Duchenne muscular dystrophy is a genetic disorder characterized by progressive muscle weakness. It is caused by mutations in the gene encoding dystrophin, and mainly affects boys. Clinical features include difficulty walking, calf pseudohypertrophy, loss of ambulation by age 12, wheelchair dependence, scoliosis, and death often by age 18 from respiratory or cardiac failure. Diagnosis involves elevated creatine kinase levels, muscle biopsy showing dystrophin deficiency, and genetic testing. There is no cure, but management focuses on maintaining mobility and function.

1. Neuromuscular Disorders –
Duchenne and Becker’s Muscular
Dystrophy
Dr. Kalpana Malla
MD Pediatrics
Manipal Teaching Hospital
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2. Neuromuscular disorders
Consists of - Motor neuron in brain stem
- Ventral horn of spinal cord
- Its axon with other axon forms
peripheral nerve
- Neuromuscular junction
- All muscle fibers innervated by
single motor neuron

3. May be
• Genetic
• Congenital
• Acquired
• Acute
• Chronic
• Progressive
• Static

4. Myopathy
• Proximal distribution of weakness and muscle
wasting except- myotonic muscular dystrophy
• Slow progression
• Tendon reflexes – preserved
• Sensation – intact

5. Neuropathy
• Distal distribution (except- juvenile spinal
muscular atrophy
• Acute onset
• Tendon reflexes – lost
• Sensory abnormalities –neuropathy

6. Classification
1. Muscular dystrophies:
-X-linked recessive -Duchenne / becker
Limb –girdle MD
- Cong muscular dystrophies
- Facioscapulohumeral
- Oculopharyngeal
- Myotonic dystrophy
- Scapuloperoneal dystrophy

7. Classification
2.Disorder of neuromuscular junction
- Myesthenia gravis
3.Myotonic syndromes
4. Myopathies
a ) Congenital myopathies
b ) Endocrine
- Hypothyroidism
- Hyperparathyroidism

8. Classification
b ) Endocrine - Steroid-induced
- Hyperaldosteronism
C ) Metabolic – K-related periodic paralysis
- Mitochondrial disorders

9. Classification
5. Inflammatory myopathies (myasthitis):
A. Idiopathic – Juvenile dermatomyositis
- polymyositis
B. Infectious – viral, parasitic, bacterial, fungal
6. Floppy infant syndrome

10. Evaluation
Clinical –
• Muscle – bulk, tone ,power,
• Head lag
• See involvement of face, tongue, palate ,extra-
ocular muscles
• Fasciculations – sign of denervation

11. Evaluation
• Undescended testes, funnel shaped thorax -
congenital NMD
• Generalized hypotonia, delayed motor
development

12. Laboratory findings
• Serum enzymes – CPK
• Nerve conduction velocity- motor & sensory
conduction measured electrophysiologically
• Electromyelography - records maximum
voluntary contraction of muscle

13. Laboratory findings
• Muscle biopsy – most important, specific and
diagnostic (Vastus lateralis)
• Nerve biopsy (sural nerve)
• ECG-cardiac evaluation in myopathies

14. Duchenne muscular
dystrophy

16. 16

17. What is Duchenne Muscular Dystrophy?
• The disease characterized by:
- Early onset often before school age
- Progressive muscular deterioration and
death by 14 - 18 years of age
- Defect on a large gene on X chromosome
17

18. Duchenne Muscular Dystrophy
• Commonest muscular dystrophy
• Incidence- 1/3600 male birth
• Inheritance – X- linked recessive
30% - new mutations
sporadic
18

19. FACTS
• The abnormal gene is on the X chromosome at the
Xp21 locus
• Becker muscular dystrophy is the same
fundamental disease as Duchenne dystrophy, with a
genetic defect at the same locus, but clinically it
follows a milder and more protracted course

20. X-Linked recessive
Features-
1.Only males are affected. All his daughters will be
carriers as they receive abnormal X from father
2. Will not manifest in females- 50% sons affected
50% daughters will be carriers when the mother is a
carrier
20

