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Genetic Screening Reveals Heterogeneous Clinical Phenotypes in Patients with Dilated Cardiomyopathy and Troponin T2
Angelika Weis1, Svenja Krueck1, Gregor Dombrowsky2,3
1Department of Pediatric Cardiology, Intensive Care Medicine and Congenital Heart Disease, Justus Liebig University Giessen, 35390 Giessen, Germany.
Insights
Genetic screening for dilated cardiomyopathy (DCM) in families with TNNT2 variants improves risk assessment and enables timely interventions, particularly for asymptomatic relatives. Early detection leads to better patient outcomes.
Area of Science:
- Cardiovascular Genetics
- Genetic Cardiology
- Molecular Cardiology
Background:
- Cardiomyopathies (CMs) represent a severe, heterogeneous group of cardiac diseases with variable phenotypes.
- Dilated cardiomyopathy (DCM) affects approximately 1 in 100,000 individuals.
- Routine genetic screening of family members for CMs is not standard practice.
Purpose of the Study:
- To evaluate the impact of genetic screening in families with DCM caused by TNNT2 gene variants.
- To assess the clinical utility of identifying pathogenic variants for risk stratification and management.
- To highlight the importance of family screening in improving outcomes for DCM patients.
Main Methods:
- Analysis of three families with DCM and pathogenic variants in the troponin T2, Cardiac Type (TNNT2) gene.
- Collection of detailed pedigrees and clinical data from affected individuals.
- Assessment of variant penetrance, age of onset, and clinical outcomes.
Main Results:
- Pathogenic TNNT2 variants demonstrated high penetrance and led to poor outcomes, with 8 of 16 patients experiencing death or heart transplantation.
- The age of onset for DCM symptoms ranged widely, from the neonatal period to 52 years.
- Some patients experienced rapid progression to acute heart failure and severe decompensation.
Conclusions:
- Family screening in DCM patients significantly enhances risk assessment, especially for asymptomatic relatives.
- Screening facilitates timely and appropriate treatment, including heart failure medication and pulmonary artery banding.
- Systematic genetic evaluation of families with DCM improves management strategies and patient prognosis.
Background:
Cardiomyopathies (CMs) are a heterogeneous and severe group of diseases that shows a highly variable cardiac phenotype and an incidence of app. 1/100.000. Genetic screening of family members is not yet performed routinely.
Patients And Methods:
Three families with dilated cardiomyopathy (DCM) and pathogenic variants in the troponin T2, Cardiac Type (TNNT2) gene were included. Pedigrees and clinical data of the patients were collected. The reported variants in the TNNT2 gene showed a high penetrance and a poor outcome, with 8 of 16 patients dying or receiving heart transplantation. The age of onset varied from the neonatal period to the age of 52. Acute heart failure and severe decompensation developed within a short period in some patients.
Conclusion:
Family screening of patients with DCM improves risk assessment, especially for individuals who are currently asymptomatic. Screening contributes to improved treatment by enabling practitioners to set appropriate control intervals and quickly begin interventional measures, such as heart failure medication or, in selected cases, pulmonary artery banding.
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Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which...