Transcript Duchenne Muscular Dystrophyx

Duchenne
Muscular Dystrophy
BRIAN CHANDA CHILUBA
Dip.PT; Cert. NDT
NEUROLOGY CLASS PRESENTATION
Overview
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Basic information about Duchenne
muscular dystrophy
Inheritance
Prevalence
Symptoms
Treatments
What Is Duchenne Muscular
Dystrophy?(1)
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Genetic
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Progressive muscle weakness
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Defects in muscle proteins
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Death of muscle tissue
MUSCULAR DYSTROPHY
Muscular dystrophies - group of genetic conditions
characterized by progressive muscle weakness and wasting
(atrophy)
20 different types of muscular dystrophy exist
(DMD) is named after the French neurologist Guillaume
Benjamin Amand Duchenne (1806–1875), who first described the
disease in 1861
DMD
(DMD) is a severe recessive X-linked form of muscular
dystrophy characterized by rapid progression of muscle
degeneration, eventually leading to loss of ambulation and
death
DMD is caused by a defective gene for dystrophin (a protein
in the muscles) or by mutations in the dystrophin gene, which is
located on the X chromosome
DMD
DMD
absence
of
the
dystrophin
protein
weakens
the
connections between all of the proteins in the muscle and the cell
membrane
cell membrane becomes weaker and ruptures
particles, such as calcium, can move in and out of the ruptured
cell membrane
Where is This Gene?
PHYSIOLOGY OF
DYSTROPHIN
The dystrophin molecule anchors
the cytoskeleton of muscle cells to
the extracellular matrix, via the
dystrophin glycoprotein complex.
This includes the sarcoglycans
(mutations in which cause limbgirdle muscular dystrophies) and
dystroglycans.
Muscle cells that lack dystrophin
are mechanically fragile, and fail
after a few years, hence
progressive muscle weakness.
Duchenne Muscular Dystrophy
Inheritance(1)
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Mother carries the recessive gene and
passes it to her child
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Trait is usually expressed in
males only
Prevalence of DMD(1)
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Affects one in 3500
to 5000 newborn
males
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1/3 of these with
previous family
history
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2/3 sporadic
Symptoms of DMD(1)
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Symptoms usually appear before age 6
Delayed developmental milestones
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Loss of motor skills
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Characteristic gait
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Calf hypertrophy
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Clumsiness/frequent falls
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More Symptoms of DMD(1)
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Muscle weakness
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Difficulty climbing stairs or hills
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Difficulty rising (Gower’s sign)
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Difficulty walking/running
GOWERS SIGN
PROGNOSIS
Duchenne muscular dystrophy leads to
quickly worsening disability. Death
usually occurs by age 25, typically from
lung disorders
Treatments for DMD (1)
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To improve breathing:
 O2
therapy
 Ventilator
 Scoliosis
surgery
 Tracheotomy
Treatments (cont.) (1)
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To improve mobility:
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Physical therapy
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Surgery on tight joints
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Prednisone-ppppppppppppppppppppp
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Non-steroidal medications-oooooo
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Wheelchair
PHYSIOTHERAPY
TREATMENT
AIM TO :
minimize the development of contractures and deformity by
developing a program of stretches and exercises where
appropriate
anticipate and minimize other secondary complications of a
physical nature
monitor respiratory function and advise on techniques to assist
with breathing exercises and methods of clearing secretions
The Beginning of Gene Therapy
for DMD (2)
Advances in Gene Therapy(3)
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Researches have developed "minigenes,"
which carry instructions for a slightly
smaller version of dystrophin, that can fit
inside a virus
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Researchers have also created the socalled gutted virus, a virus that has had its
own genes removed so that it is carrying
only the dystrophin gene
Problems with Gene Therapy(3)
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Muscle tissue is large and relatively
impenetrable
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Viruses might provoke the immune system
and cause the destruction of muscle fibers
with the new genes
COMPLICATIONS
•Cardiomyopathy
•Congestive heart failure (rare)
•Deformities
•Heart arrhythmias (rare)
•Mental impairment (varies, usually minimal)
•Permanent, progressive disability
Decreased mobility
Decreased ability to care for self
•Pneumonia or other respiratory infections
•Respiratory failure
References:
1. “Muscular Dystrophy” PowerPoint by Katherine Kolor, PhD, MS,
CDC Ambassador Program, June 2005.
2. Pobojewski, S. The University Record, November 9, 1998. U-M’s
improved viral vector delivers dystrophin gene to mouse muscle
without major immune Response [online]. 1998. [cited 2005 June
26]. Available at URL:
http://www.umihc.edu/~urecord/9899/Nov09_98/12.html
3. Journey of Love: A Parent’s Guide to Duchenne Muscular
Dystrophy [online]. 2004. [cited 2005 June 22]. Available from
URL: http://www.mdausa.org/publications/journey/5.html
4. Dictionary.com. Lexico Publishing Group, LLC. [online]. 2005.
[cited 2005 June 22]. Available from URL:
http://dictionary.reference.com/