Lecture 32 - Clinical Aspects of Duchenne Muscular Dystrophy Flashcards Preview

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Flashcards in Lecture 32 - Clinical Aspects of Duchenne Muscular Dystrophy Deck (55):
1

Examples of dystrophinopathies
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1) Duchenne muscular dystrophy
2) Becker muscular dystrophy
3) Familial cramps and myalgia syndrome
4) X-linked dilated cardiomyopathy
5) Elevated creatine kinase
6) Manifesting female carriers
7) Isolated quadriceps myopathy

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DMD age of onset

Under 5 years

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BMD age of onset

Over 5 years

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DMD incidence

1/3,500 males

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BMD incidence

1/35,000 males

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When is a DMD clinical diagnosis normally made?

Between 2 and 4 years

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DMD age of wheelchair dependency

Under 13 years

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BMD age of wheelchair dependency

Over 16 years

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Clinical presentations of DMD
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1) Delayed motor milestones
2) Gait difficulties
3) Fatiguability, frequent falls
4) Calf, thigh cramps, muscle hypertrophy
5) Speech, learning delays
6) Muscle atrophy can occur

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Delayed motor milestones in DMD

Mean age of walking is around 18 months
DMD delays to beyond 18 months

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DMD gait difficulties
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1) Broad-based, waddling gait
2) Proximal weakness
3) Trouble climbing steps
4) Gowers' sign
5) Persistent toe walking
6) Sometimes flat feet

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Physical examination of a DMD patient
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1) Waddling gait
2) Proximal weakness
3) Enlarged, rubbery muscles (calves, sometimes quads, gluteal, deltoids, tongue), hypertrophy, later pseudohypertrophy
4) Facial muscles spared
5) Extra-ocular muscles always spared
6) Weak neck flexors
7) Lumbar lordosis

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Why can DMD lead to cognitive impairments?

Isoform of dystrophin is in the CNS

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Pseudohypertrophy

Apparent enlargement of muscles due to fat deposition and fibrosis

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Gowers' sign
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1) Ask child to lie on back, stand up
2) Normal will flex hips, stand
3) DMD will roll on front, push themselves up, extend hips by pushing on thighs with hands
4) Demonstrates proximal weakness in children over 4 years
5) Normal in children under 3
6) Non-specific

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Why is Gowers' sign non-specific?

It is a feature of any muscle disorder causing proximal weakness
EG: DMD, BMD, myotonic dystrophy, congenital myopathies, myopathies of adulthood, such as steroid myopathy

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How is DMD diagnosed?
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1) Serum creatine kinase level is over 10,000IU/L
2) Thyroid function tests (from blood, will look similar to hypothyroidism)
3) Genetic testing with MLPA
4) Muscle biopsy when there is a suspicion of DMD, but genetic tests are negative
5) If a patient looks like they have DMD, but have normal creatine kinase levels, then they probably have a different muscle condition

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Normal creatine kinase level

Under 200 IU/L

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What can MLPA not detect?

Point mutations, which account for 10-15% of mutations leading to DMD

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How often is a muscle biopsy necessary to diagnose DMD?

Around 1/3 of the time

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3-6 years with DMD
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1) Muscle weakness, but overall strength might increase
2) Increasing disparity between patient and his peers

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8 years with DMD
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1) Increasing fatiguability
2) Unable to run and jump (probably never able to jump)
3) Increasingly prominent lumbar lordosis
4) Progressive contractures of Achille's heel, hips, ilio-tibial band

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10-13 years with DMD

Wheelchair use

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When does cardiac or respiratory failure occur in DMD?

Late teens to early 20s

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Course of DMD
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1) Variable
2) Ambulation lost between 8 and 14 years
3) Gradual decline in upper limb function (difficulty bringing hands to mouth by 16-18 years)
4) Death at around 25 years

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Causes of death in DMD
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1) Most commonly respiratory failure
2) ~10% of deaths are cardiac failure

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When does lumbar lordosis normally present in DMD?

6 years of age

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BMD age of onset

After 5 years
Normally between 5-15 years

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BMD natural history
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1) Onset between 5 and 15 years (can be as late as 3rd or 4th decade)
2) Progressive limb girdle weakness
3) Calf pain, myalgias
4) Able to walk after 15 years
5) Respiratory failure after 4th decade
6) Cardiomyopathy more common than DMD

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Why is cardiomyopathy more common in BMD than in DMD?

