Muscular dystrophy

Question 1

Define muscular dystrophies and give examples

Answer 1

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

Question 2

What is the aetiology of Duchenne Muscular dystrophy

Answer 2

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

Question 3

What is the epidemiology of Duchenne Muscular Dystrophy (DMD)

Answer 3

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

Question 4

What are the symptoms and signs of Duchenne muscular dystrophy

Answer 4

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

Question 5

What investigations should be done for Duchenne muscular dystrophy

Answer 5

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

Question 6

What is the management for Duchenne Muscular Dystrophy

Answer 6

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

Question 7

What are the complications of Duchenne muscular dystrophy

Answer 7

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

Question 8

What is the prognosis for Duchenne Muscular dystrophy

Answer 8

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

Question 9

What is the aetiology of Becker muscular dystrophy

Answer 9

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

Question 10

What are the signs and symptoms of Becker muscular dystrophy

Answer 10

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

Question 11

What is the prognosis for Becker muscular dystrophy

Answer 11

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

Question 12

Describe limb girdle muscular dystrophies

Answer 12

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

Question 13

Describe congenital muscular dystrophies

Answer 13

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

Question 14

What are the signs and symptoms of congenital muscular dystrophies

Answer 14

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

Question 15

What is the aetiology of myotonic dystrophy

Answer 15

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)

Question 16

What are the signs and symptoms of myotonic dystrophy

Answer 16

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

Question 17

What are myotonic facies

Answer 17

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

Question 18

What investigations should be done for myotonic dystrophy

Answer 18

CK: elevated
genetic testing

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

Question 19

What is the management for myotonic dystrophy

Answer 19

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

Question 20

What are the complications of myotonic dystrophy

Answer 20

Joint contractures
Foot deformities
Early-onset dementia

Question 21

What is the prognosis for myotonic dystrophy

Answer 21

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