MUSCULAR DYSTROPHY

Muscular dystrophy refers to a group of genetically determined disorders characterized by progressive

degeneration of skeletal muscle without primary structural abnormality in the lower motor neuron.
These disorders have been classified on the basis of the clinical distribution and severity of muscle
weakness and by pattern of inheritance. The majority of muscular dystrophies are associated with
progressive muscle weakness and atrophy and elevated concentrations of serum creatine kinase (CK),
but these are not absolute findings. There are more than 30 different types of muscular dystrophy and
each affects certain muscles and varies in severity. Some types of muscular dystrophy affect children
while others don’t appear until adulthood.

The most common type, called Duchenne muscular dystrophy, usually begins between ages 2 to 5 and
symptoms progress quickly. About 50 percent of all people with muscular dystrophy have this type.
Duchenne muscular dystrophy most often affects boys, though girls can inherit the gene and pass it to
their children.

Some other types of muscular dystrophy that can affect children include:
 Becker: This type is related to Duchenne muscular dystrophy, but is less severe.
 Emery-Dreifuss: Most common in boys, this type of muscular dystrophy causes weakness and
progressive wasting of the lower leg and upper arm muscles.
 Facioscapulohumeral: can affect both boys and girls, and the symptoms usually first appear
during the teen years. It tends to progress slowly. Muscle weakness first develops in the face,
making it difficult for a child to close the eyes, whistle, or puff out the cheeks. The shoulder and
back muscles gradually become weak, and kids have trouble lifting objects or raising their hands
overhead. Over time, the legs and pelvic muscles also may lose strength.
 Limb-girdle: affects boys and girls equally. Symptoms usually start when kids are between 8 and
15 years old. This form progresses slowly, affecting the pelvic, shoulder, and back muscles. The
severity of muscle weakness varies — some kids have only mild weakness while others develop
severe disabilities and as adults need to use a wheelchair.
 Myotonic dystrophy: also known as Steinert's disease, is the most common adult form of MD,
although half of all cases are diagnosed in people under 20 years old. The main symptoms
include muscle weakness, myotonia (in which the muscles have trouble relaxing once they
contract), and muscle wasting (when the muscles shrink over time).
 Distal: Also called distal myopathy, is a less severe form of muscular dystrophy that usually
progresses slowly.
All types of muscular dystrophy get worse over time, and can eventually cause the inability to walk.
Some types of muscular dystrophy can also cause problems with breathing.

There is no cure for muscular dystrophy, but treatments can prevent complications and help with
symptoms.
SIGN AND SYMPTOMS
Although all types of muscular dystrophy are characterized by progressive skeletal muscle weakness, the
distribution of weakness and rate of progression differ for each disorder. Similarly, the prognosis varies
considerably for the different types of muscular dystrophy. In addition, the progressive skeletal changes
of most dystrophies (eg, joint contractures, scoliosis) are related to muscle weakness. In severe cases,
weakness of respiratory muscles leads to restrictive lung disease and eventual respiratory failure.

Symptoms can start anywhere between birth and middle age, depending on the type of MD. In young
babies, the muscle weakness may be noticed as floppiness. In older babies and young children, the
weakness may show up as a delay in learning to hold up their head, sit up, crawl or walk.

Other symptoms include:

 muscle wasting – your muscles become thin
 muscle hypertrophy – bulkier than normal muscles, even though they work less well
 aches or pains in your muscles
 contractures – tight joints, due to tightness of your muscles or reduced movement of your joints
 in some cases, symptoms of heart disease without much muscle weakness.

The most common symptom of all types of muscular dystrophy is muscle weakness that gets worse over
time.
Each type of muscular dystrophy has its own specific symptoms:
Duchenne
With the classic clinical presentation, affected boys are asymptomatic during early infancy and
have normal motor milestones. Less commonly, some boys present with global developmental delay or
delayed achievement of early motor milestones. At approximately 4 years of age, affected boys develop
a waddling gait and difficulty climbing stairs due to pelvic weakness. Toewalking results from tightness
of the Achilles tendon. These boys are unable to jump, and they fall frequently. The progressive difficulty
in arising from the floor because of proximal pelvic girdle weakness results in the Gower maneuver.
Rising from a supine position requires the child to assume a prone position, followed by extension of the
knees and elbows. He then lets go of one hand at a time, supporting it on the knee, and gradually
straightens into a standing position by “climbing up himself” with his hands.

Pseudohypertrophy of muscles, particularly pseudohypertrophy of the calf muscles, is common.