21. 21

22. 22

23. X-Linked recessive
3.Normal sons do not transmit disease
4.Pattern of inheritance is oblique as only males
on the maternal side are affected
5.Females may be affected when affected male
marries a carrier female/or when only one X
chromosome is present
23

24. 24

25. X-Linked recessive
6. Fresh mutations are known
7. Carriers may have biochemical
abnormalities
25

26. • A muscular dystrophy is distinguished from all
other neuromuscular diseases by four obligatory
criteria:
(1) It is a primary myopathy
(2) It has a genetic basis
(3) The course is progressive
(4) Degeneration and death of muscle fibers occur
at some stage in the disease

27. DMD - Muscle wasting
• In DMD - attachment of muscle fibers to their surrounding
endomysium (extracellular matrix) becomes weakened due
to mutations in the dystrophin gene.
• The absence of dystrophin leads to increased death and
destruction
• In turn, scar tissue (a mix of collagen and blood vessels)
replaces the muscle fibers, and it can gradually contract
leading to increased muscle rigidity

28. Clinical features
• Asymptomatic at birth - Early gross motor skills (
rolling over, sitting, standing) may be normal or
mildly delayed
• Poor head control in infancy may be the first sign
of weakness
• Walking achieved at the normal age - but hip girdle
weakness may be seen in subtle form as early as
the 2nd year - waddling gait

29. Clinical features
• Weakness starts in pelvic girdle- Extensor
muscles of back affected – lordosis to stabilize
spine by bony opposition
• Toddlers may assume a lordotic posture when
standing to compensate for gluteal weakness.
• Cannot bend forward without falling

30. • Presents – 2- 4 yrs
• Frequently falls, has difficulty getting up,
climbing stairs or getting in and out of a car
• An early Gower’s sign is often evident by age 3
yr and is fully expressed by age 5 or 6 yr

31. Gets up climbing up his legs- Gower’s sign

32. • Enlargement of the calves
(pseudohypertrophy) and wasting of thigh
muscles is a classic feature.
• Next most common site of muscular
hypertrophy - tongue, forearm.

33. • Pseudohypertrophy also seen - triceps,
quadriceps
• Pseuhypertrophy of muscle fibers - infiltration
of muscle by fat, and proliferation of collagen.
• Fasciculations of the tongue do not occur.

34. • Pseudohypertrophy seen in
supra, infraspinatus, deltoids
– Valley sign
34

35. Clinical features
• Hypertrophy of calf muscles with
tightening of tendo achillis-toe walking
• By 8 yrs –walking becomes difficult
• Knee jerks disappear early but ankle jerk may be
preserved
• Positive valley sign

36. Clinical features cont.
• By 12 yrs – wheel chair bound –
• Loss of lordosis - lose stabilization of spine
↓
Tendency to tilt to one side
↓
Develop– Scoliosis
↓
Bunching of ribs leads to E. reflux with acute
esophagitis, hematemesis, aspiration
pneumonitis 36

37. Clinical features cont.
• Intellectual impairment in all
• 20- 30% - IQ < 70
• Cardiac muscle may be affected –
Cardiomyopathy
• Die by 18 yrs – respiratory failure, pneumonia,
aspiration, heart failure
37

38. Clinical features
• By 12 yrs –wheel chair bound – loss of lordosis
lose stabilization of spine – tendency to tilt to
one side - develop –scoliosis-bunching of ribs
leads to E. reflux with acute esophagitis,
hematemesis, aspiration pneumonitis
• Contractures most often involve the ankles,
knees, hips, and elbows.
• Scoliosis is common.

40. • The function of distal muscles is usually well
preserved - child can continue using eating
utensils, a pencil, and a computer keyboard.
• Respiratory muscle involvement - weak and
ineffective cough, frequent pulmonary infections
• Pharyngeal weakness - episodes of
aspiration, nasal regurgitation of liquids, and an
airy or nasal voice quality
• Extraocular muscles - well preserved

41. • Death occurs usually at about 18 yr of age.
• The causes of death are respiratory failure in sleep,
intractable heart failure, pneumonia, or
occasionally aspiration and airway obstruction

