Muscular dystrophy

Question 1

Most common muscular dystrophy

Answer 1

Duchenne

Question 2

Why is creatine kinase measured in boys with delayed walking?

Answer 2

Muscular dystrophy causes raised CK

Question 3

What does dystrophin do?

Answer 3

Anchors actin and prevents excessive calcium entering sarcolemma

If dystrophin is not present or faulty, calcium enters sarcolemma and water enters the mitochondria which then bursts

Oxidate stress occurs and eventually cell death occurs, muscle fibres necrose and are replaced with adipose and connective tissue

Question 4

What is Duchenne muscular dystrophy?

Answer 4

• X-linked recessive
• Presents in early childhood
• New mutations of the dystrophin gene are common meaning the female relatives of a child are not necessarily carriers

Question 5

Epidemiology of Duchenne

Answer 5

1 in 3500 new-born males

Question 6

Aetiology of Duchenne muscular dystrophy

Answer 6

• Mainly deletion mutations in dystrophin gene leading to absence or defect in the dystrophin protein causing progressive muscle degeneration
• Why does the dystrophin gene get affected so readily? Because it is a large gene
• In DMD no dystrophin is made
• In Becker’s the dystrophin is abnormal

Question 7

Presentation of Duchenne muscular dystrophy

Answer 7

Progressive proximal muscular dystrophy with pseudohypertrophy of calves

Pseudohypertrophy occurs because the muscle tissue is replaced by fat and connective tissue

• All patients symptomatic by age 3
• Delayed motor milestones
• Cant run
• Waddling gait
• Gower’s sign – climbing up legs
• Speech delay
• FTT
• Abnormal LFTs
• Fatigue
• Malignant hyperthermia/ other anaesthetic complications

Question 8

Investigations for Duchenne muscular dystrophy

Answer 8

Initial investigation is serum CK: In DMD the level is very high (10-100x normal)

Normal CK at presentation excludes DMD - CK eventually falls later on in the disease as muscle wasting occurs so it is not a reliable screening test for those already in wheelchairs

Precise diagnosis via:

• Genetic analysis
• Muscle biopsy
• Clinical observation of muscle strength and function

Serum CK is usually high in carriers

Question 9

Differentials for Duchenne muscular dystrophy

Answer 9

• Becker’s
• Other myopathies
• Polymyositis
• Spinal cord lesions

Question 10

Management of Duchenne

Answer 10

Physio to prevent contractures

Knee-foot-ankle orthoses to help prolong walking

Serial casting of ankles

Corticosteroids

• May improve muscle strength and function in the short term but balance this against risk of osteoporosis

Question 11

Management of Duchenne after walking ability lost

Answer 11

• Independent mobility lost around age 8-11
• Wheelchairs
• Orthotics or surgery for contractures and scoliosis
• Cardiac and respiratory surveillance
• Support and adaptations for school
• Counselling

Question 12

Management of Duchenne in the later stages

Answer 12

• Support for increasing weakness and fatigue
• Optimise cardiac and respiratory treatment
• Respite for family
• Palliative care

Question 13

Complications of Duchenne

Answer 13

• Joint contractures
• Respiratory complications
• Respiratory failure is the most common cause of death
• Cardiac complications, dilated cardiomyopathy is common
• Gastro: pseudo obstruction
• Learning difficulty 20%
• Anaesthetic complications

Question 14

Prognosis of Duchenne muscular dystrophy

Answer 14

• Hand muscles and extraocular muscles spared until late on
• Affected boys usually confined to wheelchair by age 12
• Death from respiratory complications in 20s or 30s

Question 15

Risks for female carriers of DMD mutation

Answer 15

Increased risk of cardiomyopathy

• 10% lifetime risk

Manifesting carriers: 2-5% have skeletal muscle symptoms

• Aches, calf muscle enlargement, symptoms tend to progress with time

Question 16

What is Becker’s muscuar dystrophy?

Answer 16

Epidemiology

• 1 in 17,000 liver births (1/5 of that of DMD)

Aetiology

• Due to abnormalities of the dystrophin gene - partly-functional dystrophin is produced
• X-linked recessive

Question 17

Presentation of Becker’s mucsular dystrophy

Answer 17

• Symptoms begin in early childhood
• Average age at diagnosis is 11
• Delayed walking
• Muscle cramps on exercise
• Struggling with school sports
• Muscle weakness affecting proximal muscles
• Usually occurs in teenage years - 20s e.g. trouble climbing stairs or lifting heavy objects
• Patients can usually walk until the age of 16
• Walking ability usually lost age 20-30

Question 18

Signs of Becker’s muscular dystrophy

Answer 18

• Myoglobinuria
• Anaesthetic complications
• Cardiomyopathy
• Higher incidence of learning difficulties

Question 19

Investigations for Becker’s

Answer 19

• CK in serum shows moderate increase (5-50x normal)
• Genetic analysis
• Muscle biopsy
• Monitoring for cardiomyopathy

Question 20

Management of Becker’s muscular dystrophy

Answer 20

Supportive

• Exercise programmes
• Physio
• Optimise nutrition
• Walking ability lost: walking aids/ wheelchair
• Psychological support

Cardiac

• Dilated cardiomyopathy occurs in most BMD patients – is sometimes the presenting symptom and is the main factor influencing survival
• Regular cardiac monitoring from diagnosis
• ECG and echo may be difficult to interpret because of scoliosis
• ACEi, b-Blockers, diuretics for heart failure

Question 21

Prognosis of Becker’s

Answer 21

• Life expectancy is often reduced but there is a wide variation in severity so prognosis can vary
• Cardiomyopathy is the cause of death in 50%

Question 22

What is myotonic dystrophy?

Answer 22

Multi-system inherited (Autosomal dominant) disorder characterised by myotonia (failure of voluntary muscle relaxation following contraction), & various other complications.