Muscular Dystrophies

1
Muscular Dystrophies

• Robert Yarnall
• Rachel Hanson
• Dustin Jensen-Reiber

2
What is Muscular Dystrophy?

• A category of over 30 genetic diseases
• Duchenne MD (most common)
• Becker MD
• Emery-Dreifuss MD
• Oculopharyngeal MD
• All characterized by escalating muscle weakness
  and deterioration, usually occurring in proximal
  to distal direction due to muscle protein
  abnormality
• DIFFERENTIATION
• muscles affected
• extent of weakness
• onset age
• progression rate
• inheritance pattern

3
Who is affected?

• INHERITANCE PATTERNS
• Recessive e.g. Mm x Mm
• Dominant e.g. Mm x mm
• X-linked e.g. XMXm x XMY
• The most common two forms, Duchenne and Becker,
  are X-linked, so males are almost exclusively
  affected by these two forms
• DUCHENNE MD
• 1 case per 3,500 live male birth -- 121,000 per
  year
• BECKER MD
• 1 case per 30,000 live male births

4
What causes the protein abnormality?

• Muscular dystrophy is a genetic disease
• The root of the problems lies with a defective
  gene. The gene responsible for the production of
  a certain protein
• Transcription
• Transfer of information coded in DNA to mRNA
• Translation
• Conversion of mRNA message to a protein
• If a gene is defective, it will not be able to
  produce the appropriate mRNA strand
• The inappropriate mRNA strand will not produce
  the appropriate protein

5
Common Signs and Symptoms

• Difficulty taking first steps
• Difficulty getting up from sitting or supine
  position
• Gower sign
• Unusual gait
• may walk on toes or balls of feet
• belly pushed out and shoulders back
• Weak muscular strength tests
• Scoliosis

6
Common signs and symptoms

• Loss of ambulation (walking)
• usually occurs between ages of 7-13
• can occur as early as age 6
• Wheel chair needed
• Contractures (often permanent muscle shortening)
• Pseudohypertrophy of muscle
• dead cells replaced by fibro-fatty pad
• High creatine phosphokinase blood levels
• enzyme leaks out of damaged muscle

7
Why do the muscle cells die?

• The muscle cells either completely lack, are
  insufficient in, or have an abnormality relating
  to some form of vital sarcolemma protein
• Dystrophin, Merosin, Fukutin, Caveolin, etc
• Dystrophin
• 3,685 amino acid protein
• accounts for 0.002 of proteins in striated
  muscle
• This abnormality in muscle fiber membrane
  proteins disrupts the structural integrity of the
  cell
• Dystrophin links with actin proteins and DAG
  complex (dystrophin associated glycoproteins) to
  create a stable complex that interacts with
  extracellular matrix
• Cell contents leak out, eventually causing cell
  death

8
Analogy

• The whole muscle cell is a building
• contains many different components
• One component being bolts
• dystrophin (or another structural protein) are a
  certain type of bolt in the building
• If this bolt is nonexistent or lacking in number,
  the structural integrity of the building suffers
• the cell membrane suffers
• The building may even collapse
• the cell dies