Muscular dystrophy Flashcards

1
Q

Define muscular dystrophies and give examples

A

Group of inherited disorders with progressive muscle degeneration, characterised by muscle weakness and wasting of variable distribution and severity

Duchenne muscular dystrophy
Becker muscular dystrophy
Limb girdle muscular dystrophies
Congenital muscular dystrophies

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2
Q

What is the aetiology of Duchenne Muscular dystrophy

A

X-linked recessive disorder - Xp21 gene mutation
1/3 boys have de novo mutations
Deletion of the gene for dystrophin (connects the cytoskeleton of a muscle fibre to the surrounding extracellular matrix through the cell membrane)
Deficient dystrophin → calcium ion influx → breakdown of calcium calmodulin complex → excess free radicals → progressive myofibre necrosis

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3
Q

What is the epidemiology of Duchenne Muscular Dystrophy (DMD)

A

Affects 1 in 3000-6000 male infants
Most common muscular dystrophy
Average age of diagnosis = 5yo (but S/S start earlier)

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4
Q

What are the symptoms and signs of Duchenne muscular dystrophy

A

Waddling gait
Toe-walking
Language delay
Mounting stairs one by one
Run slowly compared to peers
Slower and clumsier than peers
No longer able to walk by 10-14 years old (due to the progressive muscle atrophy and weakness)
Gower’s sign (need to turn prone in order to rise >3yo)
Pseudohypertrophy of the calves (replacement of muscle by fat and fibrous tissue

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5
Q

What investigations should be done for Duchenne muscular dystrophy

A

Bloods: Creatine kinase (CK) = elevated
Other:
- EMG: Establishes myopathic nature, exclude neurogenic causes of muscle weakness
- Muscle biopsy: immunostaining for dystrophin
- Lung function testing: reduced muscle strength → decreased vital capacity

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6
Q

What is the management for Duchenne Muscular Dystrophy

A

MDT management
OT/PT: moderate physical exercise, mobility aids, night splints, spinal support
Corticosteroids
Atluren (allows bypass of the mutation and production of a small amount of dystrophin
Education
Psychological support and counselling
Genetic counselling

Systemic support
Early and aggressive cardiomyopathy management
Respiratory care and assisted respiration
Immunisation (pneumococcal, influenza)
Prophylactic Abx
Orthopaedic: tendoachilles lengthening, scoliosis surgery
OSA → overnight CPAP

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7
Q

What are the complications of Duchenne muscular dystrophy

A

Respiratory failure
Cardiomyopathy → cardiac failure
Loss of mobility
Learning difficulties
Scoliosis
OSA
Weight loss/malnutrition
Osteoporosis, vertebral compression fractures
Sexual dysfunction

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8
Q

What is the prognosis for Duchenne Muscular dystrophy

A

Often not walking by 10-14yo
- 10yo: needs braces to walk
- 12yo: most are wheelchair-bound
Life expectancy reduced to the late twenties from respiratory failure or cardiomyopathy

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9
Q

What is the aetiology of Becker muscular dystrophy

A

Allelic with Duchenne muscular dystrophy (different mutations, same gene)
Some functional dystrophin is produced (30-80% normal)
Exon deletions exist in the dystrophin gene Xp21 in 70% cases

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10
Q

What are the signs and symptoms of Becker muscular dystrophy

A

Similar to Duchenne muscular dystrophy, but milder and progresses more slowly
Average age of onset = 11yo

Learns to walk later than usual
Muscle cramps after exercise
Struggles with sports at school
Struggling with lifting objects

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11
Q

What is the prognosis for Becker muscular dystrophy

A

Loss of independent ambulation in the late 20s
Life expectancy well into middle or old age

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12
Q

Describe limb girdle muscular dystrophies

A

Proximal upper and lower limb weakness
Cardiomyopathy and difficulty with breathing
Plasma CK raised

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13
Q

Describe congenital muscular dystrophies

A

Autosomal recessive inheritance
Presents at birth or early infancy
Muscle biopsy: dystrophic features with reduction of one of the extracellular matrix proteins e.g. laminin

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14
Q

What are the signs and symptoms of congenital muscular dystrophies

A

Presents at birth or early infancy
Proximal weakness, slowly progressive
Hypotonia
Contractures (contracture when the ability to walk is lost)
Feeding difficulties
Breathing difficulties
Intellectual disability

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15
Q

What is the aetiology of myotonic dystrophy

A

Autosomal dominant
Most common adult-onset muscular dystrophy (20-30s)
Expansion of CTG nucleotide triplet on the DMPK gene (Chr19)
Holds genetic anticipation (earlier onset in offspring)

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16
Q

What are the signs and symptoms of myotonic dystrophy

A

Perinatal: oligohydramnios, reduced foetal movements
Infants: hypotonia, feeding difficulties, resp. difficulties, talipes
Children:
- Myotonic facial appearance
- Learning difficulties
- Myotonia, hypotonia
- Progressive muscle loss and weakness (smaller > larger)
- Thin ribs

Adults: cataracts, blindness, testicular atrophy, T2DM, slow release of handshake, difficulty releasing a tightly clasped fist, cardiac arrhythmia

17
Q

What are myotonic facies

A

Bilateral ptosis
Wasting of frontalis and temporalis muscles
Weakness of sternomastoids
Lack of facial expression

18
Q

What investigations should be done for myotonic dystrophy

A

CK: elevated
genetic testing

EMG: “Dive bomber” sound spontaneous electrical discharge
Muscle biopsy: immunostaining
Lung function testing

19
Q

What is the management for myotonic dystrophy

A

MDT
Physiotherapy: strength and flexibility training
SALT: difficulty swallowing, dysarthria
OT: utensils, wrist braces
Orthopaedic: management for foot-drop
Genetic counselling/antenatal diagnosis
Psychological support

Medications: quinine, procainamide (support resp. GI problems)
Surgical: cataract operations

20
Q

What are the complications of myotonic dystrophy

A

Joint contractures
Foot deformities
Early-onset dementia

21
Q

What is the prognosis for myotonic dystrophy

A

Death occurs due to cardiac conduction defects
Depends on number of CTG repeats
Learning disability extent can be improved by early MDT involvement
The older the child is when muscle weakness is noticed, the slower the progression and less serious the consequences
Most do nots survive past 50 years