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.