Genetics and Neuro

Question 1

What is DMD?

Answer 1

-Duchenne Muscular Dystrophy

Question 2

What form of genetic condition is it? Autosomal_____

Answer 2

X-linked Autosomal Recessive

—-seen in 1 in 3000

Question 3

How does DMD present as?

Answer 3

• delay in motor develop. (can’t keep up with peers)
• CLUMSINESS (1st sign)
• weakness at shoulder and pelvic girdles

Question 4

How fast does DMD progress?

Answer 4

• onset at 3-4 years
• wheelchair bound by 10-12 years
• DEATH by the time in 20s (involv. of respiratory and cardiac m.)

Question 5

What is the characteristic posture of DMD pts?

Answer 5

• trunk leaning forward

- shoulder and pelvis in tucked in line with feet

Question 6

Apart from posture, what is a physical finding of DMD pts?

Answer 6

• pseudohypertrophy of the calf muscles

Question 7

What genetic mutations bring about DMD ?

Answer 7

• loss-ofxn mutation in the dystrophin gene located on the SHORT arm of the X-chromosome LEADS to dystrophin deficiency
• large scale dle

Question 8

What is dystrophin?

Answer 8

a V.Large protein found in skeletal and cardiac muscle, brain and peripheral nerves

Question 9

What genetic changes are seen in 70% of DMD boys?

Answer 9

• large scale deletions

Question 10

How is DMD diagnosed?

Answer 10

• 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)

Question 11

What measures should one with family members if boy is found to have DMD?

Answer 11

• with consent test for mutations in female relatives

- offer prenatal testing in those with known dystrophin mutations

Question 12

How common is huntington’s disease? And at what age?

Answer 12

1 in 20 000

- 30-50 y.o

Question 13

What is huntington’s ?

Answer 13

A progressive neurodegenrative disorder

Question 14

What does huntington’s disease result in?

Answer 14

• dementia
• involuntary movements
• —severe dependency and death over 15-20 years

Question 15

Define penetrance of a gene?

Answer 15

• the probability of a gene being expressed

- despite having a dominant allele the phenotype may not present

Question 16

What is the genetic predisposal of person to Huntington’s Disease?

Answer 16

• autosomal dominant trait

- age dependant penetrance (variable(

Question 17

What are the earyl clinical signs of Huntington’s disease?

Answer 17

• clumsy/ agitated
• apathy
• anxiety
• DISINHIBITION
• delusions/ hallucinations
• depression
• abnormal eye movements

Question 18

What are the later clinical signs of Huntington’s ?

Answer 18

• dystonia
• trouble with balance/ walking
• slow voluntary movemtns
• wgt loss
• speech defects/ stubborness
• much later: can’t speak/ swallow/ walk/ may choke

Question 19

What gross pathology is seen in the brain?

Answer 19

• caudate atrophy

Question 20

What form of predicitve testing can be done?

Answer 20

• pre-natal testing

- pre-gestational testing

Question 21

What pathological problems occur in Huntington’s?

Answer 21

• LOSS of GABAergic neurones of the BASAL ganglia

- atrophy of the CAUDATE nucleus and putamen > enlargement of frontal horns of the LATERAL ventricles

Question 22

What genetic CHANGES are seen in Huntington’s?

Answer 22

• CAG repeats
  (esp. bad is inherited allele is paternal)
• usual copies of 10-30 is amplified to >36

Question 23

Why is the no. of repeats clinically relevant?

Answer 23

• the greater the number of copies the EARLIER the AGE of onset

Question 24

What occurs in spinal muscular atrophy pathologically?

Answer 24

• progressive LOSS of anterior horn cells in spinal cord and brain stem nuclei
• resulting in weakness and wasting in muscles used for movement

Question 25

What are the clinical findings of spinal muscular atrophy?

Answer 25

• HYPOTONIA
• proximal muscle weakness
• TONGUE fasciculation’

Question 26

What is the genetic form of the spinal muscular atrophy ?

Answer 26

• autosomal recessive

Question 27

Deficiency in what gene results in spinal muscular atrophy?

Answer 27

SMN1 —responsible for coding SMN protein (resp. for MAINTAINING motor neurones)

Question 28

Which muscles are likened to be worse with weakness?

Answer 28

• proximal ones

- —-also gets WORSE with age

Question 29

At what age does alzheimer’s set in?

Answer 29

• in OLD age (over 80yrs in 1 in5 people)

Question 30

What are the plaques formed in Alzheimer’s made of?

Answer 30

extra cellular protein containing amyloid beta-protein

Question 31

What is the genetic etiology of Alzheimer’s?

Answer 31

• autosomal DOMINANT (5-10%)

- Down syndrome (onset in 3rd or 4th decade)

Question 32

Alzheimer’s mutations are seen in which genes?

Answer 32

• APP mutations
• Presenilin 1
• Presenilin 2

Question 33

What is the relation between alzheimer’s and APOE?

Answer 33

• having APOE4 is said to incr. risk of AD by driving earlier and more abundant amyloid pathology in the brains of APOE*e4 carriers