Rapidly Progressive Heart Failure in a Female Carrier of Becker Muscular Dystrophy with No Skeletal Muscle Symptoms

Abstract

Becker muscular dystrophy (BMD) carriers are at risk to developing cardiac dysfunction. The prevalence of female BMD carriers remains underestimated, and the disease progression varies. We herein report the case of a young female BMD carrier who developed dilated cardiomyopathy (DCM) and heart failure without any skeletal muscle signs. Her cardiac dysfunction progressed over a mere two months, resulting in the need for left ventricular assist device implantation. Her case demonstrates that progressive cardiomyopathy can be the only clinical manifestation in some BMD carriers, suggesting the need for a more aggressive implementation of genetic testing in female DCM patients.

Modeling Reduced Contractility and Stiffness Using iPSC-Derived Cardiomyocytes Generated From Female Becker Muscular Dystrophy Carrier

“…We encountered a rare case of a 29-year-old female BMD carrier (proband, Ⅲ-4) ( Figure 1A ) with rapidly progressive severe HF who underwent LVAD implantation. 16 Echocardiography at 29 years of age revealed a visibly enlarged left ventricle and severe diffuse LV hypokinesis with an ejection fraction of 17% ( Figure 1B ). In the family history, her paternal grandmother (Ⅰ-2) died of HF in her 80s, and a paternal relative (Ⅱ-4) had a diagnosis of muscular dystrophy.…”

“…In the current study, we encountered a young female BMD carrier with an in-frame deletion in DMD of exon 45-48 (Δ45-48) who developed early onset DCM with severe advanced HF that required implantation of an LV assist device (LVAD). 16 We determined the proportion of the XCI state in the proband’s LV myocardium and identified a potential second-hit variant in the proband that was not present in her nonmanifesting sister. To determine the pathologic effect of the genetic variants, we also performed functional analysis using self-organized tissue rings (SOTRs) generated from isogenic iPSC-CMs prepared using the XCI state and genome editing.…”

MicroRNAs in Dystrophinopathy

“…These data indicate a pathological role of elevated miR-339-5p in DMD cardiomyocytes [59]. Serum miRNAs in disease carriers: Even without skeletal muscle symptoms, heart symptoms often occur in female DMD/BMD carriers for the asymptomatic form with mild abnormalities to progressive heart failure [60] and dilated cardiomyopathy [61], which may require heart transplantation [62]. Therefore, early detection of heart disease in female carriers is important.…”