Exam #3: Genetic Disorders III

Question 1

What are the trinucleotide repeat disorders?

Answer 1

Abnormal copies of a tri-nucleotide repeat

Question 2

What is the repeat seen in Fragile X Sydrome? How many repeats are needed for symptoms?

Answer 2

CGG
> 230

**Seen in the UTR just after the promoter

Question 3

What is the repeat seen in Huntington Disease? How many repeats are needed for symptoms?

Answer 3

CAG
>36

*****In the exon

Question 4

What is genetic anticipation?

Answer 4

Worsening of the disease & earlier expression of the disease as it is passed down from generation b/c of amplification of the trinucleotide repeats

Question 5

What is the inheritance pattern for Huntington Disease?

Answer 5

Autosomal Dominant

Question 6

What is the inheritance pattern for Fragile X- Syndrome?

Answer 6

X-linked Dominant

**With a reduced penetrance

Question 7

What is Fragile X Syndrome?

Answer 7

This is the leading cause of INHERITED mental impairment & the leading known cause of autism/autism spectrum disorder

Question 8

Which sex is Fragile X Syndrome worse in?

Answer 8

Males

Question 9

What is the difference between Down’s Syndrome & Fragile X?

Answer 9

Down’s Syndrome is NOT inherited i.e. why Fragile X Syndrome is the most common INHERITED cause of mental impairment

Question 10

How is Fragile X-Syndrome diagnosed?

Answer 10

Southern Blot

Question 11

Describe how Fragile X-Syndrome is associated with the number of repeats?

Answer 11

Increased repeats= increased severity of symptoms*

Question 12

What are the symptoms of Fragile X-Syndrome in males?

Answer 12

Mental impairment w/

1) Big ears
2) Big upper jaw
3) Big testicles (macroorchidism)

Question 13

What are the symptoms of Fragile X-Syndrome in females?

Answer 13

Milder symptoms including mental impairment

- Fewer physical findings

Question 14

What is Huntington’s Disease?

Answer 14

This is a severe neurodegenerative disorder caused by a TRE that is inherited in an autosomal dominant fashion

Question 15

What is the mean age of onset for Huntington’s Disease?

Answer 15

35-44 years

Question 16

Describe the progression of symptoms in Huntington’s Disease.

Answer 16

Early
Intermediate
Late

Question 17

What region of the CNS is affected by Huntington’s Disease?

Answer 17

Caudate nucleus has neuronal dropout/ atrophy leading to gliosis

Question 18

What number of trinucelotide repeats is associated with Juvenile Huntington’s Disease?

Answer 18

> 60

Question 19

What is a Robertsonian Translocation?

Answer 19

Unequal translocation where large arms come together

Question 20

What is Edward’s Syndrome?

Answer 20

Trisomy 18 due to chromosomal nondisjuction during meiosis

Question 21

What is the presentation of Edward’s Syndrome?

Answer 21

Low survival rate due to:

1) Heart abnormalities
- VSD
2) Kidney malformations
- Horseshoe kidney
3) Internal organ disorders
4) Prominent occiput
5) Rocker bottom feet
6) Small jaw

Severe mental retardation

Question 22

What is Patau Syndrome?

Answer 22

Trisomy 13 due to a Robertsonian translocation–most die within the first year of life

Question 23

Describe the presentation of Patau Syndrome.

Answer 23

Generally, there are midline developmental defects including:

1) Microcephaly & mental retardation
2) Microphthalmia
3) Polydactyly
4) Clef lip & palate
5) Cardiac Defects
6) Renal defects
7) Rocker-bottom feet

Question 24

Outline the incidence of the trisomies.

Answer 24

Down’s
Edward
Patau

Question 25

What is Turner’s Syndrome?

Answer 25

45, X
- Female

**The problem is the male sperm that is lacking an X chromosome

Question 26

What is Klinefelter’s Syndrome?

Answer 26

47, XXY

Question 27

What are the prenatal & post-natal features of Turner’s Syndrome?

Answer 27

• Common cause of miscarriage
• Cystic hygroma
• Webbed neck
• Puffy hands
• Puffy feet

Question 28

What are the cardiac anomalies that are seen with Turner’s Syndrome?

Answer 28

• Bicuspid aortic valve

- Coarctation of the aorta

Question 29

What is a cystic hygroma?

Answer 29

Not a neoplasm; rather, a failure of lymphatics to drain properly–>leads to the webbed neck

Question 30

What are the features of Turner’s Syndrome that are typically manifested at puberty?

Answer 30

• Short stature

- Absence of ovaries

Question 31

What is a streaked ovary?

Answer 31

Stroma of the ovary without follicles

Question 32

What are the features of Turner’s Syndrome that are typically manifested at puberty?

Answer 32

• Short stature
• Absence of ovaries

*****Failure of feminisization in puberty is the typical presentation (common cause of primary amenorrhea)

Question 33

What causes the extra-X chromosome in Klinefelters Syndrome?

Answer 33

Mother or father passes on an extra X chromosome

Question 34

Describe the phenotype of Klinefelter’s Syndrome.

Answer 34

• Taller stature

- Feminized physique

Question 35

What is the risk of breast cancer in Klinerfelters Syndrome?

Answer 35

20% increased b/c

• Gynecomastia
• Hyperestrogenism

Question 36

When is Klinefelter’s Syndrome typically diagnosed?

Answer 36

Puberty

Question 37

What is Prader WIll- Angleman Syndrome?

Answer 37

Generally, these are two congenital disorders caused by errors in genetic imprinting

Question 38

What is genetic imprinting?

Answer 38

Turning off a gene with methylation

Question 39

Which Syndrome, Prader-Willi or Angelman is associated with the mother? Father?

Answer 39

Methylated & shut off

Maternal= Angleman
Paternal= Prader Willi

Question 40

What are the symptoms of Prader Willi Syndrome?

Answer 40

• Truncal obesity
• Hypogonadium
• Small hands
• “Dull”
• Outbursts of extreme violence

Question 41

What are the symptoms of Angleman Syndrome?

Answer 41

• Wide stance
• Arm position
• Spasticity
• “Happy puppets”