Muscular dystrophy is a group of inherited progressive disorders caused by defects in genes required for normal muscle function. The document focuses on Duchenne muscular dystrophy and Becker muscular dystrophy, which result from mutations in the dystrophin gene located on the X chromosome. Duchenne muscular dystrophy is more severe and common, causing weakness starting at age 2-3 and loss of ambulation by age 12. Becker muscular dystrophy has a milder course with ambulation beyond age 15 but reduced life expectancy. Management involves physiotherapy, occupational therapy, treatment of cardiac and respiratory complications, and steroids which can prolong ambulation in Duchenne muscular dystrophy.

1. MUSCULAR DYSTROPHY

2. An inherited group of progressive myopathic disorders resulting
from
defects in a number of genes required for normal muscle function

3. Mutations of the dystrophin gene (so named dystrophinopathies)
X-linked recessive traits
Clinical phenotypes
1. Duchenne muscular dystrophy (DMD)
2. Becker muscular dystrophy (BMD)
3. Intermediate Phenotype ((between DMD and BMD)
4. DMD-associated dilated cardiomyopathy
• Principal symptoms : Progressive weakness (muscle fiber degeneration)

4. •Pathology

5. # Dystrophin
- At cytoplasmic face of muscle
cell
- Complexes with Dystroglycans
and sarcoglycans
Dystrophin-glycoprotein complex
– provide stability to sarcolemma
(Deficiency of one member of the
complex may cause abnormalities
in other components)

6. • Disruption of the dystrophin-glycoprotein complexes weakens the
sarcolemma, causing membrane tears and a cascade of events
leading to muscle fiber necrosis.
This sequence of events occurs repeatedly during the life of a
patient with muscular dystrophy.
• That’s why, progressive weakness as a principal
symptom

7. 1. DUCHENNE MUSCULAR DYSTROPHY
• Histologic and lab findings- evident at birth (in boys)
# Clinical Findings
 Weakness
• 2-3 Y age - onset of weakness (slow and ungainly run)
• 12 Y age – Wheel chair bound (scoliosis and poor pulmonary function)
• Selectively affect : proximal limbs muscle > distal limbs muscle
: lower >upper extremities
• Gross motor delay, inability to keep up with peers, loss of motor skills, and muscle
pain or cramping (early)

8. Physical examination
• Growth delay ( Short stature )
• Pseudohypertrophy of the calf and (occasionally) quadriceps
muscles,
• Lumbar lordosis,
• A waddling gait,
• Shortening of the Achilles tendons,
• Hypotonia, and Hyporeflexia orAreflexia.

9. Gower’s Sign

10.  Cardiomyopathy
a. Primary dilated cardiomyopathy (DCM)
- Postero-basal left ventricular wall (Extensive fibrosis)
- ECG changes : Tall R wave (precordium) with increase R/S ratio,
: deep Q wave (I, aVL, and V5-6)

12. b. Conduction abnormalities
- Intra-artrial and Interatrial conduction; Arrhythmias (supraventricular)
 Cardiomyopathy frequency
1/3rd at 14 Y age
½ at 18 Y age
All in >18 Y age
Heart failure and arrhythmias may develop in the late stages of the disease,
especially during intercurrent infections or surgery

13. • Wheelchair by about age 13 years and
• Death in their late teens or twenties from respiratory
insufficiency or cardiomyopathy;
• Only a few DMD patients survive beyond the third
decade
CLINICAL COURSE

14. 2. BECKER MUSCULAR DYSTROPHY (BMD)
• Less severe form of X-linked recessive muscular dystrophy
• 10 times less frequent than DMD
Clinical features
• Similar to DMD
• Hypertrophy of muscles, particularly in the calves, is an early and prominent finding.
• patients with Becker dystrophy walk beyond age 15, whereas patients with Duchenne
dystrophy are typically in a wheelchair by the age of 12
• have a reduced life expectancy, but most survive into the fourth or fifth decade
• Mental retardation may occur in Becker dystrophy, but it is not as common as in
Duchenne

15. Features DMD BMD
Age of
presentation
Usually 1-4 years Later
Molecular defect Absent dystrophin protein Qualitative/ quantitively
abnormal dystrophin
protein
Incidence ~30/100,000 live male birth ~10 times< frequent
than DMD
Severity Clinically severe Clinically milder
Ambulation Patient is in wheel chair by age of
12 yrs
Ambulatory even at 12
yrs of age
Learning disability More frequent Less frequent
Death Usually by the end of 2nd decade Much later
BMD VS DMD

16. DIFFERENTIAL DIAGNOSES
• Limb-girdle muscular dystrophy
• Emery-Dreifuss muscular dystrophy
• Spinal muscular atrophy

17. •Investigations

18. When to suspect diagnosis
• Any evidence of delayed motor milestones in a young child with a
positive family history of DMD
• When there is no family history of DMD, a child not walking by 16 to
18 months, or the presence of Gower's sign, toe walking, or calf
hypertrophy (see 'Weakness' above)
• Unexplained increases in transaminases (eg, aspartate transaminase
and alanine transaminase)

19. INVESTIGATIONS
• CK level
• Genetic analysis
• Dystrophin analysis
• Electromyography (EMG)- for muscle's electrical activity
• Muscle biopsy,
• ECG, and/or ECHO

20. •Management

21. • No specific therapy for these conditions
• Physiotherapy and occupational therapy help patients cope
with disability
• Treatment of associated cardiac failure or arrhythmia
• Management of respiratory complications (including
nocturnal hypoventilation)
• Genetic counseling is important

22. • primary treatment - Steroids
• Dose: Prednisone 0.75 mg/kg/day for upto 3 yr
Deflazacort 0.6 mg/kg/day
• Generally offered to boys with age >5 yrs.
• Side effects: wt gain, facial swelling, decrease in ht., osteoporosis, fractures,
acne, excessive hair growth, GI symptoms & behavioral change
The use of glucocorticoids has not been adequately studied in Becker
dystrophy

23. REFERENCES
• Casper et al, Harrison’s Principles of Internal
Medicine, 19th edition.
• Up to Date, last updated: Aug 21, 2017

24. •Thank you