There is more strain placed on the heart in BMD, as the patient is less likely to be wheelchair bound early in life

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DMD respiratory failure natural history
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1) Caused by the weakness of intercostal muscles and diaphragm
2) In early years, vital capacity increases with growth
3) In early teens, vital capacity plateaus and declines (5-10% per year)
4) Respiratory failure in late teens, early 20s

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What leads to contractures?

Failing to maintain full range of motion of a joint.
Contracture in DMD often flexion

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Which type of lung disease does DMD cause?

Restrictive lung disease

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First respiratory problem in DMD

Sleep-disordered breathing

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In all neuromuscular disorders, when is breathing the worst?

During REM sleep

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When is sleep disordered breathing the worst?

During REM sleep and disorders affecting diaphragm function

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How does sleep disordered breathing present?
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1) Tiredness, headache
2) Fatiguability, poor concentration, poor school performance
3) Doesn't cause shortness of breath or cough
4) Progresses to nocturnal and daytime hypoventilation

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Which aspect of sleep disordered breathing leads to symptoms?

CO2 retention, not hypoxia

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Obstructive lung disease
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1) From obstruction of the airways
2) Results in a decreased FEV1

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Restrictive lung disease
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1) Normal expiratory rate compared to vital capacity
2) Reduced vital capacity
3) From reduced expansion of lung parenchyma and reduced volume

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Two types of restrictive lung disease

1) Chest wall disorders - Neuromuscular diseases, severe obesity, kyphoscoliosis
2) Chronic interstitial and infiltrative diseases - Pneumoconiosies, interstitial fibrosis

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Atelectasis

Decreased ventilation of a part of the lung leads to collapse of that part.
Increased risk of bacterial infection

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Respiratory failure in late DMD
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1) Nocturnal and daytime hypoventilation, nocturnal hypoxia
2) Poor inflation and emptying of lungs leads to atelectasis, pneumonitis
3) Loss of respiratory reserve correlates with severity of kyphoscoliosis
4) Diaphragm relatively spared until late in the disease

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What leads to kyphoscoliosis?

Weakness of paraspinal muscles

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DMD and BMD effects on the heart
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1) Dilated cardiomyopathy, cardiac hypertrophy and conduction defects all possible
2) Myocardial fibrosis
3) Sinus tachycardia
4) Ectopic rhythms (90% of patients have an abnormal ECG)
5) Cardiomyopathy more common in BMD

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Cardiomyopathy in DMD and BMD
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1) Decreased left ventricle contractility, can lead to cardiac failure
2) Often subclinical or asymptomatic
3) Often only present late in disease because of physical limitations


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Proportion of BMD and DMD patients with cardiomyopathy
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1) 1/3 in teenage years
2) 1/2 at 18 years
3) All over 18

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Most common cardiomyopathy in DMD and BMD

Dilated cardiomyopathy

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Dilated cardiomyopathy

Cardiac muscle is thin, baggy

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Orthopaedic involvement in DMD
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1) Early toe walking common
2) Contractures of Achilles' tendon, iliotibial band contractures
3) Progressive contractures of hips, knees, elbows, wrists (more problematic once wheelchair bound)
4) Scoliosis (increases in severity once wheelchair bound)

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Effects of scoliosis repair

Improves stability, but doesn't improve respiratory function

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CNS involvement in DMD
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1) Static cognitive impairment
2) Verbal performance is affected more than overall IQ (one standard deviation shift downwards, average IQ around 80)
3) No good correlation with location of deletions/duplications
4) Occasional autism

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Cognitive issues in DMD
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1) Variable cognitive impairment (1/3 have significant learning disabilities)
2) Greater difficulty manipulating verbal information, comprehension, short term memory

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Cause of DMD cognitive issues
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Multifactorial
1) Dystrophin isoform in CNS
2) School absences because of chronic illness
3) Psychosocial effects (anxiety, depression)
4) Treatment (steroids can adversely affect behaviour)
5) Parental expectations, mood problems

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Systems affected by DMD
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1) Musculoskeletal
2) Cardiac
3) Respiratory
4) Orthopaedic
5) CNS