Unit 5: Duchenne's muscular dystrophy Flashcards
What is Duchenne muscular dystrophy?
A genetic musculoskeletal disorder
Causes proximal muscle weakness and wasting
Atrophy of muscle, replaced with adipose tissue
Is a progressive and fatal condition
How does calcium ion influx cause apoptosis in a cell?
Increased level in nucleus - alters gene expression
Increased levels in mitochondria - holes in membrane, release of cytochrome C.
What are the causes of DMD mutation wise?
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.
What are the risk factors of Duchennes muscular dystrophy?
66% of cases are genetic so family history
33% spontaneous mutation - exposure to radiation or carcinogens whilst pregnant
What are the signs and symptoms of a child with DMD?
Positive Gowers sign
Hypertrophy of the calf
Loss of motor development milestones or late development milestones
Waddling gait
Proximal muscle weakness
What are the common complications of DMD?
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
Why is an EMG done for DMD?
What should it show?
Done during the identification process
Represent electrical activity in a muscle
Expect: polyphasic action potential
- reduced amplitude of clumps
- increased number of clumps
Why is an ECG done for DMD?
What should it show?
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
What role does a physiotherapist have in a DMD patient?
Encourages stretching and muscle strengthening to help slow the progression of muscle wasting
Prevent contractions and reduce pain in the patient
What is the MDT involved in a DMT patient?
Paediatrician
Cardiologist
Genetic councellor
Physiotherapist
What are the role of steroids in DMD?
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.
Why are steroids problematic in DMD?
Few teenagers comply with treatment
Many adverse reactions - such as obesity, moon face, osteoporosis, decreased fertility.
Behvaioural changes
Delayed puberty
Stomach irritation
What current genetic therapies are available for DMD?
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
What is the incidence of DMD in live birth s in the UK?
1 in 5000 live births
Most common genetic killer of boys in the UK
What might a genetic councellor do for patients with DMD and their families?
Role in diagnosis and education of family
Interpret probability of future children having a condition, or being carriers etc.
What is the most common mutation causing DMD?
Deletion of exon 45
resulting in a premture stop codon and a seveerly truncated protein
What surgical interventions may be given to a DMD patient?
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.
What lifestyle adaptations are encouraged for a DMD patient?
low calories, high protein, high fibre diet
What gait is common in DMD patients?
Lordotic posture - greater curvature in the lower spine
Walk on tip toes
Waddling
Use upper limbs to support their balance
Feet far apart
What are the common respiratory complications of DMD? why?
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
How can a blood test diagnose DMD?
Increased levels of creatine kinase, typically reaches 20,000u/l when the normal value is 35-180.
How can a quadriceps muscle needle biopsy diagnose DMD?
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
What are the main benefits of steroid treatment in DMD?
Delay muscle degeneration
Delay muscle contractures
Increase muscle strength and function
Increase pulmonary function
