This document provides an overview of Duchenne muscular dystrophy (DMD). It begins with a brief history of the disease and its discovery. It then discusses the genetic basis and pathophysiology of DMD, which involves a mutation in the dystrophin gene. The clinical features and stages of DMD are outlined, from early ambulatory difficulties in childhood to loss of ambulation and eventual death often by the 30s due to respiratory or cardiac failure. Current treatment focuses on symptom management through physical therapy, bracing, medications, and nutritional support, though stem cell therapy and gene therapy show promise.

1. BY ANIEDU, UGOCHUKWU I.
(B.Sc, MD(in view)

2. History
Introduction
Genetics
Pathogenesis
Clinical features/Diagnosis
Prognosis
Treatment
Summary and Conclusion
References

3. The disease was first described by the Neapolitan
physician Giovanni Semmola in 1834 and Gaetano
Conte in 1836
DMD is named after the French neurologist Guillaume
Benjamin Amand Duchenne
In an 1861 publication, Duchenne established the
diagnostic criteria that are still used
William Richard Gowers was the first to deduce the
genetic basis for the disease
In 1986, Louis M. Kunkel provided molecular genetic
confirmation of the X-linked recessive inheritance
pattern

4. The muscular dystrophies are a group of
genetically determined, progressive diseases of
skeletal muscle
They are non-inflammatory and have no
neurological cause
Duchenne muscular dystrophy (DMD) is the most
common muscular dystrophy affecting 1 in 3500
males born worldwide.
Seen in males only (expect in females with
TURNER’S SYNDROME)

5. DMD is inherited in an X-linked recessive
pattern(defect at Xp21 locus)
Females will typically be carriers for
the disease while males will be
affected
The son of a carrier mother has a 50%
chance of inheriting the defective gene
from his mother.
The daughter of a carrier mother has a
50% chance of being a carrier or having
two normal copies of the gene.

6. The disorder is caused by a mutation in
the dystrophin gene, the largest gene
located on the human X chromosome which
codes for the protein dystrophin
Without dystrophin, muscles are susceptible
to mechanical injury and undergo repeated
cycles of necrosis and regeneration.
Ultimately, regenerative capabilities are
exhausted or inactivated

7. Dystrophin is responsible for connecting
the cytoskeleton of each muscle fiber to the
underlying basal lamina
The absence of dystrophin permits
excess calcium to penetrate the sarcolemma
leading to mitochondrial dysfunction
mitochondrial dysfunction gives rise to an
amplification of stress-induced cytosolic calcium
signals and an amplification of stress-
induced reactive-oxygen species (ROS) production.

8. Increased oxidative stress within the cell damages the sarcolemma and
eventually results in the death of the cell.
Muscle fibers undergo necrosis and are ultimately replaced
with adipose and connective tissue

9. Age of onset is between 2-6 years of age
Stage 1 – Presymptomatic
Creatine kinase usually elevated
Positive family history

10. Stage 2- Early ambulatory
clumsy & Waddling gait, manifesting in children aged
2-6 years; secondary to hip girdle muscle weakness
Inexorable progressive weakness in the proximal
musculature, initially in the lower extremities, but
later involving the neck flexors, shoulders, and arms
Meryon’s sign
child slips through examiner’s grasp when lifted under
arms
Possible toe-walking
Can climb stairs

11. Gower's sign
-'climbing up legs' using the hands when rising from the floor

12. Stage 3- Late ambulatory
More difficulty walking
Around age 8 years, most patients notice difficulty with ascending stairs
and respiratory muscle strength begins a slow but steady decline
Cannot arise from the floor
The forced vital capacity begins to gradually wane, leading to symptoms
of nocturnal hypoxemia such as lethargy and early morning headaches

13. 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, especially when more wheelchair dependent
If wheelchair bound and profoundly weak, patients develop terminal
respiratory or cardiac failure, usually by the early 30s
poor nutritional intake can also be a serious complication in
individuals with severe end-stage DMD
Contractures may develop

14. most are unable to ambulate independently by age 10
most are wheelchair dependent by age 15
most die of cardio respiratory problems by age 25-30

15. There is no cure yet for DMD, however
case and symptom management
such as:
• physical therapy
• positioning aids - used to help the
child sit, lie, or stand
• braces and splints - used to prevent
deformity, promote support, or
provide protection
• medications
• nutritional counseling
• psychological counseling
is currently successful

16. Conclusively, there are many clinical trials in process, like
administering Albuterol (beta adrenergic receptor agonist drug
that increases strength and muscle mass) also, they want to
treat with Utrophin (sometimes can be substituted for
dystrophin)
Embryonic stem cell transplants is another treatment they are
looking into. It is hoped that injecting healthy, nonspecialized
stem cells into DMD victims will cause the stem cells to
specialize and produce structurally and functionally correct
dystrophin. If dystrophin can be produced, it may slow the
progression of the disease, or cure it altogether.

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21. THANK YOU