Duchenne Muscular Dystrophy

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DuchenneMuscular Dystrophy

• BRIAN CHANDA CHILUBA
• Dip.PT Cert. NDT
• NEUROLOGY CLASS PRESENTATION

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Overview

• Basic information about Duchenne muscular
  dystrophy
• Inheritance
• Prevalence
• Symptoms
• Treatments

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What Is Duchenne Muscular Dystrophy?(1)

• Genetic
• Progressive muscle weakness
• Defects in muscle proteins
• Death of muscle tissue

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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 (18061875),
  who first described the disease in 1861

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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

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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

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Where is This Gene?
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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 limb-girdle muscular dystrophies) and
dystroglycans. Muscle cells that lack dystrophin
are mechanically fragile, and fail after a few
years, hence progressive muscle weakness.
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Duchenne Muscular Dystrophy Inheritance(1)

• Mother carries the recessive gene and passes it
  to her child
• Trait is usually expressed in
• males only

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Prevalence of DMD(1)

• Affects one in 3500 to 5000 newborn males
• 1/3 of these with previous family history
• 2/3 sporadic

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Symptoms of DMD(1)

• Symptoms usually appear before age 6
• Delayed developmental milestones
• Loss of motor skills
• Characteristic gait
• Calf hypertrophy
• Clumsiness/frequent falls

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More Symptoms of DMD(1)

• Muscle weakness
• Difficulty climbing stairs or hills
• Difficulty rising (Gowers sign)
• Difficulty walking/running

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GOWERS SIGN
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PROGNOSIS
Duchenne muscular dystrophy leads to quickly
worsening disability. Death usually occurs by age
25, typically from lung disorders
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Treatments for DMD (1)

• To improve breathing
• O2 therapy
• Ventilator
• Scoliosis surgery
• Tracheotomy

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Treatments (cont.) (1)

• To improve mobility
• Physical therapy
• Surgery on tight joints
• Prednisone-ppppppppppppppppppppp
• Non-steroidal medications-oooooo
• Wheelchair

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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

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The Beginning of Gene Therapy for DMD (2)
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Advances in Gene Therapy(3)

• Researches have developed "minigenes," which
  carry instructions for a slightly smaller version
  of dystrophin, that can fit inside a virus
• Researchers have also created the so-called
  gutted virus, a virus that has had its own genes
  removed so that it is carrying only the
  dystrophin gene

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Problems with Gene Therapy(3)

• Muscle tissue is large and relatively
  impenetrable
• Viruses might provoke the immune system and cause
  the destruction of muscle fibers with the new
  genes

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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

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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-Ms 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.htm
  l
• 3. Journey of Love A Parents 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/

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