PBL 2 Flashcards
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
what is myotonic muscular dystrophy?
the most common muscular dystrophy beginning in adulthood
it is characterized by progressive muscle wasting and weakness. People with this disorder often have myotonia and are not able to relax certain muscles after use.
what is myotonia?
prolonged muscle contractions
what is the genetic basis for myotonic muscular dystrophy?
autosomal dominant - only 1 copy of the gene needs to be present and is not sex linked
what is type 1 mytotonic muscular dystrophy?
Steinerts disease
There is a trinucleotide repeat of CTG on DMPK gene on chromosome 19 which codes for myotonic dystrophy protein kinase = inhibition of muscle contraction
what is more severe, type 1 or type 2 myotonic muscular dystrophy?
type 1
what is type 2 myotonic muscular dystrophy?
tetra nucleotide repeat of CCTG on CNBP gene on chromosome 3 which codes for cellular nucleic acid binding protein
when does type 2 myotonic muscular dystrophy present?
in adulthood with mild muscle weakness mostly affecting proximal muscles of thighs and hips
what are some complications of myotonic muscular dystrophy?
cataracts, breathing and swallowing weakness, head, neck and facial muscle weakness, heart difficulties, insulin resistance etc…
what is anticipation?
there is earlier symptom onset and greater severity with each generation
why is myotonic muscular dsytrophy worse with each generation?
with each generation we get more repeats and the higher the number of repeats, the earlier and more severe the symptoms are
outline the pathophysiology of myotonic muscular dstrophy?
repeat expansion causes widespread hydrogen bonding between C and G pairs which makes RNA form condensed clumps so other genes cannot be expressed normally and then egene deficiencies lead to myotonic dystrophy
how do we diagnosi myotonic muscular dystrophy?
genetic testing to check for number of CTG and CCTG repeats
electromyography to assess electrical activity in muscles
what is the treatment for myotonic muscular dystrophy?
there is no treatment but you can treat symptoms e..g surgery to prevent cataracts or having a cardiac pacemaker
where does creatinine come from?
creatine is used in ATP formation during muscular effort and is then converted into creatinine which enters the blood stream and is excreted through the kidneys
what is the Healthy Child Programme?
a universal preventative service providing families wth a programme of screening, immunisation, health + development reviews, supplementd by advice around health, wellbeing and parenting
what should effective implementation of the healthy child programme lead to?
strong parent-child attachment and positive parenting
care that keeps children healthy and safe
preventing some serious communicable diseases
healthy eating and increased activity promotion to reduce obesity
readiness for schooll and improved learning
increasing breastfeeding rates
early detection for developmental delay, abnormalities, ill health and safety concerns
what are the 4 areas of development in a child?
gross motor
fine motor and vision
hearing speech and language
social skills and behaviour
how many children will be able to walk by 12 months? and by 15?
50 % by 12 months and 90% by 15 months
when should you worry about developmental delay in terms of walking?
18 months
what is the difference between speech and language in development?
speech is making sounds and language is about the content and organisation
what are some developmental red flags?
regression of skills not fixing and following objects by 3 months not responding to noise not babbling by 1 years limited use of speech at 3 years no smile at 8 weeks not holding objects at 5 months early hand preference not sitting u at 12 months not walking by 18 months persistent toe walking not pointing at objects at 2 years
