Muscular dystrophies

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Dpt. Aamir Memon
Muscular Dystrophy

2. Muscular Dystrophies Tables
Muscular dystrophy (MD) is a group of inherited diseases in which the muscles that control
movement (called voluntary muscles) progressively weaken. In some forms of this disease,
the heart and other organs are also affected.
Type Age at onset Symptoms, rate of progression,
and life expectancy
Becker adolescence to early
adulthood
Symptoms are almost identical to
Duchenne, but less severe; progresses
more slowly than Duchenne; survival into
middle age.
Congenital birth Symptoms include general muscle
weakness and possible joint deformities;
disease progresses slowly; shortened life
span.
Duchenne 2 to 6 years Symptoms include general muscle
weakness and wasting; affects pelvis,
upper arms, and upper legs; eventually
involves all voluntary muscles; survival
beyond 20s is rare.
Distal 40 to 60 years Symptoms include weakness and wasting
of muscles of the hands, forearms, and
lower legs; progression is slow; rarely
leads to total incapacity.
Emery-Dreifuss childhood to early
teens
Symptoms include weakness and wasting
of shoulder, upper arm, and shin muscles;
joint deformities are common; progression
is slow; sudden death may occur from
cardiac problems.
Facioscapulohumeral childhood to early
adults
Symptoms include facial muscle
weakness and weakness with some
wasting of shoulders and upper arms;
progression is slow with periods of rapid
deterioration; life span may be many
decades after onset.
Limb-Girdle late childhood to
middle age
Symptoms include weakness and wasting,
affecting shoulder girdle and pelvic girdle
first; progression is slow; death is usually
due to cardiopulmonary complications.
Myotonic 20 to 40 years Symptoms include weakness of all muscle
groups accompanied by delayed
relaxation of muscles after contraction;
affects face, feet, hands, and neck first;
progression is slow, sometimes spanning
50 to 60 years.
Oculopharyngeal 40 to 70 years Symptoms affect muscles of eyelids and
throat causing weakening of throat
muscles, which, in time, causes inability

3. to swallow and emaciation from lack of
food; progression is slow.
Muscular dystrophies are of nine types but more importantly include:
 X-linked inheritance: Duchenne and Becker
 Autosomal recessive: Limb girdle
 Autosomal dominant: Fascioscapulohumeral and oculopharyngeal
1. Becker MD (BMD)
Age of onset
 Occurs at 2 to 16 years but can appear as late as age 25
 Becker muscular dystrophy affects only males (1 in 30,000)
Cause
 Mutations in dystrophin gene resulting in decreased amount of dystrophin, usually of
abnormal molecular weight
Symptoms
 Generalized weakness and wasting first affecting the muscles of the hips, pelvic area,
thighs and shoulders.
 Calves are often enlarged (pseudohypertrophy).
 BMD is similar to Duchenne MD but often much less severe.
 There can be significant heart involvement.
 Usually, patients affected by Becker's MD are able to walk until at least age 15, and
often well into their twenties and thirties.
 Serum CK (creatinine kinase) levels decline as muscle tissue is progressively
replaced by fat and fibrous tissue.
Rate of Progression
 Disease progresses slowly and with variability but can affect all voluntary muscles.
 Slower than Duchenne MD
Expected Lifespan
 Well into middle age.
 Most with BMD survive well into mid- to late adulthood.
Inheritance
 X-linked recessive.
 BMD primarily affects boys and men, who inherit the disease through their mothers.
 Women can be carriers but usually exhibit no symptoms-, because the dystrophin
gene is located on the X chromosome - of which women have 2 copies - and one

4. functioning copy of the dystrophin gene is generally sufficient for normal muscle
function.
2. Congenital MD (CMD)
 The two forms that have been identified -- Fukuyama and congenital muscular
dystrophy
Age of onset
 Already present at or near birth
 affect males and females
Cause
 Genetic mutations affecting some of the proteins (especially myosin deficiency)
necessary for muscles and sometimes for the eyes and or brain.
Symptoms
 General muscle weakness and possible joint stiffness or deformities.
 Depending on the type, it may involve scoliosis (spinal curvature), respiratory
problems, mental retardation or learning disabilities, eye defects or seizures
 Severe and early contractures (shortening or shrinking of muscles resulting into joint
problems)
 Fukuyama congenital muscular dystrophy causes abnormalities in the brain and often
seizures
Rate of Progression
 Slow
Expected Lifespan
 Varies, but is generally a bit shorter than normal people
Inheritance:
 Autosomal recessive or autosomal dominant; these diseases are sometimes inherited
through both parents and sometimes inherited from one parent. They can also occur
spontaneously because of a newly developed genetic flaw (mutation)
3. Duchenne Muscular Dystrophy
 It is most common in young males and is the most common form of dystrophinopathy
in children

