P88 CARDIAC INVOLVEMENT IN FOUR NOVEL NESPRIN–1 GENETIC VARIANTS

Abstract Background Nesprins are proteins encoded by synaptic nuclear envelope (SYNE)–1 and –2 genes, that concur, together with lamin A/C emerin, to function. Almost 140 disease–related variants were identified, mostly resulting in central nervous system skeletal muscle disorders; only a few associated cardiomyopathy, relatively late onset no specific arrhythmic profile. Purpose To describe cardiac involvement 4 novel SYNE1 variants. Methods 189 patients underwent genetic analysis our center (2019–2022) for suspected cardiomyopathy (TruSight Cardio panel, Illumina); 72% had positive report, including pathogenic/likely pathogenic or of undetermined significance (VUS). Among them, (2%) males presented sole heterozygous VUS (figure). Results None neurological involvement. Patients 1 2 negative family history (FH) pacemaker implantation under 50 years old high–grade atrioventricular block (AVB). Transthoracic echocardiography (TTE) magnetic resonance (CMR) showed mildly impaired left ventricular ejection fraction (LVEF) without oedema fibrosis. During 3 6 follow–up (FU), several non–sustained episodes fast tachycardia (VT) atrial occurred. Patient is 55–year–old man FH bundle branch (LBBB) known since the age 45.In 2021, while playing football, he suffered arrest due fibrillation treated two DC shocks; ECG first–degree AVB LBBB; TTE CMR revealed LVEF A subcutaneous ICD was implanted, which recorded 1–year FU. 49–year–old man, sudden death (mother’s brothers at 40 years) polycystic kidney, who renal transplant. He anterior fascicular sustained monomorphic VT from right ventricle ablation. mild LV concentric hypertrophy normal LVEF, segmental abnormalities strain, Conclusions found be complex phenotype, early conduction disease, arrhythmias, cardiomyopathy. Further studies needed determine functional