Pseudohypertrophic muscles feel rubbery and firmer than normal. Histologic examination shows
replacement of muscle fibers by fatty and fibrous tissue as well as some hypertrophy of remaining
muscle fibers. Weakness of hip extensors leads to compensatory lumbar lordosis to maintain an upright
posture (Fig. 1). Weakness of the arms (proximal more than distal) becomes apparent as the disease
progresses. The age at which the ability to walk is lost varies, but this occurs generally before 13 years in
Duchenne dystrophy. Following loss of ambulation, fixed skeletal deformities, such as equinovarus
deformities of the feet (Fig. 2) and scoliosis (Fig. 3), develop rapidly. Sphincter control usually is
unaffected, and there are no difficulties with chewing or swallowing. Weakness of intercostal muscles
leads to progressive restrictive respiratory defect with nocturnal hypoventilation in the late teens to
early 20s. Eventually respiratory failure occurs, at which time the option for assisted ventilation must be
addressed. Although electrocardiographic abnormalities are present in the early stages of the disease,
symptoms and signs of progressive cardiomyopathy develop only in the mid-teens. Most boys who have
Duchenne dystrophy die from cardiac or pulmonary problems in the late second or third decade.
 frequent falls
 having trouble getting up from a lying or sitting position
 a waddling walk
 difficulty running and jumping
 enlarged calf muscles

Duchenne dystrophy. Duchenne dystrophy.

Equinovarus foot deformities Progressive scoliosis
following loss of ambulation. following loss of ambulation.

Becker
Becker dystrophy results from deletions or mutations in the same gene as Duchenne dystrophy. It
has a similar clinical appearance and distribution of weakness, albeit milder in severity and with slower
deterioration (Fig. ). Some individuals may present with severe cramps on exertion. The onset of
symptoms often is later in childhood, and affected individuals remain ambulatory beyond 16 years of
age. Cardiac involvement may be severe and disproportionate to the skeletal muscle weakness. Clinically
apparent cardiomyopathy is present in approximately 15% of patients younger than 16 years of age and
in 75% of those older than 40 years. Affected individuals may survive into late adulthood.
 walking on tiptoes
 frequent falls
 muscle cramping
 later onset of symptoms than Duchenne
 Distal
 trouble with hand movements and extending the fingers
 difficulty climbing stairs and walking
 inability to stand on the heels or hop
Becker dystrophy. Note
prominence of calf muscles.

Congenital Muscular Dystrophy

Affected infants present with hypotonia and weakness at birth. There may be joint contractures of
variable severity and respiratory and swallowing difficulties. Some types of congenital muscular
dystrophy (eg, Fukuyama type, muscle-eye-brain disease, Walker-Warburg syndrome) are characterized
by intellectual retardation, seizures, hydrocephalus, and evidence of structural brain abnormalities or
ocular abnormalities. Children who have “pure” congenital muscular dystrophy often have a relatively
static, nonprogressive course in contrast to those who have central nervous system involvement and
exhibit progressive deterioration.

Facioscapulohumeral
Early signs and symptoms, which begin in late childhood or early adolescence, include facial weakness
and weakness of scapulohumeral muscles with preservation of deltoid strength (Fig.). Weakness of the
pelvic girdle may result in a lordotic posture. There usually is no cardiac or intellectual involvement.
Some individuals develop retinal vasculopathy and sensorineural hearing loss.
 weakening of the muscles around the eyes and mouth
 slanted shoulders or shoulder blades that looked "winged"
 trouble speaking, swallowing, or chewing
 hearing problems
 a curve in the spine
 A. Facioscapulohumeral dystrophy in a 16-
year-old male. Note the facial weakness. B.
Upward riding of scapulae on abduction of
arms.

Limb-girdle
This rapidly progressive, autosomal recessive dystrophy, which is similar in severity to Duchenne
dystrophy, has been described particularly in families from North Africa. Other cases are milder, with
loss of ambulation between 20 and 30 years of age. To date, this group of disorders has not been
classified in detail.
 weakness around the hips that spreads to the legs, shoulders, and neck
 frequent falls
 a waddle when walking
 rigid spine

Myotonic dystrophy
Myotonic dystrophy has a variable presentation. The principal clinical features in older children and
adults are facial weakness, muscle myotonia, and more marked distal muscle weakness. Cardiac muscle
involvement in advanced disease manifests as conduction defects, with arrhythmias in approximately
50% of affected patients. Smooth muscle involvement results in dysphagia, constipation, urinary tract
symptoms, and cholecystitis. Other organ involvement includes cataracts and endocrine disturbances
(eg, diabetes, testicular atrophy, and menstrual irregularities). There may be intellectual impairment
that worsens over time.

