Duchennes Muscular Dystrophy Flashcards
Give an overview of DMD
Epidemiology and course of disease
Most common genetic mutation in children
Affects 2500 boys in the UK
Each year 100 boys are diagnosed with DMD
Causes progressive muscle weekness due to lack of dystrophen
wheelchair bound by teens, ventilation needed by twenties
What do the figures show about people who are affected by DMD?
Affects 1 in 5,000 male births
33% spontaneous, 66% are inherited
Is the largest genetic killer of boys, avergae life span is 25yrs with most deaths by heart or lung failure
Often diagnoses between the ages of 3-5yrs
30% of affected children are also on the autism spectrum
Give an overview of the dystrophen gene.
Mutation impairs production of dystrophin protein in muscles
Consists of 79 axons, one of the longest genes
Located on Xp21.2
What are the consequences of a lack of dystrophen?
Without Dystrophin muscle becomes fibrosed, is replaced by fat and eventually breaks down.
Dystrophen indirectly anchors actin filaments to the sarcomere and endomysium, this provides stability to the muscle fibre and ensures the whole muscle shortens during contraction, providing strength.
Part of the dystrophen glycoprotein complex
What is the difference between Beckers MD and Dystrophen MD?
A mutation that breaks the reading frame, meaning no dystrophen causes the more severe symptoms of DMD. This is also known as an out of frame mutation. Life expectancy is around 25-30yrs
A mutation that does not break the reading frame only changes it causes the less severe symptoms of DMD, as some Dystrophin is produces it is just not fully functional.This is also known as an in frame mutation. Increases life expectancy to 40-50 years
How does the histological image change between healthy muscle and muscle in DMD?
Muscle fibres becomes smaller and less regular in arrangement.
White spaces are apparent between muscle fibres, caused by odema.
Eventually muscle is replaced by white adipose tissue
What are some typical presenting features of toddlers with DMD?
Delayed motor milestones
Poor head Control
Frequent Falling
Waddling gait
What are some typical presenting features of school age children with DMD?
Difficulty climbing steps
Waddling gait
Difficulty jumping and running
Gowers sign
What are some features associated with DMD?
Speech delays
Behavioural difficulties
Calf hypertrophy.
What are some features of a child with DMD walk?
Shoulders and arms are held awkwardly
Belly sticks out due to week muscles also helps give momentum to pull the child forward
Falls often
Walks on the tips of their toes
Lordosis - great curvature of the spine, showed by inward curvature of the lower back.
Feet at shoulder width apart.
How does DMD typically progress over time?
Walking problems develop from age 2-3yrs
Wheel chair bound by highschool, often before 12yrs
Very limited use of arms before age 15yrs
Ventilation at night by age 17yrs
Ventilation every 24hrs by age 20yrs
Death by 25-30yrs.
What is used as a diagnositic tool for DMD?
Clinical: Gowers sign
Blood test: Creatine kinase elevated in 1000s, deranges liver enzymes
DNA analysis to look for mutation and affected axon
Muscle biospy
What sort of things are used in the management of DMD?
Research into gene therapy such as axon skipping.
Physiotherapy to prolong time able to walk etc
Steriods including corticosteroids
Mobility aids
Technology aids
Adaptors, long straws, chair lifts, eye movement recognition software.
Cell therapies
Up-regulation of alternative proteins
increase in muscle bulk.
How are steroids used in DMD?
Gold Standard of treatment for the last 15yrs
Usually starts around age 4-5yrs
Often prednisolone or deflazacort every day for rest of life
Anabolic steroids mimic the action of tostesterone.
Help delay muscle weekness and maintain the level of muscle mass
Why is the use of steroids in DMD controversial?
Severe side effects.
Obesity
Temper tantrums
Suppressed growth so often short
Weekens vertebrae and bones so often more likely to fracture.
