2. Introduction
Sample Footer Text
Duchenne muscular dystrophy (DMD) is a genetic disorder
characterized by progressive muscle degeneration and
weakness due to the alterations of a protein called
dystrophin that helps keep muscle cells intact
DMD symptom onset is in early childhood, usually between
ages 2 and 3. The disease primarily affects boys, but in
rare cases it can affect girls.
DMD has an X-linked recessive inheritance pattern.
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3. • Becker muscular dystrophy (BMD) is similar to DMD, but with onset usually in the teens or
early adulthood. The disease course for BMD is slower and less predictable compared to
DMD
4. History
• DMD was first described by the French neurologist Guillaume Benjamin Amand Duchenne in
the 1860s.
• In 1986, MDA-supported researchers identified a particular gene on the X chromosome that,
when flawed (mutated), leads to DMD.
• In 1987, the protein associated with this gene was identified and named dystrophin. Lack of
the dystrophin protein in muscle cells causes them to be fragile and easily damaged.
5. Clinical features
• Muscle weakness is the principal symptom of DMD.
• It can begin as early as age 2 or 3, first affecting the proximal muscles and later affecting the
distal limb muscles.
• Usually, the lower limb muscles are affected before the upper limb muscles.
• The affected child might have difficulty jumping, running, and walking.
• Enlargement of the calves- pseudohypertrophy
• Waddling gait
6. • Lumbar lordosis ( inward curve of the spine)
• Decreased endurance, frequent falls
• Inability to keep up with peers
• Muscle pain, cramping
• DMD is associated with increased chance of Autism spectrum disorder, ADHD, OCD, Anxiety
• Patients become wheelchair bound by age 12-13 years and die by age 20-30 years from
respiratory insufficiency and cardiomyopathy
9. Investigations
• 1) Increased serum CK
• High levels of CK may be found before the onset of symptoms, even in newborns affected by
DMD.
• The CK level peaks (at 10 to 20 times the upper limit value) by age 2, then progressively falls
at a rate of 25% per year, eventually returning to normal level when a considerable amount of
muscle tissue has been replaced by fat and scar/fibrotic tissue.
• AST and ALT are also Increased
10. Genetic testing
• Usually genetic diagnosis is indicated for patients with elevated serum CK levels and clinical
findings of dystrophinopathy
• Diagnosis is confirmed if a mutation of the DMD gene is identified.
• Multiplex ligation-dependent probe amplification (MLPA) has been one of the main techniques
for the detection of deletions and duplications of the DMD gene.
• If initial genetic analysis is negative, the analysis of small and micro deletion/duplication gene
mutations is next
• Female relatives of men and boys with DMD can undergo DNA testing to see if they are
carriers of the disease
11. Muscle biopsy
• Use of the biopsy is to distinguish muscular dystrophies from inflammatory and other
disorders, and to distinguish among different forms of muscular dystrophy.
• For instance, the amount of functional dystrophin protein found in a muscle biopsy sample
sheds light on whether the disease course is likely to be DMD, with no dystrophin present, or
the milder Becker muscular dystrophy (BMD), with some partially functional dystrophin
present.
• If the suspicion of DMD remains high despite negative genetic analysis, dystrophin detection
by western blot technique or staining with selective antibodies is carried out in the tissue
derived from a muscle biopsy
12. ECG and ECOCARDIOGRAPHY
• 1) ECG
• Arrhythmia cam be seen
• 2) ECHOCARDIOGRAPHY
• Significant mitral regurgitation is often present due to involvement of the posterior
papillary muscle
• The incidence of symptomatic cardiomyopathy in patients with DMD increases
gradually in the teenage years; it is defined as left ventricular ejection fraction less than
55 percent.
13. Xray
• Xray can show fractures due to frequent falls
• Scoliosis
14. Electromyography
• With both DMD and BMD, electromyography reveals myopathic changes, usually consisting of
small polyphasic potentials.
• However, electromyography is almost never used in the diagnosis of DMD and BMD.
15. Differential diagnosis
• 1) Limb-girdle muscular dystrophy
• The distinction between BMD and limb-girdle muscular dystrophy (LGMD) is often hard to
make in patients with a negative family history for BMD.
