Quick Fire Cases
John A. Wells, IV, MD
Assistant Professor of Clinical Medicine
Vanderbilt University Medical Center
John A. Wells, IV, MD
Assistant Professor of Clinical Medicine
Vanderbilt University Medical Center
Satish Mishra, MD
Clinical Fellow, Advanced Cardiac Imaging
Vanderbilt University Medical Center
Jeff Dendy, MD
Assistant Professor of Medicine
Vanderbilt University Medical Center
Vanderbilt
Tania Ruiz M., MD
Assistant Professor of Medicine
Vanderbilt University Medical Center
Bruno B. Lima, MD, PhD
Assistant Professor of Medicine
Vanderbilt University Medical Center
Kristen George-Durrett, BSc
Research MRI Technologist
Vanderbilt University Medical Center
Sean G. Hughes, MD
Associate Professor of Clinical Medicine and Radiology
Director, Cardiac MRI and Advanced Cardiac Imaging Fellowship
Vanderbilt University Medical Center
Jonathan Soslow, MD, MSCI
Professor
Vanderbilt University Medical Center
Vanderbilt
David Parra, MD
Associate Professor
Vanderbilt University Medical Center
Identical twin 14-year-old girls, both manifesting carriers of a non-sense mutation in exon 35 of the dystrophin gene, presented to Vanderbilt’s pediatric Duchenne muscular dystrophy (DMD) multi-specialty clinic for evaluation.
The twins were born prematurely as part of a triplet birth. Their non-identical sister was not a DMD carrier. Although genetically identical, the girls exhibited differing disease severities. One sister had mild skeletal muscle weakness and was functionally independent, while the other sister had severe skeletal muscle weakness and was non-ambulatory. Neither patient showed any clinical cardiac involvement. Cardiac MRI (CMR) with contrast was ordered in both patients to assess for cardiac manifestations of DMD.
Both patients were scanned with a comprehensive CMR protocol, including standard tomographs, cardiac cines, parametric mapping (native T1, T2, and post-contrast T1), phase velocity flow mapping, and inversion recovery images at optimized inversion times on a Siemens 1.5T scanner using gadobutrol (Gadavist) contrast.
Both patients had normal LV and RV size and systolic function, with normal regional wall motion. Inversion recovery imaging revealed subepicardial late gadolinium enhancement (LGE) in both patients, suggesting myocardial fibrosis of the basal inferolateral wall without significant edema (Figures 1 and 2). The patient with milder skeletal muscle weakness had slightly higher mid-septal native T1, T2, and ECV values (Table 1) than her twin sister, suggesting more diffuse fibrosis.
DMD is a rare, X-linked disorder caused by loss-of-function mutations in the dystrophin gene. It is associated with severe morbidity and early mortality in affected males, most commonly due to respiratory and cardiac failure. Female carriers may exhibit phenotypic characteristics of DMD, including muscle weakness and cardiomyopathy. Female carriers of DMD-specific mutations show variable penetrance for the disease, and the spectrum of severity varies widely. The highlighted cases illustrate how disease severity can differ between genetically identical individuals. The cases also demonstrate that skeletal and cardiac involvement often do not correlate within the same patient, which is also observed in Duchenne and Becker muscular dystrophy.
Treatment with RAAS inhibitors has been shown to reduce the progression of fibrosis in male patients with DMD. Both patients in this case were started on treatment with lisinopril and eplerenone with plans for serial monitoring with CMR. Screening with CMR should be performed in all female DMD carriers, and those with positive findings should be referred to specialized centers, where available.