42. Laboratory findings
• Serum creatinine phosphokinase (CPK)  even in
presymptomatic stages, including at birth
> 10,000 units ( range 15,000 – 35,000 IU/L)
Normal level < 160 IU/L
- In severe cases, maybe lower
• Other lysosomal enzymes of muscles:
Aldolase, Aspartate aminotransferase –
increased (less specific)
42

43. EMG
• Electromyography (EMG) shows characteristic
myopathic features but is not specific for Duchenne
muscular dystrophy
• Nerve conduction velocity- normal, No evidence of
denervation

44. Muscle biopsy –
• Diagnostic (Vastus lateralis/ Gastrocnemius)
Myopathic changes –
• endomysial connective tissue proliferation
• Scattered degenerating and regenerating myofibers
• Foci of mononuclear inflammatory cell infiltrates

45. Muscle biopsy
45

46. Others
• Cardiac evaluation
• CXR
• ECG
• ECHO
• Molecular genetic diagnosis –
Immunohistochemical staining of section of
muscle biopsy or by DNA analysis from
peripheral blood -- absent dystrophin
46

47. • Molecular genetic diagnosis - demonstrating
deficient or defective dystrophin by
immunohistochemical staining of sections of
muscle biopsy

48. Treatment
• No medical cure or a method of slowing its
progression.
• To improve mobility:
– Physical therapy
– Surgery on tight joints
– Prednisone
– Non-steroidal medications
– Wheelchair

49. Management
Multidisciplinary approach:
• Exercise – physical exercise, physiotherapy
• Dietary – prevent obesity
• Orthopedic
• Psychological
• Education
• Genetic counselling
49

50. • Physiotherapy delays but does not always
prevent contractures.

51. • Preservation of a good nutritional state
• Adequate calcium intake - to minimize
osteoporosis
• sedentary children burn fewer calories than active
children and depression is an additional factor –
these children tend to eat excessively and gain
weight – Obesity makes a patient with myopathy
even less functional

52. Management
• Pharmacological-treat complication
• Suggestion – To reduuce rate of deterioration
cyclical ( 10 days /month)-catabolic steroid –
prednisolone low dose -decreases the rate of
apoptosis and may decelerate the myofiber
necrosis
• Cyclosporin – under study

53. Some approaches
• Experimental approach – Myoblast transfer
therapy
• Unproven approach – I/M injection of
recombinant dystrophin gene
• "minigenes," which carry instructions for a
slightly smaller version of dystrophin
53

54. Advances in Gene Therapy
• Researchers - created the so-called gutted
virus, a virus that has its own genes removed
so that it is carrying only the dystrophin gene

55. To improve breathing:
• Pulmonary infections should be promptly
treated.
• O2 therapy
• Ventilator
• Scoliosis surgery
• Tracheotomy

56. • Cardiac decompensation often responds well to
digoxin, at least in early stages.
• Immunizations for influenza virus and routine
vaccinations are indicated.

57. GENETIC COUNCELLING
• Prenatal diagnosis for women having risk
pregnancies - with a family history of muscular
dystrophy.
• Identification of dystrophin gene exon deletions
in a male fetus - Couples may elect to terminate
the pregnancy if the fetus is affected.
• Carrier status may be determined in the mother
and siblings of the proband.

58. Becker muscular dystrophy
• This Ds was first described by Becker and Klener in
1955
• X-linked recessive
• Late onset – ambulatory till late adolescence
• Calf pseudohypertrophy, cardiomyopathy, increased
CPK are similar to DMD
• Learning disabilities are less
• Death – in late 20s but severely disabled; fewer than
half of patients are still alive by age 40 yr

59. Dermatomyositis
Pathognomonic feature -Gottron's
papules overlying the dorsal
interphalangeal joints.

60. Gottron's sign:
Erythematous or
violaceous atrophic
macules and
plaques overlying
the dorsal
interphalangeal
joints and sparing
the interphalangeal
spaces

61. Heliotrope
Characteristic finding a violaceous
eruption with periorbital edema.

62. Shawl sign. Poikilodermatous macules appear in a
"shawl" distribution over the shoulder, arms and
upper back

63. Mechanic's hand.
Fissured, scaly, hyperkeratotic and
hyperpigmented hands are suggestive of
manual labor

64. Thank you
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