Muscular dystrophy/SMA

Question 1

Duchenne muscular dystrophy - background

Answer 1

1. X-linked recessive condition that lies at the severe end of the spectrum of disorders (typically affects boys). Due to a molecular abnormality of dystrophin
2. Classically presents within the first 4y
3. Delayed motor milestones and mild speech delay

Question 2

DMD - presentation

Answer 2

1. Typically present with waddling gait and/or language delay. Having to mount stairs one by one; running slowly compared to peers
2. Average age of dx 5.5y, but children often become symptomatic much earlier
3. Progressive muscle atrophy + weakness -> no longer ambulant by 10-14y. Scoliosis is a common complication
4. 1/3 of affected children have learning difficulties
5. Life expectancy reduced to late twenties from respiratory failure or the associated cardiomyopathy

Question 3

DMD - ex

Answer 3

1. Waddling lordotic gait
2. Pseudohypertrophy of the calves due to replacement of muscle fibres by fat and fibrous tissue
3. Weakness in limb girdles (lower more than upper) -> Gower’s sign (the need to turn prone to rise)
4. Scoliosis (a common complication)
5. Sparing of facial, extra-ocular and bulbar muscles

Question 4

DMD - ix (2)

Answer 4

1. Markedly raised creatine kinase
2. Genetic analysis - this does not differentiate between the milder Becker muscular dystrophy and more severe DMD. Expert interpretation is required
   …?

Question 5

DMD - mx

Answer 5

1. Appropriate exercise = helps to maintain muscle power and mobility. Delays the onset of scoliosis
2. Contractures (esp ankles) should be prevented by passive stretching and provision of night splints. Walking can be prolonged with the provision of orthoses. Ambulant children increasingly treated with corticosteroids (prednisolone for 10d each mo), but precise mechanism of action not known
3. Maintain good sitting posture to minimise the risk of scoliosis. Manage scoliosis with a truncal brace, moulded seat and ultimately surgical insertion of a metal spinal rod
4. Later in the condition:
   - Respiratory aids (esp. overnight CPAP or non-invasive positive pressure ventilation [NIPPV])
5. Parent self-help groups = source of information + support. Affected children should be periodically reviewed at a specialist regional centre

Question 6

Muscular dystrophies - overview

Answer 6

A group of congenital disorders that are characterised by dystrophic change on muscle biopsy. Can affect muscles in different patterns and are characteristically associated with a raised creatine kinase enzyme

1. DMD
2. BMD
3. Congenital muscular dystrophies (heterogenous group of disorders)

Question 7

SMA - overview + clinical picture

Answer 7

SMA = spinal muscular atrophy

1. Autosomal recessive degeneration of anterior horn cells. Second most common cause of neuromuscular disease after DMD
2. Leads to progressive weakness and wasting of skeletal muscles due to mutations in the survival motor neurone (SMN) gene. Development of symmetrical proximal muscle weakness as a consequence of degeneration of the anterior horn cells of the spinal cord. Intelligence unaffected
3. Severe cases = babies feed normally for first few weeks with the earliest sign often being of a tiring infant who does not finish their feed. Clinical examination may show fasciculations of the tongue (important clinical indicator)
4. Several types:
   a. Type 1 (severe) = onset in first few months of life, never able to sit or walk, usually die from respiratory failure by 6-12mo
   b. Type 2 (intermediate) = onset before 18mo, able to sit but not to walk unaided, survival into adult life usual
   c. Type 3 (mild) = onset of proximal muscle weakness after 2y, able to walk independently; survival into adult life
5. Dx = made by molecular genetic testing
   Mx = ?