5. Age of onset
 2 to 6 years (Early childhood)
 affects only males; females are carriers.
Cause
 An absence of dystrophin (Abnormalities in a gene encoding dystrophin--located in
the Xp21 region), a protein that helps keep muscle cells intact.
 Deletion (most common), point mutation also seen.
 Dystrophin and dystrophin-associated protein complex anchors actin to membrane
glycoprotein; absence of dystrophin causes transfer of the force of contraction to
connective tissue and myocyte degeneration
Symptoms
 General and severe muscle weakness and wasting, beginning from the upper arms,
hips, pelvic area, thighs and shoulders
 Weakness begins in the pelvic girdle muscles, and then shoulder girdle is affected
which manifests by 5 years.
 Weakness eventually progresses to all voluntary muscles.
 Characterized by a positive Gowers’ maneuver (requiring the assistance of upper
extremities to stand up) and pseudohypertrophy (enlargement of calf muscles with
weakness).
 In most cases, the arms, legs, and spine become progressively deformed,
 May be associated with intellectual impairment or cognitive impairment.
 Severe breathing and heart problems causing (arrhythmias and heart failure) mark the
later stages of the disease.
 Disease progression varies, but many people with Duchenne (1 in 3,500 boys) need a
wheelchair by the age of 12.
 Serum CK (creatinine kinase) levels decline as muscle tissue is progressively replaced
by fat and fibrous tissue.
Rate of Progression
 Fast
 DMD eventually affects all voluntary muscles, and the heart and breathing muscles
Expected Lifespan
 Survival is rare beyond the early 30s (as much as 25 years, survival past the twenties
is very rare).
 Those with Duchenne MD usually die in their late teens or early 20s.
 Paralysis and death by second to third decade.
 Death results from respiratory insufficiency, pulmonary infection, and cardiac failure.
Inheritance
 X-linked recessive.

6.  DMD primarily affects boys, who inherit the disease through their mothers.
 Women can be carriers of DMD but usually exhibit no symptoms.
4. Distal MD (DD)
Cause
 A mutation in any of at least eight genes that affect proteins necessary to the function
of muscles.
Age of Onset
 40 to 60 years
Symptoms
 Weakness and wasting of distal muscles (those farthest from the center) of the
forearms, hands, lower legs, and feet.
 affects fewer muscles than other forms of muscular dystrophy
Rate of Progression
 Slow progression;
 not life-threatening.
Expected Lifespan
 Rarely leads to life-threatening situations
Inheritance
 May be autosomal dominant (a faulty gene is inherited from one parent), or autosomal
recessive (a faulty gene is inherited from each parent).
5. Emery-Dreifuss Muscular Dystrophy
Age of onset
 Usually by 10 years of age
 affects only males
Cause
 Mutations in the genes that produce emerin, lamin A or lamin C, proteins in the
membrane that surrounds the nucleus of each muscle cell.

7. Symptoms
 Weakness and wasting of shoulder, upper arm and calf muscles;
 Muscle shortening (contractures) occurs early in the disease
 Often causes joint stiffening or deformities; fainting (because of cardiac
abnormalities).
 Life-threatening heart problems are common and can also affect carriers
Rate of Progression
 Disease usually progresses slowly of all
 Cardiac complications are common and sometimes require a pacemaker.
Expected Lifespan
 Due to this disease affecting cardiac muscle fibers, sudden death is possible because
of cardiac complications
Inheritance
 Can be X-linked recessive, primarily affecting males, who inherit the disease through
their mothers.
 Another type is autosomal dominant, meaning it can be inherited through either
parent; an autosomal recessive type occurs when a faulty gene is inherited from each
parent.
6. Facioscapulohumeral MD (FSHD)
Age of onset
 Usually by age 20.
 affects males and females
Cause
 A missing piece of DNA on chromosome 4.
Symptoms
 Weakness and wasting of the muscles around the eyes and mouth, and of the
shoulders, upper arms and lower legs initially, with later weakness of abdominal
muscles and sometimes hip muscles.
 Walking, chewing, swallowing, and speaking problems can occur.

