Secondary Logo

Journal Logo


Duchenne muscular dystrophy and dilated cardiomyopathy with deletion of exon 45 and 49

Zhuang, Xinyu1; Luo, Sushan2; Fan, Huihua3; Zhang, Jinjin3; Chen, Hua3; Yan, Pingping3; Bao, Liwen1,∗

Author Information
doi: 10.1097/CP9.0000000000000006
  • Open



Duchenne muscular dystrophy (DMD) is an X-linked degenerative disease resulting in progressive weakness[1]. DMD is caused by mutations in the dystrophin gene, the largest gene in the human genome[2]. The dystrophin protein forms a transmembrane link between the sarcomere and the extracellular matrix, glycoproteins, as well as sarcoglycans[3]. DMD typically manifests itself in early childhood (the average age upon initial diagnosis: 4 years), and progresses quickly. Severe cardiomyopathy generally manifests at about 10 years of age and is prevalent in most patients by 20 years of age[4]. Life expectancy has increased with medical treatment[1]. Still there is no cure for DMD. Dilated cardiomyopathy (DCM) is the major cause of morbidity and mortality[5].

Here we reported a case of a young man with genetically confirmed DMD. Key features included skeletal muscle weakness in early childhood and subsequent severe DCM.

Case presentation

A 26-year-old presented with paroxysmal chest pain and systemic edema that started 2 years earlier and worsened during the past 2 months. Past history was uneventful until January 2014 when a diagnosis of hepatitis was made. In fact, he went to the hospital because of abdominal pain and was diagnosed in the department of gastroenterology in a local hospital. He then developed symptoms and signs indicative of heart failure, and was diagnosed as having DCM. He denied abuse of any drug (including alcohol) and allergy, and disclosed no family history of major cardiovascular diseases.

Auscultation revealed diastolic rumbling murmur (level 3/6) in the apical region and no inspiratory crackles. Symmetric muscle atrophy was evident in the thighs and legs. Muscle strength of proximal hip flexion and knee extension was grade 3. The posterior muscle groups of the leg were slightly hypertrophic. Moderate edema was noticed in both legs. Muscle strength in the upper limbs was normal (grade 5).

Laboratory workup showed hyperbilirubinemia with elevated total bilirubin (47.8 μmol/L; normal range 3.4–20.4 μmol/L) and direct bilirubin (37.6 μmol/L; normal range <5 μmol/L), serum pro-brain-natriuretic peptide (pro-BNP) (8,839.0 pg/mL; normal range <300 pg/mL), troponin I (cTnI) (0.084 ng/mL; normal range 0.013–0.025 ng/mL), myoglobin (255.7 ng/mL; normal range 28–72 ng/mL), and creatine kinase-MB (CK-MB) (1,164 U/L; normal range 50–310 U/L).

An electrocardiogram (ECG) showed sinus rhythm, I° atrioventricular block (AVB), and intra-ventricular block (Figure 1). Echocardiography showed 30% left ventricular EF, an enlarged heart, and moderate mitral regurgitation. The patient was treated with spironolactone and torasemide to reduce preload. Digoxin, perindopril, and sustained-release metoprolol were also used. Sodium bicarbonate was used to manage hyperuricemia, and ursodeoxycholic acid was used to control cholecystitis.

Figure 1:
Twelve-lead electrocardiogram: sinus rhythm, I° intra-ventricular block, I° atrioventricular block.

Upon further inquiry after hospitalization, the patient disclosed that muscle weakening started at 7 years of age. MRI, electromyography (EMG) of the lower limbs, and muscle biopsy indicated myogenic damage. A diagnosis of muscular dystrophy was made upon discharge from the hospital with improved symptoms and signs.

Three weeks later, the patient presented again with a worsening condition. Blood biochemistry showed similar findings to the initial presentation. ECG revealed I °AVB, left anterior branch block, as well as ST segment and T wave inversion. Holter monitoring revealed short episodes of ventricular tachycardia (<1% during 24 hours). Coronary CTA showed no lesions. On echocardiography, the abnormalities seemed more severe than upon the initial presentation. In addition to heart enlargement and moderate mitral regurgitation, echocardiography showed pulmonary hypertension (54 mm Hg), mild/moderate tricuspid regurgitation, and widened inferior vena cava. LVEF, as measured by bi-plane Simpson method, was 32% (Figure 2).

Figure 2:
Echocardiography: dilation and impaired contraction of the left ventricle and the right ventricle. A, LV contractile dysfunction. B, heart enlargement.LV: left ventricle; RV: right ventricle.

