[41] Duchennes Muscular Dystrophy Flashcards
What is Duchennes muscular dystrophy (DMD)?
A severe type of muscular dystrophy
What are muscular dystrophies?
A group of muscle diseases that result in increased weakening and breakdown of skeletal muscle over time
What is the incidence of DMD?
It affects 1 in 3000-6000 male infants
What is the life expectancy of patients with DMD?
Late 20’s
What is the cause of death in most causes of DMD?
- Respiratory failure
- Associated cardiomyopathy
What is the inheritance pattern of DMD?
X-linked recessive, although about 1/3 have de novo mutations
What is the genetic abnormality in DMD?
Deletion of the gene for dystrophin
What is the role of dystrophin?
It connects the cytoskeleton of a muscle fibre to the surrounding extracellular matrix through the cell membrane
What happens when dystrophin is deficient?
There is an influx of calcium ions, a breakdown of the calcium calmodulin, and an excess of free radicals, ultimately leading to myofibre necrosis
What is the average age of diagnosis of DMD?
5 years old (but children often become symptomatic much earlier than this)
What are the clinical features of DMD?
- Waddling gait
- Language delay
- Gowers sign
- Pseudohypertrophy of calves
- Slower and clumsier than peers
What is Gowers sign?
The need to turn prone to rise
What causes pseudohypertrophy of the calves in DMD?
Replacement of muscle fibres by fat and fibrous tissue
How does DMD progress?
Progressive muscular atrophy and weakness, so no longer ambulant by 10-14 years
How common are learning difficulties in DMD?
About 1/3 of affected children have learning difficulties
How can DMD be detected on neonatal screening?
Elevated CK
What is the initial investigation for suspected DMD?
CK
What is found on CK testing in DMD?
CK level 10-100x
Is CK high from birth in DMD?
Yes
Does a normal CK at presentation exclude DMD?
Yes
How is a precise diagnosis of DMD best achieved?
By a combination of;
- Genetic analysis
- Muscle biopsy, with assay for dystrophin protein
- Clinical observation of muscle strength a function
What are the differential diagnoses for DMD?
- Other types of muscular dystrophy, particularly Becker’s muscular dystrophy
- Other myopathies
- Polymyositis
- Neurological causes of muscle weakness
Give an example of a neurological cause of muscle weakness
Spinal muscular atrophy
What does the initial management of DMD include?
- Information and support for family
- Genetic diagnosis and counselling
- Referral to specialist and MDT
What does early-stage management when the child is walking include in DMD?
- Physiotherapy
- Knee-foot-ankle orthoses
- Corticosteroids
What is the purpose of physiotherapy in early-stage management of DMD?
To give advice on stretching to prevent contractures
What is the purpose of knee-foot-ankle orthoses in early-stage management of DMD?
To prolong walking
What is the purpose of corticosteroids in early-stage management of DMD?
- Prolong ambulation by 6-12 months
- Help with respiratory function, cardiomyopathy, and scoliosis
What is the usual steroid giving in DMD?
Prednisolone
What is involved in management after walking is lost in DMD?
- Help with mobility, usually with electric wheelchair
- Cardiac and respiratory surveillance
- Orthopaedic care
What is involved in management in the later stages of DMD?
- Support for increasing weakness and fatigue
- Optimisation of respiratory and cardiac treatments
- Nutritional advice
- Palliative care
What might be required to provide support for increasing weakness and fatigue in the later stages of DMD?
Wheelchair and other living adaptations
What research is going into the treatment for DMD?
Into exon skipping drugs
What do exon skipping drugs do in DMD?
May correct the open reading frame of the dystrophin gene
Give an example of an exon skipping drug in DMD
Ataluren
Who is ataluren used for in DMD?
Patients with a nonsense (skip) mutation
What % of cases of DMD have a nonsense mutation?
10-15%
What does ataluren do?
Allows bypass of the nonsense mutation and a production of a small amount of dystrophin
What are the potential complications of DMD?
- Scoliosis
- Respiratory complications
- Cardiac complications
- Gastrointestinal symptoms
What respiratory complications may arise from DMD?
Weakness of intercostal muscles
What might weakness of intercostal muscles lead to?
Noctural hypoxia
How does noctural hypoxia present?
- Daytime headache
- Irritability
- Loss of appetite
How can noctural hypoxia in DMD be managed to improve quality of life?
Overnight CPAP or non-invasive positive pressure ventilation
What cardiac complications may arise from DMD?
- Dilated cardiomyopathy
- Arrhythmias
What causes gastrointestinal symptoms in DMD?
Smooth muscle being affected
What gastrointestinal symptoms may result from DMD?
- Gastric dilation
- Pseudo-obstruction
