Clinical Aspects of DMD/BMD Flashcards
What are the commonest forms of childhood muscular dystrophy?
Duchenne and Becker Muscular Dystrophy (myotonic dystrophy is the commonest cause of adult muscular dystrophy).
What is the incidence of DMD/BMD?
1 in 3,500 live male births.
DMD/BMD is usually cause by mutations in which gene?
The dystrophin gene.
Approximately what % of DMD cases are caused by large out of frame deletions that remove one or more exons?
60-65% of DMD is caused by large out of frame deletions that remove one or more exons.
Approximately what % of DMD cases are caused by exon duplication?
5% result from exon duplication.
60-65% of DMD is caused by large out of frame deletions that remove one or more exons. 5% result from exon duplication. What are the rest of the DMD cases mostly caused by?
60-65% of DMD is caused by large out of frame deletions that remove one or more exons. 5% result from exon duplication. What are the rest of the DMD cases mostly due to nonsense or frameshift mutations that cause chain termination.
What is the cause of BMD?
BMD is due to in-frame mutations that result in reduced dystrophin being produced and this can be seen by immunolabelling a muscle biopsy,
How can the reduction of dystrophin characteristic of BMD be detected?
BMD is due to in-frame mutations that result in reduced dystrophin being produced and this can be seen by immunolabelling a muscle biopsy,
Describe the clinical features of DMD.
- Onset before 5 year of age
- Developmental delay and learning difficulties (30-50%)
- Progressive muscular weakness (mainly proximal)
- Muscular pseudohypertrophy (to attempt to try and compensate for the muscle weakness) - Often will see calf hypertrophy.
- Loss of ambulation before 12 years
- Mean age of death is 25 years due to cardio myopathy and respiratory insufficiency
- Maybe at 2 yrs have very minimal symptoms which may not have been noticed - child might have bee a little bit slower walking and have more difficulty running than his peers.
- By the time the child is 8 years old they are going to have progressive weakness, particularly their pelvic girdle muscles and so that they can stand these boys tend to tilt their pelvis forward and get an increased lordosis in order for them to be able to balance. They develop an S shape when you look at them from the side.
- By 15 years likely to be in a wheelchair - will get muscle wasting and they may develop scoliosis.
Describe the classical manoeuvre seen in boys with DMD.
- When you are getting up from the floor you would generally use your pelvic muscles around your pelvic girder in order to do that. However, because they are so weak these boys have a particular manoeuvre that they use.
- What they tend to do is get themselves standing up straight with their hands on the floor and then walk their hands up their legs to get into an upright posture because they can’t pull themselves up with their hip muscles.
- This walking up the legs is called the Gower manoeuvre and is one of the classic diagnostic features that you see in DMD.
Describe the features of Becker Muscular Dystrophy.
- Becker Muscular Dystrophy is a milder condition than Duchenne.
- May be late learning to walk.
- Muscle weakness around 11 years old.
- Muscle cramps.
- Lose ability to walk around 40-50years.
- No learning difficulties.
- Survive into middle age and beyond.
Describe the features clinical features that may be seen in female muscular dystrophy carriers.
- 5-10% have cramps or mild muscle weakness.
- Usually noticed in 30’s.
- Proximal weakness and asymmetric.
- Carriers of BMD are less affected than DMD carriers.
- 20% have evidence of a dilated cardiomyopathy on investigation and women should have 5 yearly echo/EVG as adults.
How is diagnosis of DMD/BMD usually made?
- Start of with a Creatine Kinase (CK) test. Usually several thousand - extremely elevated.
- Usually the neurologist will then ask for genetic testing to try and avoid a muscle biopsy for the child. Will do a deletion/duplication analysis.
- Muscle biopsy will be done if the genetic test is negative - not just for DMD and BMD but for genetic tests in general. Will stain for dystrophin.
- At diagnosis children should have an ECG and echocardiogram to look for cardiac involvement.
Describe the management of DMD.
- Management involves physio and splinting to help prevent contractures.
- Daily steroid help to preserve ambulation.
- Complications of prednisolone need to be screened for.
- Scoliosis sometimes requires surgery.
- Nocturnal hypoventilation - facial or mask ventilation.
- Cardiomyopathy - echo and ECG every 2 years until 10 years and annually after this.
Describe the management of BMD.
- May remain ambulant or require sticks/walking frames/wheelchair.
- Should have follow up by a physiotherapist.
- Should have an echo and ECG every 5 years.
