Duchenne Muscular Dystrophy (DMD) is a progressive muscle degeneration and weakness caused by a mutation preventing the production of dystrophin, primarily affecting 1 in 3500 males due to its X-linked recessive inheritance. The disease typically manifests between ages 2-6, leading to difficulties in mobility and respiratory function, with most patients becoming wheelchair-dependent by age 15 and facing life expectancy issues due to cardiac and respiratory problems. Currently, there is no cure for DMD.

1. Duchene Muscular Dystrophy
Bilal Sami Al-Mosheqah

2. Learning Objectives
Definition
Causes Clinical Feature
Pathogenesis

3. Definition
Progressive muscle degeneration and weakness. It is one of nine types
of muscular dystrophy.(most common and sever clinical symptoms)
The muscular dystrophies are a group of genetically determined, progressive
diseases of skeletal muscle.
The most common muscular dystrophy affecting 1 in 3500 males born worldwide .
DMD is inherited in an X-linked recessive pattern

4. Genetics
The gene that can carry a DMD-causing mutation is on the X
.chromosome (defect at Xp21 locus)
Females are 46 XX
Males are 46 XY
will typically be carriers
will be affected
This is going to cause a mutation that prevents the body
from producing Dystrophin ?

5. Dystrophin
Dystrophin gene the largest known human gene (vulnerable to mutation)
Is a protein located between the sarcolemma and the outermost layer of
myofilaments in the muscle fiber
It is a cohesive protein, linking actin filaments to another support protein that
resides on the inside surface of each muscle fiber’s plasma membrane
Role of Dystrophin protein
 Supports and strengthen muscle fibers
 Protect them from injury as muscles contract and relax

6. Pathogenesis
Dystrophin links the muscle cells to the extracellular matrix stabilizing the membrane
and protecting the sarcolemma from the stresses that develop during muscle contraction
Mechanically induced damage through eccentric contractions puts a high stress on fragile membranes
and provokes micro-lesions that could eventually lead to loss of calcium homeostasis, and cell death
Imbalance between necrotic and regenerative processes: early phase of disease
Later phases the regenerative capacity of muscle fibers are exhausted and fibers are gradually
replaced by connective tissue and adipose tissue.
Pseudohypertrophy

15. Microscopy
Cross section of muscle shows extensive replacement of
muscles fibers by fat cells.
Normal muscle fibers

16. Clinical Features
Age of onset is between 2-6 years of age
 Presymptomatic Creatine kinase usually elevated
 Positive family history
Stage 1
Stage 2(Early ambulatory)
 Clumsy & waddling gait(secondary to hip girdle muscle )
 Possible toe-walking
 Gower's sign
 Can climb stairs
Gower's sign
waddling gait

17. Clinical Features
Stage 3 (Late ambulatory)
 More difficulty walking Around age 8 years
 most patients notice difficulty with ascending stairs
 respiratory muscle strength begins a slow but steady decline
 Cannot arise from the floor
Stage 4 (Early nonambulatory)
 Can self-propel for some time
 Able to maintain posture
 Possible development of scoliosis
Stage 5 (Late nonambulatory)
 Scoliosis may progress
 patients develop terminal respiratory or cardiac failure,
.usually by the early 30s
Main cause of short life span

18. Prognosis
1.most are unable to ambulate independently by age 10
2.most are wheelchair dependent by age 15
3.most die of cardio respiratory problems by age 25-30
There is no cure yet for DMD

19. Summary
DMD is progressive muscle degeneration and weakness
DMD is a result of mutation that prevents the body from producing dystrophin
Affecting 1 in 3500 males because it is x-linked
Patients with DMD have short life span as result of cardiac and respiratory complications

21. References
Robbins Basic Pathology
Textbook of Pathology