MRI revealed severe atrophy of the muscles in the thigh (except for sewing and thin muscles) and the calf (except for anterior muscles), and replacement by adipose tissue (Figure 3). EMG revealed myogenic damage corresponding with myoelectrical changes. Some of the muscles examined showed fibrillation potential or compound repetitive discharge. The unit potential of light contraction exercise showed multi-phase potential, increased irregular waves, and narrowed unit potential of exercise. Re-contraction showed early recruitment changes. Biopsy and genetic testing showed mutation of the dystrophin gene (deletion of exons 45 and 49 (Figures 4 and 5). A diagnosis of DMD and DCM was made, and the patient was treated with digoxin, spironolactone, torasemide, metoprolol, perindopril, ursodeoxycholic acid, sodium bicarbonate, and bicyclol. After symptoms alleviation, he was discharged. He survived for two more years, during which his general condition and heart failure deteriorated progressively (timeline in Table 1).

Figure 3:
MRI: thigh muscles, except for sewing and thin muscles, were replaced by adipose tissue. A, Transverse section; B, Coronal section.
Figure 4:
Left biceps muscle biopsy and genetic testing. A, H&E staining: Muscle fibers varied in size, increased fat cells, and muscle dystrophy, 200×; B and C, Immunohistochemical staining: partial deletion of R-dystrophin and D-dystrophin, NADH method, 200×; D, dysferlin immunohistochemical staining: no significant muscle destruction, 200×.
Figure 5:
It was found that the DMD gene (NM_004006) of the sample had e xon45-exon49 deletion, which may be pathogenic. A, exon 49 deletion; B, exon 45 deletion.
Table 1 - Timeline
Date Symptoms and signs Diagnostic tests Interventions
2014.1 Abdominal pain Not available Chinese medicine treatments
2014.4 Whole body edema Echocardiography: Dilated cardiomyopathy Spironolactone, Digoxin, Torasemide, Metoprolol
2016.3.15 Worsening symptoms Echocardiography, Electrocardiogram Heart failure therapy and pain relief treatment
2016.3.29 Chest pain, edema Electromyography, limb magnetic resonance imaging, muscle biopsy, Holter Spironolactone 20 mg qd, Digoxin 0.125 mg qd, Torasemide 5 mg bid, Perindopril 4 mg qd, Betaloc 142.5 mg qd
2016.4.20 Recurrent chest pain and edema Echocardiography, chest X-ray Spironolactone 20 mg bid, Digoxin 0.125 mg qd, Torasemide 5 mg bid, Betaloc 71.25 mg qd, trimetazidine 50 mg bid
2018 Final follow-up Death

Review and discussion

Muscular dystrophy (MD) is a group of inheritable diseases that cause progressive weakness of skeletal muscles. In addition to skeletal muscles, the myocardium could also be involved in MD[6]. The most common forms of MD are DMD and Becker muscular dystrophy (BMD)[7], which are caused by total and partial loss of protein expression of the dystrophin gene, respectively[7]. DMD accounts for about half all DM cases[8]. DMD is X-linked and thus occurs only in males[9].

Muscle disease in DMD-carriers varies significantly in clinical presentation, from creatine-kinase (CK)-elevation only[10], exercise intolerance[11], to blatant muscle weakness and wasting[11]. Cardiac disease also varies significantly across individual DMD-carriers, and may include ECG abnormalities (including a wide variety of rhythm and voltage abnormalities, including sinus tachycardia, short PR intervals, and deep and narrow Q waves)[12], systolic dysfunction, heart failure and myocardial fibrosis[13]. In the index case, the patient presented with dilated cardiomyopathy. This feature has been reported previously, but only as a scattered case report. The clinical course of cardiovascular impairment in patients with DMD could be summarized in three cardinal phases[9]: a preclinical phase of the disease when patients have no symptoms of heart failure and cardiac investigations reveal no specific findings; a transition phase with apparent symptoms and detectable signs of cardiac impairment but compensated heart function; and a final phase of end-stage cardiomyopathy and death.

There is no cure for DMD. The goal of clinical management is to control heart failure. Glucocorticosteroids have been used to treat DMD though its effective needs further research[14]. Gene therapy that corrects calcium handling defects has produced promising results in experimental models of DCM, but clinical use remains out of sight[15].


