Simultaneous PresentaƟon of End-stage Heart Failure With Cardiogenic Shock Requiring Emergency TransplantaƟon in MonozygoƟc Twins With Myofibrillar Myopathy: a Previously Unknown GeneƟc Disease?

Giovanni Battista Luciani¹Cristina Panico^2*Antonella Galeone^1*Vittoria Medeghini²Matteo Ciuffreda³Rossana Mineri²Livio San Biagio³Paola Tonin³Gaetano Nicola Vattemi¹Stilijan Hoxha³Alessandra Francica³Gina Mazzeo¹Alessia Gambaro³Leonardo Gottin¹Giuseppe Faggian¹Francesco Onorati¹Elisa Di Pasquale²

• ¹University of Verona, Verona, Italy
• ²IRCCS Humanitas Research Hospital, Rozzano, Italy
• ³Azienda Ospedaliera Universitaria Integrata Verona, Verona, Italy

We report a rare case of 16-year-old monozygotic male twins, born to first cousins, who developed acute end-stage heart failure due to dilated cardiomyopathy, requiring emergency heart transplantation within days of each other. Both twins presented with rapid-onset symptoms and progressed to refractory cardiogenic shock despite inotropic support, necessitating veno-arterial extracorporeal membrane oxygenation. Heart transplantation was performed within three weeks of admission, and both twins remain clinically stable three years post-transplantation. Family history was negative for cardiomyopathy. Genetic testing identified 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 both parents to be heterozygous carriers of the FLNC variant; their daughter (the twins' sister) was homozygous for FLNC and carried both SCN5A variants, yet was asymptomatic. 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 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.