Genetics

Question 1

what is the genetic pattern in Duchenne Muscular Dystrophy

Answer 1

X-linked recessive

Question 2

do all cases of DMD arise from the boys mother being.a carrier

Answer 2

no, 1/3 cases arise from a spontaneous mutation occurring

Question 3

when do symptoms of DMD begin

Answer 3

aged 3-4, picked up when boys are not hitting milestones

Question 4

list the approximate age when boys with DMD will be wheelchair bound and then when they will die

Answer 4

wheelchair bound - 10/12

death - 20s due to respiratory muscles failing leading to cardiorespiratory arrest

Question 5

DMD occurs when there is a mutation in which gene

Answer 5

dystrophin gene

Question 6

what is the function of the dystrophin gene

Answer 6

aids actin and myosin contraction, without it will result in progressive loss of muscle cells and wastage

Question 7

when looking at cells histologically where does dystrophin appear in the cell normally

Answer 7

around the outside in the cell membrane - with DMD it is no longer present

Question 8

what are the 2 types of dystrophin mutations that can occur

Answer 8

large scale deletions of the dystrophin gene (70% of cases)

smaller, point mutations (30% of cases)

Question 9

how does DMD present

Answer 9

developmental delay especially gross motor but can be global
weakness in the pelvic girdle muscles
Gowers sign +ve
exaggerated lumbar lordosis
contractures of the Achilles tendon making walking difficult

Question 10

what is Gowers sign

Answer 10

when asking child to stand up from sitting on the ground they will use their hands to aid them standing up as pelvic girdle muscles are weakened

Question 11

what tests are used to diagnose DMD

Answer 11

raised serum creatine levels - not diagnostic but shows muscle pathology
molecular genetic screening
electromyography
muscle biopsy

Question 12

what is Huntingtons Disease

Answer 12

a progressive neurodegenerative disease of autosomal dominant inheritance

Question 13

when are symptoms likely to begin in HD

Answer 13

age 30-50 but can vary

Question 14

from symptom onset, how long do patients usually live with HD

Answer 14

15-20 years but progress to severe dependancy before this

Question 15

list the clinical signs of HD

Answer 15

involuntary choreiform movements of head, limbs, trunk and face 
associated with dementia 
rigidity 
bradykinesia 
speech and swallowing impaired

Question 16

what is caudate atrophy

Answer 16

loss of cells from basal ganglia, flattens normal convex curve of the lateral walls of the ventricles

Question 17

describe the molecular genetic defect in HD

Answer 17

CAG repeat expansion
CAG codes for glutamine and expansion results in production of abnormal protein with glutamine residues which is neurotoxic

Question 18

the older a patient with genetic predisoposition the lower their risk of HD true/false

Answer 18

true

Question 19

what is the inheritance pattern in spinal muscular atrophy

Answer 19

autosomal recessive

Question 20

in spinal muscular atrophy what gene is affected

Answer 20

SMN1 gene which codes for a specific exon essential for preventing motor neuron loss

Question 21

describe the clinical presentation of spinal muscular atrophy

Answer 21

hypotonia
muscle weakness
wasting of proximal skeletal muscles
all due to loss of anterior horn cells

Question 22

what is the treatment for spinal muscular atrophy

Answer 22

synthetic oligonucleotide injection which splices exon 7 into identical gene SMN2 - treatment only prevents progression does not reverse condition

Question 23

Alzheimers is the most common cause of what disease

Answer 23

dementia

Question 24

describe the pathophysiology of Alzheimers

Answer 24

loss of cortical neurons, neurofibrillary tangles with senile plaques

Question 25

senile plaques contain what protein

Answer 25

amyloid B protein which is a fragment product of APP - amyloid precursor protein found on chromosome 21

Question 26

what condition is associated with an increased risk of developing Alzheimers at a younger age

Answer 26

Downs Syndrome

Question 27

the rarer autosomal dominant forms of Alzheimers have an earlier or later onset

Answer 27

earlier onset