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
