PBL 2 Flashcards
(45 cards)
what is muscular dystrophy?
group of familial disorders that cause degernation of skeletal muscle fibres causing progressive weakness and loss of muscle mass
how are muscular dystorphies distinguishable from neuropathies?
as in muscular dystrophy the neuromuscular junctions are not affected
what are the 3 types of muscular dystrophy?
Duchenne’s
becker
mytonic
what are the 2 dystrophinopathies?
Duchenne’s and Becker muscular dystrophy
what are dystrophinopathies?
muscular dystrophy caused by mutations in the dystrophin gene
what is the genetic basis of duchenne’s muscular dystrophy?
X-linked recessive
what is the chance of a boy and a girl being affected by duchenne’s if their mother is a carrier?
50% for girs to be a carrier
50% for boy to be affected
why is Duchenne’s much more common in men?
because they only have a single X chromosome so the affected one will definitely be expressed unlike in females where only one X chromes gets affected
what is lyonization?
X-inactivation
what happens to a female if their X chromosome that is not affected by duchennes is expressed?
then they will be asymptomatic
what happens in females if more cells have the defective dystrophin gene than do not?
they can be manifesting carriers - show slow progressive weakness beginning in the 2nd or 3rd decade of life
how many times is DMD sporadic and how many times is the mother a carrier?
DMD is sporadic 1/3rd of the time and the mum is a carrier 2/3rds of the time
when will DMD clinically manifest by?
5 years of age
when will someone with DMD typically be whellchair dependant by?
10-12 years
what are symptoms of DMD?
frequent falls Gower's sign not walking by 15 months not speaking as well as children their age trouble running or jumping waddling gait walking on toes poor balance walks with legs wide apart walks with arms and shoulders held back large calf muscles muscle pain and stiffness learnign disabilities walks with chest protruded delayed growth
what are late symptoms in DMD?
respiratory failure due to weak diaphragm
scoliosis
dilated cardiomyopathy
arrhythmias
what is Gower’s sign?
using hands to get up from lying/sitting down due to weak muscles around hips and legs
why does DMD present with large calf muscles?
pseudohypertrophy - muscular enlargement through deposition of fat rather than muscle fibre
what is the life expectancy of a neonate with Duchenne’s?
about 27 years
what is the pathophysiology of duchenne’s?
absence of dystrophin in skeletal muscles due to a mutation means we get cell membrane damage due to the protein not being able to anchor cells cytockeletons to extracellular matrix. this cell membrane damage allows Ca2+ to enter muscle cells= necrosis and allows creatine kinase to leave the muscle cell
eventually, muscles are infiltrated with fat and fibrotic tissue, leaving them weak
whats the role of dystrophin?
Dystrophin-associated protein complex acts as an anchor to connect each muscle cell’s cytoskeleton with the extracellular matrix.
how can we diagnose Duchenne’s?
high creatine kinase levels
mutations seen in dystrophin in DNA tests
muscle biopsy to stain for dystrophin
what is the treatment for duchennes?
glucocorticoids to slow down the degeneration
physiotherapy and conditioning to improve the quality of life
how is becker’s muscular dystrophy different to duchennes?
dystrophin is present but it is misshapen due to a missense mutation
symptoms appear later at 10-20 years old
intellectual disability and contractors are not as common/severe
cardiac fibrosis may be the predominant presentation
