Unit 5: Duchenne's muscular dystrophy

Question 1

What is Duchenne muscular dystrophy?

Answer 1

A genetic musculoskeletal disorder
Causes proximal muscle weakness and wasting
Atrophy of muscle, replaced with adipose tissue
Is a progressive and fatal condition

Question 2

How does calcium ion influx cause apoptosis in a cell?

Answer 2

Increased level in nucleus - alters gene expression
Increased levels in mitochondria - holes in membrane, release of cytochrome C.

Question 3

What are the causes of DMD mutation wise?

Answer 3

Mutation in the dystrophen gene, resulting in a severly truncated or absent dytrophen protein
Z disk is not anchored to sarcolemma/endomysium, is damaged as used, resulting in necrosis and atrophy.
Key parts of the dystropehn glycoportein complex: dystrophen links actin to sarcomere, sarcoglycan in sarcomere, laminin links to endomysium.
When broken muscle does not contract as a whole, holes in sarcolemme, calcium ion influx causes apoptosis, release creatine kinase as a sign of muscle damage.

Question 4

What are the risk factors of Duchennes muscular dystrophy?

Answer 4

66% of cases are genetic so family history
33% spontaneous mutation - exposure to radiation or carcinogens whilst pregnant

Question 5

What are the signs and symptoms of a child with DMD?

Answer 5

Positive Gowers sign
Hypertrophy of the calf
Loss of motor development milestones or late development milestones
Waddling gait
Proximal muscle weakness

Question 6

What are the common complications of DMD?

Answer 6

By age 12 require a wheelchair
By 20s require ventilation at night
By 30s require 24/7 ventilation
Death in late 30s by respiratory or cardiac abnormalities
Respiratory - pneumonia, unable to cough, airway collapse as tracheal muscle wasts
Cardiac - arrythmias, embolisms, decreased cardiac output, heart failure

Question 7

Why is an EMG done for DMD?
What should it show?

Answer 7

Done during the identification process
Represent electrical activity in a muscle
Expect: polyphasic action potential
- reduced amplitude of clumps
- increased number of clumps

Question 8

Why is an ECG done for DMD?
What should it show?

Answer 8

Typically done in later stages
identify the developement of cardiac abnormalities
May be alongside an echocardiogram - size, shape of heart walls and valves
Identify the functioning of cardiac muscle

Question 9

What role does a physiotherapist have in a DMD patient?

Answer 9

Encourages stretching and muscle strengthening to help slow the progression of muscle wasting
Prevent contractions and reduce pain in the patient

Question 10

What is the MDT involved in a DMT patient?

Answer 10

Paediatrician
Cardiologist
Genetic councellor
Physiotherapist

Question 11

What are the role of steroids in DMD?

Answer 11

Prednisolone - 1st line treatment - is a glucocorticoid
Deflaxacourt - glucocorticoid - newly FDA approved.
Encourage muscle growth.
Often given between ages four and six

Previously used anabolic steroids - more dangerous side effects - used for muscle growth by body builders.

Question 12

Why are steroids problematic in DMD?

Answer 12

Few teenagers comply with treatment
Many adverse reactions - such as obesity, moon face, osteoporosis, decreased fertility.
Behvaioural changes
Delayed puberty
Stomach irritation

Question 13

What current genetic therapies are available for DMD?

Answer 13

Antisense oligonucleotides - induce exon skipping
Mutation specific - exon 45, exon 51 and exon 53
Typically change from Duchennes to Beckers

Ataluren - ignores premature stop codond
Etiplersen - exon 51 skipping

Question 14

What is the incidence of DMD in live birth s in the UK?

Answer 14

1 in 5000 live births
Most common genetic killer of boys in the UK

Question 15

What might a genetic councellor do for patients with DMD and their families?

Answer 15

Role in diagnosis and education of family
Interpret probability of future children having a condition, or being carriers etc.

Question 16

What is the most common mutation causing DMD?

Answer 16

Deletion of exon 45
resulting in a premture stop codon and a seveerly truncated protein

Question 17

What surgical interventions may be given to a DMD patient?

Answer 17

Spine surgery to prevent scoliosis
Limb contractions - to prevent permanent flexion of limbs
Heel cold surgery to lengthen the achilles tendon can prolong standing and walking.

Question 18

What lifestyle adaptations are encouraged for a DMD patient?

Answer 18

low calories, high protein, high fibre diet

Question 19

What gait is common in DMD patients?

Answer 19

Lordotic posture - greater curvature in the lower spine
Walk on tip toes
Waddling
Use upper limbs to support their balance
Feet far apart

Question 20

What are the common respiratory complications of DMD? why?

Answer 20

Infection often pneumonia - ineffective cough reflex
Diaphragm pseudohypertrophy - reduced tidal volume and reduced lung wall compliance, leads to hypoventilation, hypoxia and hypercapnia.
Often requires ventilation

Question 21

How can a blood test diagnose DMD?

Answer 21

Increased levels of creatine kinase, typically reaches 20,000u/l when the normal value is 35-180.

Question 22

How can a quadriceps muscle needle biopsy diagnose DMD?

Answer 22

Histological changes in muscle
Loss of muscle fibres - replaced by white adipose tissue
Odema - white water filled spaces
Increased connective tissue
Remaining muscle fibres are smaller and vary in shape and size
Develop internalised nuclei.
May also be tested for the presence of dystrophen by immunohistochemistry

Question 23

What are the main benefits of steroid treatment in DMD?

Answer 23

Delay muscle degeneration
Delay muscle contractures
Increase muscle strength and function
Increase pulmonary function