Flashcards in Lecture 33 - Muscular Dystrophies - Clinical Aspects Deck (43):
List some dystrophinopathies
• Duchenne muscular dystrophy
• Becker muscular dystrophy
Be aware of these others:
• Familial cramps + myalgia syndrome
• X-linked dilated cardiomyopathy
• Isolated elevated CK
• Manifesting carrier females
• Isolated quadriceps myopathy
All due to mutation in dystrophin of some sort
Compare the following in DMD and BMD:
• Age of onset
• Age of diagnosis
• Wheelchair dependency
Age of onset:
• DMD: 5
• DMD: 1/3500
• BMD: 1/35000
Age of diagnosis
• DMD: 2-4 years
• BMD: variable
• DMD: 12
• BMD: not before 16, if ever
To where does the Dystrophin gene map?
List the clinical presentations of DMD
• Delayed motor milestones
- Mean age of walking is 18 months (normally t lift head when lying on the end of a bed
• Gait difficulties
• Fatigability, clumsiness
• Speech delay
When do children usually start to walk?
Before the age of 18 months
In DMD, the average age of walking is 18 months
In DMD, which muscles are seen to be hypertrophied?
Which muscles are spared?
Characterise the hypertrophy
• Even tongue
• Facial muscles
• Extra-ocular muscles
• Excess fat and connective tissue
Describe Gowers' sign
Of what is it indicative?
Boy lying on back on the ground
Asked to stand up
1. Roll onto their stomach
2. Crouch on all fours, push up on arms
3. Hands walk up legs
This is not the normal way to stand up
An important neurological sign
Provides a mechanical advantage if there is proximal weakness around the pelvic girdle
• Indicates proximal weakness in limb girdle (hip)
• Only considered pathological and indicative of proximal weakness after the age of four
• This is normal in children younger than three
• It is also seen in other muscle disorders
Describe the feature of muscle atrophy
Just important to remember that muscles can be thinned as well as hypertrophied
Describe the process of diagnosis of DMD
-- Screening --
1. Serum Creatine Kinase level
• Normal: 10 000 IU/L
• Degeneration of muscle, leakage of CK into the serum
2. Thyroid function tests
• Hypothyroidism can look like DMD
• Need to exclude this
-- Genetic testing --
• True positive in 65-70% of cases (i.e. of boys with DMD)
• Deletions: 65%
• Duplications: 5%
• Point mutations: 10-15%
4. Muscle biopsy
• Genetic tests were negative, but there is great suspicion of DMD
• Gold standard
• Histological tests performed
In what proportion of cases is muscle biopsy required?
Describe the possible results of the serum CK test
There are lots of things that could cause abnormal (or normal) CK
Elevated CK does not mean that it is a muscle problem
1. Normal: less than 200 IU/L
2. Mildly elevated: 200-1000
3. Elevated: more than 1000 IU/L
• DMD (>10 000)
• FSH MD
Describe the natural history of DMD
3-6 years: Honeymoon phase
• Still ongoing gains in strength
• But not at the same rate as other healthy children
• Gower sign
• Calf pseudohypertrophy
8 years: marked functional difficulties
• Increasing muscle weakness and fatigability
• Increasingly prominent lumbar lordosis
• Progressive contractures
• Loss of ambulation - transition to wheelchair
• Progessive scoliosis
• Progressive respiratory deficit
Late teens, early 20's: Death
• Due to respiratory or cardiac failure
What is the average age of death in DMD?
Death average approx. 25 years
What is death usually due to in DMD?
Respiratory failure (90%)
Cardiac failure (10%)
What are contractures?
Joint fixed in a position of flexion, unable to be extended
Describe the natural history of BMD
Can be quite variable
• Commonly 5-15
• Can be as late as 20-30
• Limb girdle weakness
• Definitely no wheelchair before 15
• Calf pain and myalgias
• After 30, generally
• Cardiomyopathy, respiratory failure
In which congenital MD is cardiomyopathy more common?