• However, the calf muscle pseudohypertrophy is usually not as striking in LGMD.
• Caused by a mutation in the FKRP gene
• 2) Emery-Dreifuss muscular dystrophy
• Onset of symptoms from EDMD usually occurs in the first or second decade of life.
16. • 3) Spinal muscular atrophy
• Characterized by degeneration of the anterior horn cells in the spinal cord and motor nuclei in
the lower brainstem, which results in progressive muscle weakness and atrophy.
• Weakness is predominately proximal and affects the legs more than the arms.
• Additional manifestations include sparing of face and eye muscles, tongue atrophy with
fasciculations, areflexia, a fine tremor-like form of myoclonus (minipolymyoclonus) affecting
distal limbs, dysphagia, and respiratory insufficiency
• Other features of SMA that help distinguish it from DMD include diffuse areflexia or
hyporeflexia, modest CPK elevation, tongue fasciculations, and a neurogenic
electromyography pattern.
17. Management
• STEROIDS
• Glucocorticoids are the mainstay of pharmacologic treatment for DMD because of their
beneficial effects for improving motor function and pulmonary function, reducing the risk of
scoliosis, delaying the loss of ambulation, and possibly for delaying progression of
cardiomyopathy and improving survival
• Prednisolone . Dose 0.3-0.75 mg/kg/day
• Deflazacort. Dose 0.9 mg/kg/day
18. • Immunization
• Ensure immunizations against – Pneumococcus, influenza and varicella before initiating
steroid therapy
19. Cardiac care
• Dilated cardiomyopathy with LVEF < 55%
• ACE Inhibitors
• ARBs
• They both make the blood vessels wide open and decrease the resistance to heart
• Diuretics can remove extra water from body so there is less volume for heart to pump
• Beta blockers- they decrease HR, giving the heart more time to empty and refill
20. RESPIRATORY MANAGEMENT
• Respiratory complications include respiratory muscle fatigue, atelectasis, mucous plugging,
pneumonia, and respiratory failure
• The core respiratory therapies for DMD are lung volume recruitment, assisted coughing,
nocturnally assisted ventilation, and subsequent daytime ventilation .
• These therapies are associated with prolonged survival
21. Orthopedic care
• Lightweight plastic ankle-foot orthoses should be applied if the foot remains in plantar flexion during sleep.
•
• ●Standing and/or walking may be maintained by using long-leg braces.
•
• ●Surgery may be performed to release contractures of the hip flexors, iliotibial bands, and Achilles tendons.
•
• ●Standing and ambulation may prevent scoliosis
•
• ●Wrist or hand splints for stretching of wrist and long finger flexors and extensors may be helpful in
nonambulatory phases.
22. Exercise
• Boys with DMD who are ambulatory or in the early non-ambulatory stage should participate in
regular submaximum (ie, gentle), aerobic exercise to avoid disuse muscle atrophy, immobility,
excessive weight gain, and social isolation
23. Diet and nutrition
No special dietary restrictions or additions are known to help in DMD. Most doctors recommend
a diet similar to that for any growing boy but with a few modifications.
• However, some suggest the intake of dietary calcium and vitamin D in the form of dairy
products, other foods rich in calcium, a supplementation, and sunshine exposure.
24. Psychosocial care
• For DMD and Becker muscular dystrophy (BMD), psychosocial care includes routine
assessment of the mental health of the patient and family at every clinic visit, with ongoing
support and referrals to a psychiatrist or psychologist if needed
25. NEW THERAPIES UNDER CLINICAL TRIALS
1) Inserting new dystrophin genes
Gene replacement therapy delivers a healthy gene directly to the patient’s tissue, substituting
the flawed gene.
To accomplish gene transfer in DMD, some researchers aim to utilize the action of viruses. A
virus works by inserting its own genetic material into a host.
Scientists have inserted a smaller version of the dystrophin gene into the virus so the virus will
deliver the dystrophin gene into muscle cells to manufacture dystrophin protein.
26. References
• Ghai Essential Pediatrics
• Davidson’s Principles and Practice of Medicine
• www.mda.org
• www.uptodate.com