DMD tends to manifest as weakness of skeletal muscles in early childhood, and involves the heart in the form of dilated cardiomyopathy later in early adulthood. There is no cure for DMD, and the goal of treatment is to maintain cardiac function.

Declaration of patient consent

The authors certify that they have obtained all the appropriate patient consent forms. The consent included using their data for analysis as well as images for illustration purpose on the condition that any information that could potentially reveal patient identity is concealed.

Conflict of interest statement

The authors declare that they have no financial conflict of interest with regard to the content of this report.


[1]. Mcnally EM, Kaltman JR, Benson DW, et al. Contemporary cardiac issues in Duchenne muscular dystrophy. Working Group of the National Heart, Lung, and Blood Institute in collaboration with Parent Project Muscular Dystrophy. Circulation 2015;131:1590–1598. doi:10.1161/CIRCULATIONAHA.114.015151.
[2]. Ling C, Dai Y, Fang L, et al. Exonic rearrangements in DMD in Chinese Han individuals affected with Duchenne and Becker muscular dystrophies. Hum Mutat 2020;41:668–677. doi:10.1002/humu.23953.
[3]. Romitti PA, Zhu Y, Puzhankara S, et al. Prevalence of Duchenne and Becker muscular dystrophies in the United States. Pediatrics 2015;135:513–521. doi:10.1542/peds.2014-2044.
[4]. van Westering TL, Betts CA, Wood MJ. Current understanding of molecular pathology and treatment of cardiomyopathy in duchenne muscular dystrophy. Molecules 2015;20:8823–8855. doi:10.3390/molecules20058823.
[5]. Duan D, Rafael-Fortney JA, Blain A, et al. Standard Operating Procedures (SOPs) for Evaluating the Heart in Preclinical Studies of Duchenne Muscular Dystrophy. J Cardiovasc Transl Res 2016;9:85–86. doi:10.1007/s12265-015-9669-6.
[6]. Jelinkova S, Vilotic A, Pribyl J, et al. DMD Pluripotent Stem Cell Derived Cardiac Cells Recapitulate in vitro Human Cardiac Pathophysiology. Front Bioeng Biotechnol 2020;8:535. doi:10.3389/fbioe.2020.00535.
[7]. Mercuri E, Bonnemann CG, Muntoni F. Muscular dystrophies. Lancet 2019;394:2025–2038. doi:10.1016/S0140-6736(19)32910-1.
[8]. Huang M, Magni N, Rice D. The prevalence, characteristics and impact of chronic pain in people with muscular dystrophies: a systematic review and meta-analysis. J Pain 2021;22:1343–1359. doi:10.1016/j.jpain.2021.04.001.
[9]. D’Amario D, Gowran A, Canonico F, et al. Dystrophin cardiomyopathies: clinical management, molecular pathogenesis and evolution towards precision medicine. J Clin Med 2018;7. doi:10.3390/jcm7090291.
[10]. Kamdar F, Garry DJ. Dystrophin-deficient cardiomyopathy. J Am Coll Cardiol 2016;67:2533–2546. doi:10.1016/j.jacc.2016.02.081.
[11]. Soltanzadeh P, Friez MJ, Dunn D, et al. Clinical and genetic characterization of manifesting carriers of DMD mutations. Neuromuscul Disord 2010;20:499–504. doi:10.1016/j.nmd.2010.05.010.
[12]. James J, Kinnett K, Wang Y, et al. Electrocardiographic abnormalities in very young Duchenne muscular dystrophy patients precede the onset of cardiac dysfunction. Neuromuscul Disord 2011;21:462–467. doi:10.1016/j.nmd.2011.04.005.
[13]. Villa C, Auerbach SR, Bansal N, et al. Current practices in treating cardiomyopathy and heart failure in duchenne muscular dystrophy (DMD): understanding care practices in order to optimize DMD heart failure through ACTION. Pediatr Cardiol 2022;1–9. doi:10.1007/s00246-021-02807-7.
[14]. Raman SV, Cripe LH. Glucocorticoid therapy for Duchenne cardiomyopathy: a Hobson's choice? J Am Heart Assoc 2015;4. doi:10.1161/JAHA.115.001896.
[15]. Adorisio R, Mencarelli E, Cantarutti N, et al. Duchenne dilated cardiomyopathy: cardiac management from prevention to advanced cardiovascular therapies. J Clin Med 2020;9. doi:10.3390/jcm9103186.

Duchenne muscular dystrophy; Dilated cardiomyopathy

Copyright © 2022 China Heart House.