Position StatementPosition Statement on the Diagnosis and Management of Familial Dilated Cardiomyopathy
Section snippets
Key Points
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Genetic factors have an important role in the pathogenesis of dilated cardiomyopathy (DCM) and can be a primary cause of disease.
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Clinical presentation: The clinical presentation of familial DCM can be variable. In most kindreds, affected individuals present with symptoms and signs attributable to left ventricular dysfunction. In some cases, the family phenotype may include additional cardiac or extra-cardiac manifestations, including conduction-system abnormalities or skeletal myopathy. These
Changes from 2013 Document
These guidelines have been revised overall with expanded sections on the molecular genetics of DCM and sequencing options for genetic testing. The document now includes recommendations for paediatric DCM.
1. Definition and Prevalence
Dilated cardiomyopathy (DCM) is a myocardial disorder characterised by dilatation and systolic dysfunction of the left ± right ventricles. It is one of the most common forms of heart muscle disease with an estimated prevalence of 1:2500 [1]. DCM can be caused by diverse conditions that promote cardiomyocyte injury or loss, including viral myocarditis, alcohol excess, and chemotherapeutic drugs. In approximately 50% of cases, an underlying cause is unable to be identified and the condition is
1. Familial DCM Disease Genes
Molecular genetics studies performed to date indicate that DCM is genetically heterogeneous with more than 40 genes associated with adult-onset familial and sporadic forms of disease [15]. These genes encode proteins in the cardiomyocyte sarcomere, cytoskeleton, sarcolemma, and nucleus, indicating pleiotropic molecular aetiologies. A similar spectrum of genetic mutations, including mitochondrial gene mutations, has been described in children with sporadic and familial DCM. The latter typically
1. Affected Individuals
Clinically-affected family members with DCM should receive standard pharmacological, device, and surgical management (circulatory support and transplantation) as indicated by the severity of symptoms and signs of heart failure, the electrocardiographic findings and the degree of left ventricular dysfunction. In families with DCM and conduction-system disease, young family members who present with conduction-system disturbances (sinus bradycardia, atrioventricular conduction block, ± atrial
Further Information
For further information about these guidelines, please contact Prof. Diane Fatkin, Molecular Cardiology Division, Victor Chang Cardiac Research Institute, PO Box 699, Darlinghurst NSW 2010; tel: +61 2 9295 8618; email: d fatkin@victorchang edu au.
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Cited by (11)
Diagnostic biomarkers of dilated cardiomyopathy
2021, ImmunobiologyCitation Excerpt :Results of an evidence-based assessment of genetic etiology of DCM indicated 51 genes with possible association with DCM, amongst which 12 genes showed definitive/strong association and 7 genes showed moderate association (Jordan et al., 2021). Familial DCM was traditionally defined by early onset (<35 years age) incidence of idiopathic DCM and/or unexplained death in two or more first-degree relatives (Fatkin et al., 2017). However, some diagnosed cases of sporadic DCM might be a representative of familial DCM and not matching the aforementioned criteria due to variable penetrance or small family size.
Inherited cardiomyopathies
2021, Clinical DNA Variant Interpretation: Theory and Practice: A Volume in Translational and Applied GenomicsFamilial Dilated Cardiomyopathy
2020, Heart Lung and CirculationCitation Excerpt :However, high-throughput next-generation sequencing has enabled the discovery of additional important genes, such as such as TTN, in which truncating variants are identified in ∼15–20% of DCM families [17], and genes such as RBM20 and FLNC that can be highly arrhythmogenic [18–20]. As the clinical utility of genetic information is increasingly recognised, a number of professional societies have updated practice guidelines for which patients need genetic testing [12,21–24]. In reality, testing practices differ with geographic location, access to services, and reimbursement.
Emerging role of microRNAs in dilated cardiomyopathy: evidence regarding etiology
2020, Translational ResearchCitation Excerpt :Recent studies have proposed that nearly 60% of DCM cases have a genetic cause.79 Nevertheless, the clinical presentation and phenotypic variation of familial DCM make its diagnosis complex.79-82 Indeed, approximately 25% of patients with idiopathic DCM are likely to have a genetic basis for disease.82
Precision Medicine in the Management of Dilated Cardiomyopathy: JACC State-of-the-Art Review
2019, Journal of the American College of CardiologyCitation Excerpt :By contrast, genetic test results are of considerable utility for assessing asymptomatic family members, allowing identification of those at risk of future disease and rationalization of follow-up. Genotype-positive, phenotype-negative family members need regular echocardiographic review to detect early signs of contractile dysfunction that may become apparent even before symptoms develop (19,20). There are no standard guidelines for the frequency of follow-up, and individualized plans need to be made based on the most recent echocardiographic findings and the typical age of onset of disease in the family.
Genome sequencing as a first-line genetic test in familial dilated cardiomyopathy
2019, Genetics in Medicine