Case Report: Simultaneous presentation of end-stage heart failure with cardiogenic shock requiring emergency transplantation in monozygotic twins with myofibrillar myopathy: a previously unknown genetic disease?

We report the rare case of 16-year-old male monozygotic twins, born to first cousins, who developed acute end-stage heart failure due to dilated cardiomyopathy, requiring emergency heart transplantations within days of each other. Both twins presented with rapid-onset symptoms and progressed to refractory cardiogenic shock despite inotropic support, necessitating venoarterial extracorporeal membrane oxygenation. Heart transplantation was performed within 3 weeks of admission, and both twins have remained clinically stable 3 years posttransplantation. Family history was negative for cardiomyopathy. Genetic testing identified the following four shared variants: a homozygous FLNC variant (p.Tyr786Asp), two heterozygous SCN5A variants (p.Gln1366His and p.Thr1367Ser), and a heterozygous MYH7 variant (p.Ile1927Phe). All were classified as variants of uncertain significance. Segregation analysis showed that both parents were heterozygous carriers of the FLNC variant; their daughter (the twins’ sister) was homozygous for FLNC and carried both SCN5A variants; however, she was asymptomatic. A muscle biopsy from one twin showed pathological features consistent with a diagnosis of myofibrillar myopathy, including fiber disarray and desmin accumulation. In silico analysis suggested structural disruption associated with the MYH7 variant. This case likely represents an unclassified genetic cardiomyopathy with skeletal and cardiac muscle involvement. It underscores the diagnostic complexity of consanguineous pedigrees and the limitations of current variant classification systems. The synchronous disease onset in these monozygotic twins suggests a potential genetic or epigenetic trigger and highlights the value of integrating family studies, histopathology, and computational modeling in the evaluation of inherited cardiomyopathies.