Discussion:
Becker muscular dystrophy is one of the two common forms of Duchenne muscular dystrophy, which is a X-linked recessive genetic disease. It usually occurs in male, while female are the carriers of the abnormal chromosome.
According to the difference of onset age and disease course, patients with dystrophinopathy are divided into Duchenne´s muscular dystrophy (DMD) and Becker’s muscular dystrophy (BMD), both of which are caused by the encoding gene absence and partially-absence of dystrophin (1).
The involved gene is located in the XP21.2 region of sex chromosome, and is the largest gene known to human at present. It is about 2.4Mb in length, contains 79 exons and 79 introns, and encodes mRNA about 14KB. The translated product is anti-dystrophin, which is located in the lipid of muscle cell membrane, and which plays an important role in stabilizing cell membrane and preventing cell necrosis and autolysis. The main types of gene absence include exon deletion, duplication and gene micromutation (2, 3).
The main manifestations of Duchenne muscular dystrophy (DMD/BMD) in the early stage are atrophy and weakness of the proximal lower extremities muscular and pelvic girdle, pseudohypertrophy of calf gastrocnemius, duck step and Gowers sign. In the late disease stage, systemic skeletal muscle atrophy, myocardial involvement, featured by myocardial fibrosis and adipose tissue infiltration might occur. The myocardial involvement is usually resulted from the absence of myocardial dystrophy protein. The atrophy degeneration, fibrosis and infiltration of adipose tissue of the left ventricular myocardium could lead to abnormal ventricular wall motion, and eventually dilated cardiomyopathy and severe arrhythmias.
Clinically, disease course of DMD patients is progressive and the prognosis is poor. About 1/3 of the patients might suffer from mental retardation and usually die of respiratory or heart failure in their 20s. BMD is an allelic disease, which is relatively rare and patients usually present with the general characteristics of Duchenne muscular dystrophy. However, the disease progress of BMD is relatively slow, the average age of disease onset is late and survival outcome is better than DMD, cognitive impairment is usually absent in BMD patients.
In our case, disease onset of the disease is late, clinical manifestations are typical for Duchenne muscular dystrophy, combined with typical changes on serum enzymology, electromyography, pathology and genetics. He was first diagnosed as “pseudo hypertrophic muscular dystrophy”. Then, based on the late onset and slow progression disease feature and absence of cognitive impairment, patient was diagnosed as Becker muscular dystrophy (BMD). In addition, echocardiography examination indicated whole heart enlargement with reduced LVEF, and CMR indicated myogenic injury, so the diagnosis of DCM was established, which might be secondary to BMD.
The most common cause of death in BMD is DCM and associated heart failure (4). The patient reported here did suffer from severe heart failure and our patient presented typical signs and symptoms of DCM-related heart failure with NYHA classification III-IV. It is of importance to define the disease feature and cardiac structural and function changes with the help of echocardiography, magnetic resonance imaging and other methods in BMD patients with or without symptoms of heart failure and monitor related changes thereafter (5).
At present, there is no effective radical treatment for Duchenne muscular dystrophy . Genetic counseling and prenatal diagnosis for high-risk pregnant women with related family history are recommended in some countries. Multidisciplinary management of DMD/BMD patients is of importance aiming to slow down disease progression, and improve quality of life and outcome. Glucocorticoid is the only proved drug by evidence-based medicine to delay the clinical course of DMD (6), which can delay muscle strength decline, muscle contracture, joint deformation and heart damage. Clinicians should pay attention to potential adverse reactions related long-term glucocorticoid treatment in these patients. For BMD patients combined with cardiac damage and without heart failure symptoms, angiotensin converting enzyme inhibitors (ACEI) and β-blockers could delay progression of left ventricular dysfunction (7). Sodium-glucose transport protein 2 (SGLT2) inhibitors are new-comers for HF patients with preserved or reduced LVEF (ref), efforts should be made to observe if BMD patients with heart failure could benefit from this medication or not. Left ventricular assist device shows a certain application prospect in improving quality of life and survival in BMD patients (8). In addition, impact of other treatment methods, such as gene therapy, cell transplantation and heart transplantation therapy, is under exploration now.