Describe the effect of DMD on the respiratory system
Restrictive deficit due to:
Weakness of intercostal muscles (and diaphragm, to a lesser extent)
• Early years: increases with age and growth
• In early teens: plateaus and then declines steadily (5-10% / year)
• Usually in the late teens or early 20s
If there are weak respiratory muscles, what is the first clinical sign?
1. Sleep-disordered breathing
• Poor exercise tolerance
• Poor school performance
• Hypercapnia (CO2 retention)
• Not hypoxia
2. Nocturnal hypoventilation
3. Daytime hypoventilation
What sort of lung disease does muscle weakness cause?
Restrictive lung disease
Compare restrictive and obstructive lung disease
• Reduced expansion of lung parenchyma
• Decreased total lung capacity
• Due to muscle weakness
• Also seen when there is fibrosis and restriction of lung movement
• FEV uncharged
• Increased resistance in airway
• e.g. Asthma
• Decrease maximal airflow rates in lung function tests, i.e. decreased FEV1
What is Atelectasis?
What causes it?
Collapse of lung parenchyma
Caused by poor aeration of lungs
Describe what is seen in advanced DMD respiratory deficit
• Progression to nocturnal / daytime hypoventilation
Scoliosis compounds this
Describe scoliosis in DMD
What causes it?
Due to imbalance of paraspinal muscles
Curves depending on which side is weaker/stronger
Describe cardiac involvement in DMD and BMD
Which disorders are seen?
What are the sequelae?
In order of prevalence:
1. Dilated cardiomyopathy
3. Conduction deficits
• Decreased left ventricular contractility
• Occasional cardiac failure
• Doesn't pump properly
• Commonly asymptomatic / subclinical (because kids aren't really exercising)
• Abnormal electrical activity of the heart
• Less common
• Myocardial fibrosis
• Sinus tachycardia (Heart must beat faster to compensate)
• Ectopic rhythms
Compare the two types of cardiomyopathy
Which is more common in DMD?
• Cardiac muscle floppy and baggy
• More common in DMD
• Muscle is thickened
• Less common in DMD, but still observed
Describe the orthopaedic involvement in DMD
• Achilles and iliotibial band→ toe walking
• Increases rapidly after non-ambulant
• Sitting, slumped to one side → scoliosis
3. Lumbar lordosis
Describe the CNS involvement in DMD
Is is static or progressive?
Which disorders are sometimes seen in DMD?
Static cognitive impairment
• Affects verbal (rather than performance) IQ
• Mean IQ curve shifted one standard deviation to the left
• Following verbal instructions
• Comprehension of verbal information
• Memory storage of verbal information
Two major types:
• Reduced verbal IQ
• Reduced total IQ (<80)
How common is cognitive involvement in DMD?
About 1/3rd affected
Describe the cause of cognitive problems in DMD
1. Altered dystrophin expression in brain
• Behavioural changes
3. Psychosocial effects
• Behavioural problems (steroids)
4. Effect on family
• Parental expectations
• Parental mood problems
5. Effect of chronic illness
• School absences
• Visits to hospital and doctors
Which muscles are spared in DMD?
• Extra-ocular muscles
• Facial muscles (usually)
Describe muscle disorder in DMD
• Weak neck flexors
• Weak limb girdle (hip, shoulder)
• Weak trunk muscles
Hypotonia (floppy baby)
What is the difference between cardiac arrhythmias and cardiomyopathy?
Cardiomyopathy: structural problems
Arrhythmias: irregular electrical activity of the heart
When is ambulation usually lost in DMD?
Anywhere between 8-14 years
Definitely by 15
In all neuromuscular disorders, respiratory muscle function is worst during ...
There is decreased muscle tone and central drive at this time
Leads to SDB
What is SDB?
Sleep disordered breathing
When is SDB the worst?
During REM sleep
What is the interaction between scoliosis and respiratory function?
Increased scoliosis → increased loss of respiratory reserve
When is cardiomyopathy seen in DMD and BMD?
18 years: ½
>18 years: all
What percent of deaths does cardiac failure account for in DMD?
What is sinus tachycardia?
Heart beats faster to compensate
When does scoliosis occur in DMD?
Increases rapidly once boy is non-ambulant