Genetics of CNS disease Flashcards
What is the inheritance of duchenne’s muscular dystrophy?
x-linked recessive
What is the inheritance of Huntingtons disease?
autosomal dominant
At what age does weakness tend to begin with DMD?
3-4years
Where does weakness in DMD usually begin?
pelvic and pectoral gigrdles
What is the characteristic posture of a boy with DMD?
accentuated lumbar lordosis
What is typically seen in the legs of patients with DMD?
calf hypertrophy
What causes DMD?
deficiency of dystrophin
What is the function of dystrophin?
connects contractile elements eg actin in muscle cell to proteins in the cell membrane
What is the difference between DMD and BMD?
duchennes dont have dystrophin at all whereas BMD have a shortened version of the protein
What is the most common genetic mutation in DMD?
large scale deletion of dystrophin gene in 70%
Why is toe walking seen in patients with DMD?
shortening of their achilles tendon
What are the investigations done fro DMD?
CK; EMG; muscle biopsy; genetic testiing
When is the typical onset of Huntington’s?
between 30 and 50
What are the early signs of Huntington’s?
clumsiness; agitation; irritabililty; apathy; anxiety; disinhibtion; delusions; abnormal eye movements; depression
What are the later signs of Huntington’s?
dystonia; involuntary movements; slow voluntary movements; weight loss; speech difficulties; stubbornness
What happens to the basal ganglia in Huntington’s?
caudate nucleus atrophy (and cerebral cortex)
What is the genetic defect in HD?
increased CAG repeats
What does CAG code for and why does excess repeats cause problems?
glutamine- too much is neurotoxic
What happens to the Huntington gene as it is passed down?
increased exapnsions so decreased age of onset
What is the pathology seen in Alzheimers?
loss of cortical neurones; protein deposits intracellular- neurofibrillary tangles and extracellular- senile plaques
What are senile plaques?
extracellular protein deposits containing amyloid beta protein
What is amyloid beta protein?
a fragment of the product of the amyloid precursor protein from chromosome 21
What genetic condition is associated with early onset Alzheimers?
Down syndrome
What mutations can cause autosomal dominant early onset Alzheimers?
APP mutations of chromosome 21; Presenilin 1- chromsoms 14 and Presenilin 2 on chromosome 1
Which allele of apolipoprotein E predisposes to Alzheimers?
e4
What is the concordance of MS in monozygotic twins vs dizygotic twins?
25% vs 3%
