Lecture 33 - Muscular Dystrophies - Clinical Aspects Flashcards
List some dystrophinopathies
- Duchenne muscular dystrophy
- Becker muscular dystrophy
Be aware of these others:
• Familial cramps + myalgia syndrome
Others: • 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 • Incidence • Age of diagnosis • Wheelchair dependency
Age of onset:
• DMD: 5
Incidence
• DMD: 1/3500
• BMD: 1/35000
Age of diagnosis
• DMD: 2-4 years
• BMD: variable
Wheelchair dependency
• DMD: 12
• BMD: not before 16, if ever
To where does the Dystrophin gene map?
Xp21
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
• Calves Also: • Quads • Gluteals • Deltoid • Even tongue
Not affected:
• Facial muscles
• Extra-ocular muscles
Early hypertrophy
Late pseudohypertrophy:
• Excess fat and connective tissue
Describe Gowers’ sign
Of what is it indicative?
Boy lying on back on the ground
Asked to stand up
Child will:
- Roll onto their stomach
- Crouch on all fours, push up on arms
- 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
Indication:
• 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 –
- Serum Creatine Kinase level
• Normal: 10 000 IU/L
• Degeneration of muscle, leakage of CK into the serum - Thyroid function tests
• Hypothyroidism can look like DMD
• Need to exclude this
– Genetic testing –
3. MLPA • True positive in 65-70% of cases (i.e. of boys with DMD) • Deletions: 65% • Duplications: 5% • Point mutations: 10-15%
- 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?
1/3rd
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
- Normal: less than 200 IU/L
• DM1 - Mildly elevated: 200-1000
3. Elevated: more than 1000 IU/L • DMD (>10 000) • BMD • LGMD • 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
10-13 years:
• 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%)
• Cardiomyopathy
• Arrhythmias
What are contractures?
Joint fixed in a position of flexion, unable to be extended
Describe the natural history of BMD
Can be quite variable
Clinical onset:
• Commonly 5-15
• Can be as late as 20-30
Progression • Limb girdle weakness • Cardiomyopathy • Definitely no wheelchair before 15 • Calf pain and myalgias
Death
• After 30, generally
• Cardiomyopathy, respiratory failure
In which congenital MD is cardiomyopathy more common?
BMD
