Duchenne Muscular Dystrophy: Causes, Symptoms and Pathophysiology

Running head: PHARMACOLOGY
Pharmacology Assignment:
Duchenne Muscular Dystrophy
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1PHARMACOLOGY
Duchenne Muscular Dystrophy
Introduction:
Muscular dystrophy is a group of diseases that leads to degeneration, loss and
weakness of the muscles and muscle mass and is mainly caused due to genetic causes.
Duchenne Muscular Dystrophy (DMD) is a specific type of muscular dystrophy that occurs
predominantly among male. This is a genetic disorder that leads to an absence of the
cytoplasmic protein called dystrophin in muscle fibers thereby leading to the clinical
outcomes typical to the disease (Long et al. 2016; Li et al. 2015).
Description of the condition:
DMD is a progressive type of muscular dystrophy that is mainly diagnosed among
male, however females can also be affected in rare cases. The disease can occur at all ages,
however the symptoms becomes the most noticeable by the age of four. The disease leads to
the atrophy, loss and weakness of the cardiac and skeletal muscles thereby affecting their
function (Emery et al. 2015). The early symptoms of the disease can include a slower
movements while walking, sitting or standing or difficulties in speech. The atrophy and
muscular weakness usually starts with the musculature associated with the pelvis, hips,
shoulders and upper legs and can also cause an enlargement of the calves. Children afflicted
with this condition may show difficulties or abnormal gait while walking, running, climbing
stairs and while sitting down and getting up (Yiu and Kornberg 2015). The condition can also
impact memory and the ability of communicate. With progression of age, the condition
spreads to the trunk, arms and legs and a wheelchair is usually needed for movement.
Weakness of the muscle also leads to the cardiac and respiratory conditions (Angelini 2018).

2PHARMACOLOGY
The condition is caused due to mutations in the DMD gene which codes for a specific
protein known as dystrophin (Ousterout et al. 2015). This is a cytoplasmic protein (present in
muscle fiber cells) which forms a protein complex (called the dystrophin associated protein
complex) that functions in the interconnection of the cytoskeleton of the cell to the
extracellular matrix. This allows dystrophin to maintain the strength of the muscle fibers
(Aartsma-Rus et al. 2016). The mutation of the DMD gene leads to the production of
inadequate amount of dystrophin leading to the atrophy of the muscle fibers. The gene is
linked to the X chromosome and is a recessive gene and therefore is usually inherited from a
family member. However the DMD can also occur spontaneously, without any family history
of the disease. The disease does not have any known cure, however treatments are available
that can be used to manage the symptoms of the condition (Long et al. 2016; Li et al. 2015).
How the reduction or absence of dystrophin ultimately leads to the clinical symptoms:
One of the key functions of dystrophin is to provide strength and support to the
muscle fibers by allowing it to attach the cytoskeleton of the fiber cells to its extracellular
matrix by forming protein complexes called the Dystrophin Associated Protein Complex
(DAPC). Reduction in this protein inside the muscle fiber cells causes the reduction of the
stiffness of the cell, increases the deformability of the sarcolemma (the tubular sheath that
covers the muscle fibers) as well as reduces the mechanical stability of the structural
component of the muscle called the costameres and its connections to the myofibrils nearby.
This can lead to the weakening of the muscles, reduction in the muscular mass and muscular
atrophy. The DAPC also helps to scaffold different signaling and channel proteins and has
functions in the process of regulating cell signals. Reduction in dystrophin thus affects the
process of cell signaling which further increases the risks of muscular atrophy and weakness
(Dial et al. 2018; Constantin 2014).