1. Duchenne’s Muscular Dystrophy
Group A4
Khalil Ali, Mollie Auguste, kajan devamanoharan, Neelima Kaushal,
Presented by: Joy moore, Nickson Omboro

2. X-Linked Recessive XY XX* X*Y XX XX XY XX* XY XY XX XX XX* XX* XY X*Y
Intro & Background: 1min
XX*
XX* XY
X*Y XX XX

3. History
First described by Giovanni Semmola in 1834, and Gaetano Conte in 1836
Named after Guillaume Duchenne for his description, live tissue samples, and case photos in his 1862 Album de Photographies Pathologiques
Moral of the Story: take very good notes, lots of pictures, and PUBLISH
History: 0.5-1min

4. Symptoms
As early as 1 year old, early motor milestones may be met, but often walking is delayed
5 years old, initial proximal limb muscle weakness.
Muscle wasting, difficulty running.
Gower’s sign
Waddling duck-like gait
Later compensatory hypertrophy of distal sites, such as the calf muscles, followed eventually by pseudohypertrophy with increased fibrous tissue and adipose tissue replacing muscles.
Symptoms: 1-2mins

5. Diagnosis Blood: Increased serum CK-MM
Light Microscopy: random variation in muscle fiber size, necrosis of individual muscle fibers, and replacement of necrotic fibers by fibrofatty tissue invaded by histiocytes.
Immunochemical Staining: absence of dystrophin
Confirmatory Muscle Biopsy: characteristic rounded, enlarged fibers without normal cross-striations, fiber necrosis, regeneration and replacement by fat and hyaline
Degenerative and regenerative changes in adjacent myocytes
Diagnosis: 1min

6. Cause
Mutation in Xp21, mostly deletion mutation, the rest are frameshift and point mutations
Can affect any segment of the Dystrophin gene
The given mutation will be constant within families and gives characteristic DNA coding
Deficiency of Dystrophin synthesis, a 427kDa protein
Dystrophin normally present in small amounts in the sarcolemma
Actin-binding transmembrane protein
Stabilizes the sarcolemma and acts as a link between the cytoskeleton and ECM
Targets skeletal muscle tissue, but it may also affect cardiac muscle
Cause 1min

7. Worldwide Prevalence
X-linked recessive, with up to 2/3 as familial cases, and 1/3 resulting from de novo mutation.
Occurs almost entirely in male children, though possible in females
1 : 3,500 infant males
Most common and most severe of the muscular dystrophies

8. Treatment & Management
Prognosis: grim outlook, death usually before age 20
Wheelchair dependent by age years old
Pelvic & shoulder girdle weakness and ataxia progressing to immobilization, wasting, muscle contracture, heart failure, arrhythmias
Death in early teens, most often due to pneumonia from respiratory insufficiency
Female carriers are clinically asymptomatic, but have elevated CK and risk developing dilated cardiomyopathy later in life
Management Goals: protect cardiac muscles and provide respiratory support

9. Future Perspectives
Primarily Longitudinal Research and observational studies
Drug Tolerability & Off-label Efficacy studies in Phases 1 & 2
Myoblast Transplant study now recruiting for Phases 1 & 2
Obstacle: how to introduce a single large gene targeted into all muscle cells without initiation of an immune response to the new gene product

10. Resources https://www.genome.gov/19518854 https://www.mda.org/
Antthony, Douglas, & Matthew Frosch & Umberto de Girolami. “27: Peripheral Nerve & Skeletal Muscle” Robbins & Cotran Pathology, ed 7.
Smith C., Marks A., Lieberman M. Mark's Basic Medical Biochemistry - A Clinical Approach, 2004.
ReesieCup93. “Cole Getting Up Using Gower’s,” YouTube, 2008.