C h a p t e r 3 6
Disorders of Neuromuscular Function
889
Skeletal Muscle Disorders
Muscle Atrophy
Maintenance of muscle strength requires relatively fre-
quent movements against resistance. Reduced use results
in muscle atrophy, which is characterized by a reduction
in the diameter of the muscle fibers because of a loss of
protein filaments.
8
When a normally innervated muscle
is not used for long periods, the muscle cells shrink in
diameter, and although the muscle cells do not die, they
lose much of their contractile proteins and become weak-
ened. This is called
disuse atrophy,
and it occurs with
conditions such as immobilization and chronic illness.
The most extreme examples of muscle atrophy are found
in persons with disorders that deprive muscles of their
LMN innervation. This is called
denervation atrophy.
Muscular Dystrophy
Muscular dystrophy
is a term applied to a number of
genetic disorders that produce progressive degenera-
tion and necrosis of skeletal muscle fibers and eventual
replacement with fat and connective tissue.
9–11
They are
primary diseases of muscle tissue and probably do not
involve the nervous system. As the muscle undergoes
necrosis, fat and connective tissue replace the muscle
fibers, which increases muscle size and results in muscle
weakness. The increase in muscle size resulting from
connective tissue infiltration is called
pseudohypertro-
phy.
Muscle weakness is insidious in onset but continu-
ally progressive, varying with the type of disorder.
The two most common forms of muscular dystrophy
are Duchenne muscular dystrophy (DMD) and Becker
muscular dystrophy (BMD), both of which are inher-
ited as an X-linked recessive trait. Duchenne muscular
dystrophy is the most common and severe form, with an
incidence of 1 in every 3600 to 6000 live male births.
11
Despite the X-linked inheritance in DMD, about 30%
of cases are due to new mutations and the mother is not
a carrier.
10
Female carriers are usually asymptomatic.
Affected girls are occasionally encountered, but usually
have much milder symptoms than boys. Becker muscular
dystrophy, which shares the same genetic locus as DMD,
manifests later in childhood or adolescence and has a
slower and less severe course of progression.
Both DMD and BMD are caused by mutations in
the dystrophin gene, located on the short arm of the
X chromosome. Dystrophin is a large protein that is
expressed in a variety of tissues, including all types of
muscle cells.
8–11
It attaches portions of the muscle sarco-
mere to the cell membrane, maintaining the structural
integrity of skeletal and cardiac muscle cells. The role
of dystrophin in transferring the force of contraction
to the extracellular connective tissue matrix has been
proposed as the basis for muscle cell degeneration that
occurs with dystrophin defects or changes in other pro-
teins that interact with dystrophin. The dystrophin gene
is one of the largest in the human genome, spanning
2.3 million base pairs, a factor that is thought to make
it particularly vulnerable to mutations. Muscle biopsy
specimens from individuals with DMD show little or no
dystrophin. In comparison, those with BMD, who also
have mutations in the dystrophin gene, show diminished
amounts of dystrophin, usually of an abnormal molecu-
lar weight, reflecting mutations that allow synthesis of
an abnormal protein of smaller size.
8
Clinical Course.
Boys with DMD are usually asymptom-
atic at birth and during infancy.
8–11
Early gross movements
such as rolling, sitting, and standing are usually achieved at
the proper age. The postural muscles of the hips and shoul-
ders are usually the first to be affected. Pseudohypertrophy
of the calf muscle eventually develops (Fig. 36-5). Signs
of muscle weakness usually become evident beginning
at 2 to 3 years of age, when the child begins to fall fre-
quently. Imbalances between agonist and antagonist mus-
cles lead to abnormal postures and the development of
contractures and joint immobility. Scoliosis (curvature of
the spine) is common. Wheelchairs usually are needed at
approximately 7 to 12 years of age.
10
Function of the dis-
tal muscles usually is preserved well enough that the child
can continue to use eating utensils and a computer key-
board. The function of the extraocular muscles also is well
preserved, as is the function of the muscles controlling uri-
nation and defecation. Incontinence is an uncommon and
late event. Respiratory muscle involvement results in weak
and ineffective cough, frequent respiratory infections, and
decreasing respiratory reserve.
Cardiomyopathy is a common feature of the disease.
The severity of cardiac involvement, however, does not
necessarily correlate with skeletal muscle weakness.
Some persons die early as the result of severe cardio-
myopathy, whereas others maintain adequate cardiac
function until the terminal stages of the disease. Death
from respiratory and cardiac muscle involvement usu-
ally occurs in young adulthood.
Diagnosis and Treatment.
Observation of the child’s
voluntary movement and a complete family history pro-
vide important diagnostic data for the disease. Serum
levels of the enzyme creatine kinase (CK), which leaks
out of damaged muscle fibers, suggests the presence of
FIGURE 36-5.
Pseudohypertrophy of the calves exercise for
a child with proximal muscle weakness caused by Duchenne
muscular dystrophy.
