Dilated cardiomyopathy (DCM)

The inheritance pattern of dilated cardiomyopathy (DCM) is predominantly autosomal dominant, accounting for the majority of familial cases; however, expanding genomic studies in previously underrepresented populations have revealed a growing number of autosomal recessive forms.

It has been shown that only half of the DCM cases with an unclear cause are actually idiopathic DCM (IDCM) and are not caused indirectly by other primary diseases. Consequently, it is important to rule out secondary dilated cardiomyopathy as thoroughly as possible before genetic diagnosis is undertaken.

• In patients with suspected dilated cardiomyopathy (DCM), molecular genetic testing is an important part of the diagnostic work-up, particularly in idiopathic, familial, early-onset, or clinically suggestive cases. According to the , genetic testing, accompanied by pre- and post-test genetic counselling, is recommended as a key component of the clinical evaluation in patients with cardiomyopathy (Class I).
• A confirmed molecular diagnosis can establish the underlying aetiology, distinguish primary genetic DCM from secondary forms, and support a more precise disease classification. This is clinically relevant because DCM is genetically heterogeneous, and the affected gene may influence prognosis, surveillance, and management.
• Genetic findings can also contribute to risk stratification. Pathogenic variants in genes such as LMNA, FLNC, RBM20, PLN, DSP and other desmosomal genes may be associated with an increased risk of malignant ventricular arrhythmias and sudden cardiac death, sometimes out of proportion to left ventricular systolic dysfunction. In such cases, genetic information may support intensified rhythm monitoring and may influence consideration of ICD therapy beyond conventional LVEF-based criteria.
• Genetic testing is equally important for family management. Once a pathogenic or likely pathogenic germline variant has been identified in the index patient, targeted cascade testing can be offered to at-risk relatives. Genotype-positive relatives can enter structured cardiac surveillance, whereas genotype-negative relatives can often be discharged from long-term follow-up for that familial condition.
• Importantly, genetic results must be interpreted cautiously. Variants of uncertain significance should not be used for predictive testing or major clinical decisions. Careful assessment of gene–disease validity and variant pathogenicity is essential, as overinterpretation may lead to false-positive diagnoses and inappropriate clinical management.

• Hershberger RE, Jordan E. Dilated cardiomyopathy overview. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2024. PMID: .
• Zhang W, Qiu L, Cao Z, Xie J, Jin J, Bai R, et al. Systolic and diastolic blood pressure, abdominal obesity, and alcohol consumption contribute to the risk of hypertrophic and dilated cardiomyopathies in European and East Asian populations. BMC Med. 2025;23(1):692. PMID: .
• Mariani MV, Pierucci N, Fanisio F, Laviola D, Silvetti G, Piro A, et al. Inherited arrhythmias in the pediatric population: an updated overview. Medicina (Kaunas). 2024;60(1):94. PMID: .
• Arbelo E, Protonotarios A, Gimeno JR, Arbustini E, Barriales-Villa R, Basso C, et al. 2023 ESC Guidelines for the management of cardiomyopathies. Eur Heart J. 2023;44(37):3503-3626. PMID: .
• Hershberger RE, Givertz MM, Ho CY, Judge DP, Kantor PF, McBride KL, et al. Genetic evaluation of cardiomyopathy: a clinical practice resource of the American College of Medical Genetics and Genomics (ACMG). Genet Med. 2018;20(9):899-909. PMID: .
• Wilde AAM, Semsarian C, Márquez MF, Shamloo AS, Ackerman MJ, Ashley EA, et al. European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) expert consensus statement on the state of genetic testing for cardiac diseases. Europace. 2022;24(8):1307-1367. PMID: .