8.  About 50% of of those with facioscapulohumeral MD can walk throughout their
lives, and most live a normal life span.
Rate of Progression
 Slow and not steady, interspersed with periods of rapid worsening/ deterioration
Expected Lifespan
 Disease may span usually many decades after onset
Inheritance
 Autosomal dominant; the disease may be inherited through either the father or the
mother, or it may occur without a family history.
7. Limb-Girdle MD (LGMD)
Age of onset
 late childhood to middle age
 affects males and females
Cause
 A mutation in any of at least 15 different genes that affect proteins necessary for
muscle function.
Symptoms
 Muscle wasting and weakness, beginning from the shoulder girdle and pelvic girdle
 Within 20 years, walking becomes difficult or impossible
Rate of Progression
 Usually progresses slowly, with cardiopulmonary complications sometimes occurring
in later stages of the disease.
Expected Lifespan
 Varies, death is usually due to cardiac or respiratory complication.
 Sufferers typically live to middle age to late adulthood.
Inheritance
 Some types are autosomal dominant, meaning LGMD is inherited from one parent.
 Other types are autosomal recessive and occur when a faulty gene is inherited from
each parent.

9. 8. Myotonic (also called MMD or Steinert's disease)
 The most common form of muscular dystrophy in adults.
Age of onset
 Occurs at any age, but usually 20 to 40 years {although it can be present at birth in
Type 1 congenital myotonic dystrophy (congenital MMD)}
 Affects both men and women.
Cause
 A repeated section of DNA on either chromosome 19 or chromosome 3.
Symptoms
 Generalized weakness and muscle wasting first affecting the face, lower legs,
forearms, hands and neck.
 Myotonia/delayed relaxation of muscles (difficulty or total incapacity of relaxing a
muscle at will after a contraction resulting into prolonged spasm or stiffening of
muscles after use. This symptom is usually worse in cold temperatures)
 The disease causes muscle weakness and also affects the central nervous system,
heart, gastrointestinal tract, eyes, respiration, and hormone-producing glands
 Learning disabilities occur in some cases.
 Congenital myotonic dystrophy is the more severe form.
Rate of Progression
 Slow
Expected Lifespan
 Varies a lot, but can be as much as 50 to 60 years
Inheritance
 Autosomal dominant; the disease may be inherited through either the father or the
mother.
9. Oculopharyngeal Muscular Dystrophy
Age of onset
 40 to 70 years
 in men and women

10. Cause
 A faulty gene for poly(A)-binding protein nuclear 1 (PABPN1), which is suspected to
lead to production of extra chemical material that causes formation of clumps in the
muscle cells.
Symptoms
 OPMD first causes weakness of the muscles of the eyelids and throat; weakness of
facial and limb muscles often occurs later.
 Weakness in the muscles of the eye (drooping eyelids) and of the throat
(accompanied generally by an inability to swallow, causing possible nutritional
deficiencies and emaciation
 Weakness in pelvic and shoulder muscles may occur later.
 Choking and recurrent pneumonia may occur.
Rate of Progression
 Slow
Expected Lifespan
 Varies
Inheritance
 May be autosomal dominant (a faulty gene is inherited from one parent), or
 autosomal recessive (a faulty gene is inherited from each parent).
Diagnosis of MDs
 A careful diagnosis also involves careful medical history and a thorough physical
exam to determine the distribution of symptoms and to rule out other causes.
 Family history is very important, since all the muscular dystrophies are genetic - and
usually inherited - conditions (though rarely there will be new mutations which are
not detectable with family history).
 EMG are also useful: they stimulate muscles using electrical shocks and the reaction
is abnormal in individuals with muscular dystrophy.
 Muscle biopsies are among the most reliable tests: they consist of taking a small piece
of muscle and examining it with a microscope (fibers affected by MD are unusually
large and interspersed with dead cells).
 The golden standard for MD diagnosis, however, is a DNA test: in the past, these tests
were performed on blood samples and allowed diagnosis by identifying a specific
mutation of the dystrophin gene.

11.  There is now a new DNA test, called single condition amplification/internal primer
(SCAIP) sequencing, which allows doctors to have a much more accurate picture of
the entire dystrophin gene, so they can find multiple variations, providing more than
just one type of diagnosis.
 In the next years this test should become more widely available to the general public
 In any case, the two most reliable tests to diagnose a muscular dystrophy are a muscle
biopsy or a DNA test (even if usually a blood test is sufficient)
 The usual procedure is to first look for physical signs, then use a blood test. Blood
tests work by determining the level of creatine phosphokinase (CPK): in children with
the condition, these levels are usually 5 to 10 times greater than the maximum level
found in normal individuals, but they can get as high as 100 times