Disorders (1)

Question 1

What is the incidence of Down syndrome?

Answer 1

1/700 live births

Question 2

What percentage of Down syndrome does not result from trisomy 21?

Answer 2

5%

Question 3

Where in the cell cycle is it most likely an error occurred that led to Down syndrome?

Answer 3

meiosis II

Question 4

What is the most common translocation which leads to Down syndrome?

Answer 4

Robertsonian 14;21

Question 5

If mom has a Robertsonian translocation, what is the risk for Down syndrome?

Answer 5

10-15%

Question 6

In addition to heart problems and obesity, list 7 things people with Down syndrome are at increased risk for:

Answer 6

• Alzheimer’s disease
• gastrointestinal problems
• hearing loss
• eye problems
• hypothyroidism
• hip dislocation
• leukemia

Question 7

What is the incidence of trisomy 18?

Answer 7

1/7,500 live births

Question 8

What gender is more common in trisomy 18?

Answer 8

female (80%)

Question 9

What percentage of cases of trisomy 18 are due to unbalanced translocations?

Answer 9

1%

Question 10

Which trisomy is most associated with CNS malformations?

Answer 10

trisomy 13

Question 11

What is the incidence of trisomy 13?

Answer 11

1/20,000 live births

Question 12

What percentage of cases of trisomy 13 are due to unbalanced translocations?

Answer 12

20%

Question 13

What is the mode of inheritance for myotonic dystrophy (types 1 & 2)?

Answer 13

autosomal dominant

Question 14

What triplet is repeated to cause DM1 and where is it located?

Answer 14

CTG in the 3’ UTR of the DMPK gene

Question 15

Does anticipation occur in DM1, DM2?

Answer 15

DM1: yes, maternal
DM2: no

Question 16

What may be the single feature of a mild case of myotonic dystrophy?

Answer 16

cataracts

Question 17

Which form of myotonic dystrophy has a normal life expectency?

Answer 17

DM2

Question 18

In which form of myotonic dystrophy does the repeat number correlate with severity of symptoms?

Answer 18

DM1

Question 19

Does anticipation occur in Huntington’s disease?

Answer 19

yes, paternal

Question 20

What triplet repeat causes Huntington’s disease when expanded?

Answer 20

CAG in exon 1 of the HTT gene ; causes polyglutamine probably with a toxic gain of function effect

Question 21

What proportion of mothers of boys affected with DMD are carriers vs. occurance of de novo mutations?

Answer 21

2/3 carriers

1/3 de novo

Question 22

What are the IQ implications of DMD?

Answer 22

a drop of ~10-20 points

Question 23

Are proximal or distal muscles more affected in DMD?

Answer 23

proximal are more affected

Question 24

Other than muscle problems, what other features affect boys with DMD?

Answer 24

• cardiomyopathy
• respiratory problems
• slightly lower IQ (down ~10-20 points)

Question 25

Do female carriers of DMD have an elevated CK?

Answer 25

yes, they can, but it depends on X-inactivation

Question 26

What is the cutoff between early and late onset Alzheimer's

Answer 26

60y

Question 27

Which APOE allele is a risk factor and which is protective?

Answer 27

e4: risk factor e2: protective

Question 28

What is the physiological problem in Wilson disease?

Answer 28

inability to metabolize copper

Question 29

What are the main features of Wilson disease?

Answer 29

- liver failure | - neurologic symptoms

Question 30

What is the mode of inheritance of Wilson disease?

Answer 30

AR

Question 31

What is the lifespan in Timothy syndrome?

Answer 31

~2.5 years

Question 32

What is the inheritance pattern of Parkinson disease?

Answer 32

all types: AD, AR, multifactorial

Question 33

At what age does juvenile-onset Parkinson disease onset?

Answer 33

20-40 y

Question 34

What are three features of congenital DM1?

Answer 34

- reduced fetal movements - DD - MR

Question 35

What is the average age of onset of Huntington's disease? How long is the lifespan after onset?

Answer 35

35 - 44y onset | + 15-18 years

Question 36

For Huntington's disease, what are the repeat cutoffs for the following categories? - intermediate - incomplete penetrance / late onset - affected - juvenile onset

Answer 36

- intermediate: 29 - incomplete penetrance / late onset: 36 - affected: 40 - juvenile onset: 60

Question 37

For DM1, what are the repeat cutoffs for the following categories? - premutation - mild - classic - congenital

Answer 37

- premutation: 35 - mild: 50 - classic: 100 - congenital: 1000

Question 38

For DM2, what range of repeat number is found in affected individuals?

Answer 38

75 - 11,000

Question 39

Which type of heart problem is most common in DMD?

Answer 39

dilated cardiomyopathy