Cardiomyopathy in a Duchenne Muscular Dystrophy Carrier and Her Diseased Son
Similar Pattern Revealed by Cardiovascular MRI
A 14-year-old boy with Duchenne muscular dystrophy (DMD; duplication of dystrophin gene exons 8 to 11), accompanied by his mother, was brought to our hospital to undergo a comprehensive cardiac study as a participant in our ongoing research project on patients with muscular dystrophy (to evaluate the presence and presentation pattern of cardiomyopathy). He had lost ambulation at the age of 9 and used a wheelchair. He had undergone annual cardiac examinations by echocardiography, which to that date had been without any pathological finding. He described of minor dyspnea on exertion and transient palpitations occurring infrequently. His resting ECG (Figure 1A) demonstrated negative T waves in leads V1 through V3. Blood analysis revealed an elevated total creatine kinase level of 2630 U/L (normal <190 U/L), a slightly elevated creatine kinase-MB fraction level of 80 U/L (normal <25 U/L), an elevated troponin T level of 0.09 ng/mL (normal <0.03 ng/mL), and a normal N-terminal pro-brain natriuretic peptide level of 137 pg/mL (normal <450 pg/mL).
Because of the patients’ scoliosis, the acoustic window during echocardiography was limited, and only parasternal views with normal findings could be obtained with acceptable image quality (Movies I and II in the online-only Data Supplement). Then, cardiovascular MRI (CMR) was performed on a clinical scanner (1.5 Tesla Sonata, Siemens, Germany). The CMR cine images demonstrated slightly reduced left ventricular (LV) systolic function (ejection fraction 52%) with regional hypokinesia in the inferolateral wall (Figure 2A, upper and middle panels; Movies III to IV, full-motion images in the online-only Data Supplement). Contrast imaging was performed after intravenous application of 0.15 mmol/kg gadopentetate-meglumine (Magnograf) by use of an inversion-recovery gradient-echo technique. Late gadolinium enhancement indicative of myocardial damage was detected in the subepicardium of the left ventricular inferolateral wall (Figure 2A). Such a late gadolinium enhancement pattern was recently described in patients with muscular dystrophy1,2; however, the exact underlying pathomechanism for such a distribution of myocardial damage in muscular dystrophy patients is still unclear.2 Nevertheless, as exemplarily demonstrated in Figure 3, cardiomyopathy in such patients is typically associated with (1) the macroscopic finding of a subepicardial distribution of late gadolinium enhancement in the inferolateral wall and (2) a lack or reduction of dystrophin protein in cardiomyocytes when endomyocardial biopsy samples taken from the site of late gadolinium enhancement are analyzed.
The patient’s mother, a 44-year-old DMD carrier in good general condition and without skeletal myopathy, reported that she occasionally experienced palpitations, but so far she had not undergone any cardiovascular studies. Inasmuch as cardiomyopathy had been described previously in muscular dystrophy carrier patients,3,4 we decided to include her in our research project and to perform the same studies. Her resting ECG (Figure 1B) demonstrated diffuse ST-T changes in leads I through III, aVF and V4–V6. Blood analysis revealed an elevated total creatine kinase level of 220 U/L (normal <190 U/L) but normal values for creatine kinase-MB fraction, troponin T, and N-terminal pro-brain natriuretic peptide. Echocardiography could be performed with a good acoustic window and was suggestive of a mildly reduced left ventricular systolic function with a hypokinetic inferolateral wall (Movies V and VI in the online-only Data Supplement). The CMR cine images confirmed a severe hypokinesia in the inferolateral wall similar to the finding in her son (Figure 2B and Movies VII and VIII in the online-only Data Supplement), and volumetric analysis resulted in a left ventricular ejection fraction of only 45%. Again, contrast images were performed after intravenous application of 0.15 mmol/kg gadopentetate-meglumine (Figure 2B) and revealed exactly the same pattern of myocardial damage as was observed in her son. Hence, cardiomyopathy was diagnosed in both the DMD carrier mother and her son on the basis of the CMR study results, and both were prescribed an angiotensin-converting enzyme inhibitor and scheduled for follow-up.
Contradictory studies of patients with DMD carrier status concerning the presence and clinical course of cardiomyopathy have been published.3–6 This case report is unique because it demonstrates for the first time, as far as we are aware, the presence of the same pattern of myocardial damage (detected by CMR cine and contrast imaging) in a DMD patient and his DMD carrier mother, thereby clearly indicating that MD carriers may be prone to cardiomyopathy. Our observation suggests that cardiac studies for evaluation of cardiomyopathy, including CMR, should be performed both in patients with MD and in their carrier mothers. This case also illustrates the influence of genetic disorders with respect to the presence, pattern, and severity of cardiomyopathy; even a heterozygous genetic constitution (such as a duplication of dystrophin gene exons 8 to 11 on 1 X chromosome in this DMD carrier mother) may result in severe cardiomyopathy.
Sources of Funding
This work was financially supported by a grant from the German Heart Foundation (Deutsche Stiftung für Herzforschung; grant-ID F/15/07 to A.Y.).
The online-only Data Supplement is available with this article at http://circ.ahajournals.org/cgi/content/full/121/10/e237/DC1.