Congenital myotonic dystrophy, which almost invariably is transmitted maternally, is associated with the
worst prognosis. Affected infants most commonly are hypotonic, requiring respiratory and nutritional
support. Respiratory insufficiency is a major cause of mortality in early infancy. Respiratory function may
improve gradually. Other clinical features include preterm birth, facial diplegia, feeding difficulties,
arthrogryposis, and cognitive abnormalities (Fig. 5). Clinical myotonia presents at a later age. Thus, if
congenital myotonic dystrophy is suspected, clinical myotonia should be investigated in the mother (eg,
the “handshake test”).
 an inability to relax muscles after contracting them
  having a long, thin face and neck
 trouble swallowing
 cataracts, drooping eyelids, and other vision problems
 drowsiness
 in infants, trouble swallowing or breathing, lack of reflexes, muscle weakness in the face, and
delayed motor skills

Congenital myotonic dystrophy. Note the

prematurity, hypotonia, facial weakness with
tent-shaped mouth, and cryptorchidism.

Physical Examination

 Generally, neck flexors, wrist extensors, quadriceps, tibialis anterior, biceps and triceps
muscles are affected more.
  Deep tendon reflexes, slowly diminish and ultimately disappear
 Calf muscle enlargement (pseudo hypertrophy) contractures of the iliotibial bands, hip
flexors, and heel cords
 Equinovarus deformity of ankle is universal
 Asymmetric weaking of the paraspinal muscles leads to kyphoscoliosis, which in turn further
compromises pulmonary and gastrointestinal function.

Phases of Duchenne muscular dystrophy

The child's motor milestones may be at the upper limits of normal, or they may be slightly delayed.
Some of the delays may be caused by inherent muscle weakness, but a component may stem from brain
involvement.

In addition to mental deficits, another milestone delay is the patient's age at ambulation. Children with
Duchenne MD usually do not begin to walk until about age 18 months or later. In the Dubowitz study,
74% of children with Duchenne MD manifested the disease by age 4 years. By age 5 years, awareness
increases as the disease is manifested in all affected children when they experience difficulty with
school-related activities (eg, getting to the bus, climbing stairs, reciprocal motions during activities).

The Gower sign is a classic physical examination finding in MD and results from weakness in the child's
proximal hip muscles. To get up from a sitting or supine position, the child must first become prone on
the elbows and knees. Next, the knees and elbows are extended to raise the body. Then, the hands and
feet are gradually brought together to move the body's center of gravity over the legs. At this point, the
child may release one hand at a time and support it on the knee as he or she crawls up their legs to
achieve an upright position.

Although the Gower sign is a classic finding in Duchenne MD, it is by no means pathognomonic; other
types of MD and disorders with proximal weakness may also cause this sign.

While still ambulatory, the child may have minimal deformities, including iliopsoas or tendo Achillis
tightness. Mild scoliosis may be present if the child has an asymmetrical stance. Upper-extremity
involvement rarely occurs in the beginning, although proximal arm muscle weakness may be evident on
manual strength testing. When upper-extremity involvement manifests in later stages of Duchenne MD,
it is symmetrical and, along with distal weakness, usually follows a rapid worsening of the child's
condition toward being wheelchair bound.

The second important phase in Duchenne MD is the loss of ambulation. This usually occurs between the
ages of 7 and 13 years, with some patients becoming wheelchair-bound by age 6 years. With early
initiation of steroid treatment, prolongation of ambulation potential has been well documented.
However, If children with MD are still ambulating well after the age of 13 years, the diagnosis of
Duchenne MD should be questioned, because these patients may have Becker MD, the milder form of
MD.

Most authors have recommended posterior spinal fusion at 20° when the vital capacity is at its best.
However, some reports showed that respiratory function after spinal fusion did not significantly differ.
The investigators concluded that respiratory failure resulted from muscle weakness and not the
mechanical bellows of the chest cage, as was previously assumed.

Duchenne MD is a terminal disease in which death usually occurs by the third decade of life (mostly
from cardiopulmonary compromise), despite steroid treatment. The most common inciting event is a
respiratory infection that progresses extremely rapidly despite its initial benign course. The resultant
respiratory failure can easily occur from the underlying progressive nocturnal hypoventilation and
hypoxia or from an acute cardiac insufficiency.

Other types of muscular dystrophy

Becker MD is similar to Duchenne MD, but because patients have some measure of functioning
dystrophin, the manifestations of Becker MD occur later and are more mild. Patients tend to live past
the fourth or fifth decades.

Emery-Dreifuss MD is an uncommon sex-linked dystrophy that presents with early contractures and
cardiomyopathy in affected patients; the typical presentation involves tendo Achillis contractures, elbow
flexion contractures, neck extension contractures, tightness of the lumbar paravertebral muscles, and
cardiac abnormalities. Death may occur in the fourth or fifth decade as a result of first-degree
atrioventricular (AV) block, a condition that is usually not present at the initial presentation of this
disease.

