This document discusses Duchenne muscular dystrophy (DMD), a genetic disorder characterized by progressive muscle degeneration and weakness. It is caused by mutations in the dystrophin gene that result in little to no dystrophin protein. Without dystrophin, muscle fibers are damaged and die, leading to muscle weakness, loss of ambulation, and often premature death. The document covers the role of dystrophin in muscle cells, genetic causes, signs and symptoms, diagnostic testing, current treatments focused on symptom management, and associated health complications.

1. INTERNATIONAL SCHOOL
OF MEDICINE
Research studies on Duchenne Muscular Dystrophy.
Presented By:-
Mohammed Abdul Aziz -4th Group
Dinesh Pal Singh- 3rd Group
Tanwee Fatima - 3rd Group
Sana Momin - 3rd Group

2. Definition
Ducchenne muscular dystrophy is most common of
several childhood muscular dystrophies and it is an
inherited disorder ( X-linked recessive ) Characterized
by progressive degeneration of muscle.

5. Dystrophin-Glycoprotein complex:-
 Dystrophin is part of a group of proteins (a protein
complex) that work together to strengthen muscle
fibers and protect them from injury as muscles
contract and relax.
 The dystrophin complex acts as an anchor,
connecting each muscle cell's structural framework
(cytoskeleton) with the lattice of proteins and
other molecules outside the cell (extracellular
matrix).
 Dystrophin provides strength to muscle cells by
linking the internal cytoskeleton to the surface
membrane

6. Its Effect on cell:-
 Dystrophin provides strength to muscle cells by linking the internal cytoskeleton
to the surface membrane. Without this structural support, the cell membrane
becomes permeable.
 Mitochondrial dysfunction gives rise to an amplification of stress-induced
cytosolic calcium signals and an amplification of stress-induced reactive-oxygen
species production. In a complex cascading process that involves several
pathways and increased oxidative stress within the cell damages
the sarcolemma and eventually results in the death of the cell.
 As components from outside the cell are allowed to enter the internal pressure
of the cell increases until the cell bursts and dies.
 Muscle fibers undergo necrosis and are ultimately replaced
with adipose and connective tissue.

7. How Gene Defects:-
 Mutations of dystrophin gene lead to an absence of or defect in the protein
dystrophin, which results in progressive muscle degeneration.
 Mutation of the DMD gene is deletion of 1 or more exons, Duplications ,
nonsense or splice site mutations
 The most common mutation are repeats of the CAG nucleotides.
 Although there is no clear correlation found between the extent of the deletion
and the severity of the disorder, DMD deletions usually result in frameshift.
 Mutations within the dystrophin gene can either be inherited or occur
spontaneously during germline transmission.

8. Disease overview:-
 DMD is a severe type of muscular dystrophy. The
symptom of muscle weakness usually begin around
the age of four in boys and worsens quickly.
 Typically muscle loss occurs first in the upper legs
and pelvis followed by those of the upper arms.
 The disorder is X-linked recessive. Females typically
are carriers for the disease, while males are affected.
A female carrier will be unaware she carries a
mutation until she has an affected son.

9. Symptoms :-
 Delayed Onset
 Walking ,
 Difficulty in performing a standing jump
 Waddling when walking
 Difficulty standing up
 Enlarged Calves ( Pseudo hypertrophy due to fat infiltration )
 Muscle contractures of Achilles tendon and hamstrings impair functionality because the muscle fibers
shorten and fibrose in connective tissue
 Difficulty with motor skills.
 Skeletal deformities (including scoliosis in some cases)
 Higher risk of neurobehavioral disorders
 learning disorders (dyslexia)
 non-progressive weaknesses in specific cognitive skills (in particular short-term verbal memory), which
are believed to be the result of absent or dysfunctional dystrophin in the brain.

10. Signs:-
Gower’s
sign

11. Signs:-

12. Diagnosis:-
 The diagnosis of a dystrophinopathy is suspected based upon:
 Characteristic age and sex
 Presence of symptoms and signs suggestive of a myopathic
process
 Markedly increased serum creatine kinase values
 Myopathic changes on electromyography and muscle
biopsy
 A positive family history suggesting X-linked recessive

13. Serum muscle enzymes:-
 Markedly raised serum CK level, 10-20 times the upper limit of
normal
 – Levels peak at 2-3 years of age and then decline with
increasing age, due to progressive loss of dystrophic muscle
fibres
 Elevated serum ALT, AST, aldolase and LDH

14. Electromyography
 Needle electromyography
 Short duration, low amplitude polyphasic motor unit
potentials in proximal muscles
 Over time, some of these areas become electrically silent

15. Muscle biopsy
 Gold standard for
diagnosis
 Performed when genetic
testing is negative, or the
clinical phenotype is
atypical

16. Molecular Genetic Testing
 Multiplex polymerase chain reaction (PCR),
 Multiplex ligation-dependent probe amplification (MLPA) has
provided a more sensitive technique for detecting deletions.
 If MLPA testing is negative, the DMD gene can be tested for
point mutations.

17. Genetic Analysis
 Molecular genetic testing is indicated for patients with an
elevated serum CK level and clinical findings suggestive of a
dystrophinopathy.
 The diagnosis is established if a disease-causing mutation of the
dystrophin gene (DMD) is identified
 Deletion of one or more exons of DMD gene
 Duplication of one or more exons of DMD
 Small insertions/deletions/point mutations/splicing
mutations of DMD gene

18. Treatment:-
 There is no cure yet for DMD, however case and symptom management is
currently “successful”.
 Treat respiratory problems.
 Treat cardiac problems.
 Glucocorticoids therapy.
 Drugs used to improve muscle strength.
 Utrophin (sometimes can be substituted for dystrophin)

19. 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 .