Genetics and Neuro Flashcards
What is DMD?
-Duchenne Muscular Dystrophy
What form of genetic condition is it? Autosomal_____
X-linked Autosomal Recessive
—-seen in 1 in 3000
How does DMD present as?
- delay in motor develop. (can’t keep up with peers)
- CLUMSINESS (1st sign)
- weakness at shoulder and pelvic girdles
How fast does DMD progress?
- onset at 3-4 years
- wheelchair bound by 10-12 years
- DEATH by the time in 20s (involv. of respiratory and cardiac m.)
What is the characteristic posture of DMD pts?
- trunk leaning forward
- shoulder and pelvis in tucked in line with feet
Apart from posture, what is a physical finding of DMD pts?
- pseudohypertrophy of the calf muscles
What genetic mutations bring about DMD ?
- loss-ofxn mutation in the dystrophin gene located on the SHORT arm of the X-chromosome LEADS to dystrophin deficiency
- large scale dle
What is dystrophin?
a V.Large protein found in skeletal and cardiac muscle, brain and peripheral nerves
What genetic changes are seen in 70% of DMD boys?
- large scale deletions
How is DMD diagnosed?
- hx of developm. delay
- muscle weakness signs (toe walkin/ gower’s sign)
- raised serum Creatine Kinase
- EMG (electromyography)
- muscle biopsy
- molecular genetic testing (screen for deletions)
What measures should one with family members if boy is found to have DMD?
- with consent test for mutations in female relatives
- offer prenatal testing in those with known dystrophin mutations
How common is huntington’s disease? And at what age?
1 in 20 000
- 30-50 y.o
What is huntington’s ?
A progressive neurodegenrative disorder
What does huntington’s disease result in?
- dementia
- involuntary movements
- —severe dependency and death over 15-20 years
Define penetrance of a gene?
- the probability of a gene being expressed
- despite having a dominant allele the phenotype may not present
What is the genetic predisposal of person to Huntington’s Disease?
- autosomal dominant trait
- age dependant penetrance (variable(
What are the earyl clinical signs of Huntington’s disease?
- clumsy/ agitated
- apathy
- anxiety
- DISINHIBITION
- delusions/ hallucinations
- depression
- abnormal eye movements
What are the later clinical signs of Huntington’s ?
- dystonia
- trouble with balance/ walking
- slow voluntary movemtns
- wgt loss
- speech defects/ stubborness
- much later: can’t speak/ swallow/ walk/ may choke
What gross pathology is seen in the brain?
- caudate atrophy
What form of predicitve testing can be done?
- pre-natal testing
- pre-gestational testing
What pathological problems occur in Huntington’s?
- LOSS of GABAergic neurones of the BASAL ganglia
- atrophy of the CAUDATE nucleus and putamen > enlargement of frontal horns of the LATERAL ventricles
What genetic CHANGES are seen in Huntington’s?
- CAG repeats
(esp. bad is inherited allele is paternal) - usual copies of 10-30 is amplified to >36
Why is the no. of repeats clinically relevant?
- the greater the number of copies the EARLIER the AGE of onset
What occurs in spinal muscular atrophy pathologically?
- progressive LOSS of anterior horn cells in spinal cord and brain stem nuclei
- resulting in weakness and wasting in muscles used for movement
What are the clinical findings of spinal muscular atrophy?
- HYPOTONIA
- proximal muscle weakness
- TONGUE fasciculation’
What is the genetic form of the spinal muscular atrophy ?
- autosomal recessive
Deficiency in what gene results in spinal muscular atrophy?
SMN1 —responsible for coding SMN protein (resp. for MAINTAINING motor neurones)
Which muscles are likened to be worse with weakness?
- proximal ones
- —-also gets WORSE with age
At what age does alzheimer’s set in?
- in OLD age (over 80yrs in 1 in5 people)
What are the plaques formed in Alzheimer’s made of?
extra cellular protein containing amyloid beta-protein
What is the genetic etiology of Alzheimer’s?
- autosomal DOMINANT (5-10%)
- Down syndrome (onset in 3rd or 4th decade)
Alzheimer’s mutations are seen in which genes?
- APP mutations
- Presenilin 1
- Presenilin 2
What is the relation between alzheimer’s and APOE?
- having APOE4 is said to incr. risk of AD by driving earlier and more abundant amyloid pathology in the brains of APOE*e4 carriers