Autosomal dominant distal MD is a rare form of MD and tends to become apparent in those aged 30-40
years; it is more commonly found in Sweden than in any other country and can cause a mild weakness
that affects the arms before the legs.

Autosomal dominant facioscapulohumeral dystrophy causes facial and upper-extremity weakness, and
scapulothoracic motion is decreased, with winging of the scapula. This type of dystrophy can occur in
both sexes and appear at any age, although it is more common in late adolescence.

Autosomal dominant oculopharyngeal dystrophy appears in those aged 20-30 years. The pharyngeal
muscle involvement leads to dysarthria and dysphagia, which may necessitate palliative cricopharyngeal
myotomy. The ocular component comprises ptosis, which may not become obvious until the patient's
mid life.

None of the autosomal dominant conditions significantly affect longevity.

Diagnostic Test
Progressive clinical symptoms that include muscle weakness are the basis for diagnosing muscular
dystrophy. Laboratory investigations play a lesser role.

SERUM CREATINE PHOSPHOKINASE (CK)

The normal range of CK varies between laboratories. At our center, a CK level below 365 U/L is
considered to be normal. It is important not to depend on a single CK level for important decisions, but
always to repeat the test on separate occasions. Elevated levels of this enzyme may indicate a significant
amount of skeletal or cardiac muscle necrosis. In Duchenne/Becker dystrophy, levels as high as 50 to
100 times normal are common. Interestingly, levels of CK are highest in the early stages of
Duchenne/Becker dystrophy, when the patient is asymptomatic, and subsequently decline gradually
over time as muscle tissue is lost and disease progresses. In other types of muscular dystrophy or
myopathy, levels of CK vary and even may be normal.

CK levels may be moderately elevated in severe, chronic neurogenic disorders such as spinal muscular
atrophy. It is important to recognize that up to 10-fold elevations in CK may occur following normal
vaginal delivery or acute hypoxic-ischemic cerebral injury. Other common causes of elevated CK include
intramuscular injections, trauma to muscles, and recent vigorous exercise.

ASPARTATE AMINOTRANSFERASE (AST)

The quantity of this enzyme may be mildly elevated in muscular dystrophy. In fact, many patients who
have Duchenne/Becker dystrophy have had a liver biopsy performed for investigation of “unexplained”
elevation of AST.

CHEST RADIOGRAPHY
An enlarged cardiac silhouette suggests cardiomyopathy. Thin ribs may be a clue to neuromuscular
disease of prenatal onset.

ELECTROMYOGRAPHY (EMG)
EMG shows low-amplitude, short-duration polyphasic motor unit action potentials. Although this test
may identify a myopathic process, its results are relatively nonspecific, and it often is technically difficult
to perform, especially in the young infant. It has a minor role in the investigation of muscular dystrophy.

CARDIAC INVESTIGATIONS
Electrocardiography may demonstrate conduction defects or arrhythmias. Echocardiography may
document cardiomyopathy.

MUSCLE BIOPSY
This procedure may be performed as either an open, surgical biopsy or as a needle biopsy. Characteristic
features of muscular dystrophy include muscle degeneration and regeneration and proliferation of
connective tissue. During the early stages of a disorder, or in milder types of muscular dystrophy (eg,
facioscapulohumeral dystrophy), changes may be minimal. Specialized immunocytochemical techniques,
such as staining for dystrophin, have greatly improved the specificity of this study.
 Muscle biopsy of a boy who has Duchenne dystrophy (hematoxylin and eosin stain). Note
variation in muscle fiber size, central nuclei, and increased lipid and connective tissue.

MOLECULAR GENETIC TECHNIQUES

Identification of specific gene deletions or DNA triplet repeat amplifications are rapidly becoming the
techniques of choice for confirming the diagnosis of common types of muscular dystrophy (eg,
Duchenne muscular dystrophy, myotonic dystrophy). For example, demonstration of a deletion within
the Xp21 gene on DNA blood screening has made invasive muscle biopsy unnecessary in approximately
two thirds of cases of Duchenne/Becker dystrophy. Similar genetic techniques are invaluable for
identifying carrier status and establishing prenatal diagnosis.
 REFERENCE
Muscular Dystrophy
 https://pedsinreview.aappublications.org/content/21/7/233
 https://kidshealth.org/en/parents/muscular-dystrophy.html
 https://www.healthnavigator.org.nz/health-a-z/m/muscular-dystrophy/
 https://www.slideshare.net/ManojPrabhakar61/muscular-dystrophies-71549418
 https://emedicine.medscape.com/article/1259041-clinical