utility and comprise disease-causing variants in genes, related life-threatening clinically actionable diseases. Clarifying allelic frequencies such specific populations is a crucial step large-scale deployment genomic medicine. We analysed medically relevant 81 genes from American College Medical Genetics Genomics (ACMG) v3.2 list loci, using WES data laboratory cohort 3972 persons, tentatively resampled represent Portuguese population geographic distribution. identified 6.2% our cohort, distributed across several disease domains: cardiovascular disorders (3.0%), cancer predisposition (2.0%), miscellaneous (1.1%), metabolic (0.1%). Additionally, we estimated frequency heterozygotes recessive alleles 11.1%. Overall, results suggest that can approximately persons population. This first study estimating Portugal. These provide valuable insight patients, healthcare providers, policymakers involved advancing medicine at national international level.

Language: Английский

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High incidence of malignant arrhythmias and heart failure in patients with RBM20-associated cardiomyopathy: A multicenter cohort study and review of the literature

International Journal of Cardiology, Journal Year: 2025, Volume and Issue: unknown, P. 133350 - 133350

Published: May 1, 2025

Language: Английский

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ANMCO position paper ‘Hypertrophic cardiomyopathy: from diagnosis to treatment’

European Heart Journal Supplements, Journal Year: 2025, Volume and Issue: 27(Supplement_5), P. v256 - v279

Published: May 1, 2025

Hypertrophic cardiomyopathy (HCM) is a non-rare genetic cardiomyopathy, with an estimated prevalence of 1:500, characterized by increase in the left ventricular wall thickness absence increased loading conditions. The hypertrophy mostly asymmetric and predominantly affects basal septum anterior wall. Left outflow tract obstruction, at rest or after provocative tests, detected many patients represents primary cause reduced functional capacity, as well independent predictor sudden cardiac death advanced heart failure. Until ∼1 year ago, symptomatic despite maximal therapy β-blockers calcium channel blockers plus disopyramide had only septal reduction through myectomy alcoholization additional therapeutic options. Today, new class drugs that inhibit myosin activity available for obstructive HCM. In light treatment perspectives, correct clinical-therapeutic classification affected becomes fundamental importance cardiologist. aim this position paper to knowledge cardiologists field HCM, defining its epidemiological, genetic, pathological characteristics, identifying diagnostic criteria instrumental methods capable stratifying risk profile, optimal tailored on single patient.

Language: Английский

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Cascade genetic counseling and testing in hereditary syndromes: inherited cardiovascular disease as a model: a narrative review

Familial Cancer, Journal Year: 2024, Volume and Issue: 23(2), P. 155 - 164

Published: Jan. 6, 2024

Abstract Inherited cardiovascular diseases cover the inherited disease familial hypercholesterolemia and cardiac diseases, like cardiomyopathies arrhythmia syndromes. Cascade genetic counseling testing in have had three decades of academic attention. affect around 1–2% population worldwide cascade are considered valuable since preventive measures and/or treatments available. via a family-mediated approach leads to an uptake among at-risk relatives 40% one year after identification causal variant proband, with remaining far from complete on long-term. These findings align rates for other late onset medically actionable hereditary cancer Previous interventions increase focused optimizing process informing through proband contacting directly. However, despite successful information dissemination relatives, these approaches little or no effect uptake. The limited research into barriers that impede seeking has revealed knowledge, attitudinal, social practical but it remains unknown how factors contribute decision-making relatives. A significant only been reached setting hypercholesterolemia, where active provision was accompanied by reduction health-system-related barriers. We propose more is needed -including barriers- they hinder so can be optimized (adjusted) interventions.

Language: Английский

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Unveiling the Spectrum of Minor Genes in Cardiomyopathies: A Narrative Review

Published: July 25, 2024

Hereditary cardiomyopathies (CMPs), including Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC), Dilated (DCM), and Hypertrophic (HCM), represent a group of heart disorders that significantly contribute to cardiovascular morbidity mortality are often driven by genetic factors. Recent advances in Next-Generation Sequencing (NGS) technology have enabled the identification rare variants both well-established minor genes associated CMPs. Nowadays, set core is included diagnostic panels for ARVC, DCM, HCM. On other hand, despite their lesser-known status, may disease mechanisms influence prognosis. This review evaluates current evidence supporting involvement CMPs, considering potential pathogenicity clinical significance. A comprehensive analysis databases such as ClinGen, ClinVar, GeneReviews, along with recent literature guidelines, provides thorough overview landscape CMPs offers insights future research translation practice. Given increasing knowledge on these less-understood factors, studies essential clearly assess roles, ultimately leading improved precision therapeutic strategies hereditary

Language: Английский

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Prequalification of genome-based newborn screening for severe childhood genetic diseases through federated training based on purifying hyperselection

The American Journal of Human Genetics, Journal Year: 2024, Volume and Issue: 111(12), P. 2618 - 2642

Published: Dec. 1, 2024

Language: Английский

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Unveiling the Spectrum of Minor Genes in Cardiomyopathies: A Narrative Review

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(18), P. 9787 - 9787

Published: Sept. 10, 2024

Hereditary cardiomyopathies (CMPs), including arrhythmogenic cardiomyopathy (ACM), dilated (DCM), and hypertrophic (HCM), represent a group of heart disorders that significantly contribute to cardiovascular morbidity mortality are often driven by genetic factors. Recent advances in next-generation sequencing (NGS) technology have enabled the identification rare variants both well-established minor genes associated with CMPs. Nowadays, set core is included diagnostic panels for ACM, DCM, HCM. On other hand, despite their lesser-known status, may disease mechanisms influence prognosis. This review evaluates current evidence supporting involvement CMPs, considering potential pathogenicity clinical significance. A comprehensive analysis databases, such as ClinGen, ClinVar, GeneReviews, along recent literature guidelines provides thorough overview landscape CMPs offers guidance practice, evaluating each case individually based on referral, insights future research. Given increasing knowledge these less understood factors, studies essential clearly assess roles, ultimately leading improved precision therapeutic strategies hereditary

Language: Английский

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