Significance of genetic testing in personalized approach of dilated cardiomyopathy: case report

35 years old male presented to a cardiology department due to an episode of dyspnea. He denied any chest pain, palpitations or syncope. Previous medical history was unremarkable. However, his niece died suddenly at the age of five years. She was diagnosed with dilated cardiomyopathy (DCM) since she was three months. Patient’s mother died during pregnancy at the age of 33 due to unclear reason. No genetic analysis or family screening was performed. Patient underwent comprehensive investigation. Echocardiography showed dilation of left ventricle (LV EDD 82-88 mm) and atrium (LAVI 50 ml/m2) with diffuse hypokinesia and severely reduced ejection fraction (EF 20%). Coronary angiography revealed no stenotic lesions. Cardiac magnetic resonance imaging showed LV dilation, diffuse hypokinesia, reduced EF (18%) and increased extracellular volume (ECV 36%). Frequent polymorphic premature ventricular complexes (150-200 per hour) and 7 episodes of short non-sustained ventricular tachycardia (NSVT) were recorded during 24-hour Holtermonitoring. Based on investigation and family history diagnosis of hereditary DCM was made. Due to high suspicion of genetic aetiology, next generation sequencing of comprehensive cardiology panel (217 genes) and mitochondrial genome was performed. Test revealed likely pathogenic variant TTN c.82240C>T, p.(Arg27414*) and variant of uncertain significance in TPM1 c.725C>T, p.(Ala242Val). TPM1 variant is considered to be causative as well, but segregation analysis of the family is needed. It is established that presence of more than one pathogenic or likely pathogenic variants in DCM carries higher risk of sudden cardiac death (SCD). Taking into account presence of NSVT and high-risk genetic background, patient underwent implantation of cardiovetrer-defibrilator for primary prevention of SCD. Cascade screening of the family is ongoing. This clinical case shows a rare case of DCM in a patient with two causative genetic variants as well as importance of genetic testing in personalized management of inherited cardiomyopathies.