Exam #3: Genetic Disorders III Flashcards
What are the trinucleotide repeat disorders?
Abnormal copies of a tri-nucleotide repeat
What is the repeat seen in Fragile X Sydrome? How many repeats are needed for symptoms?
CGG
> 230
**Seen in the UTR just after the promoter
What is the repeat seen in Huntington Disease? How many repeats are needed for symptoms?
CAG
>36
*****In the exon
What is genetic anticipation?
Worsening of the disease & earlier expression of the disease as it is passed down from generation b/c of amplification of the trinucleotide repeats
What is the inheritance pattern for Huntington Disease?
Autosomal Dominant
What is the inheritance pattern for Fragile X- Syndrome?
X-linked Dominant
**With a reduced penetrance
What is Fragile X Syndrome?
This is the leading cause of INHERITED mental impairment & the leading known cause of autism/autism spectrum disorder
Which sex is Fragile X Syndrome worse in?
Males
What is the difference between Down’s Syndrome & Fragile X?
Down’s Syndrome is NOT inherited i.e. why Fragile X Syndrome is the most common INHERITED cause of mental impairment
How is Fragile X-Syndrome diagnosed?
Southern Blot
Describe how Fragile X-Syndrome is associated with the number of repeats?
Increased repeats= increased severity of symptoms*
What are the symptoms of Fragile X-Syndrome in males?
Mental impairment w/
1) Big ears
2) Big upper jaw
3) Big testicles (macroorchidism)
What are the symptoms of Fragile X-Syndrome in females?
Milder symptoms including mental impairment
- Fewer physical findings
What is Huntington’s Disease?
This is a severe neurodegenerative disorder caused by a TRE that is inherited in an autosomal dominant fashion
What is the mean age of onset for Huntington’s Disease?
35-44 years
Describe the progression of symptoms in Huntington’s Disease.
Early
Intermediate
Late
What region of the CNS is affected by Huntington’s Disease?
Caudate nucleus has neuronal dropout/ atrophy leading to gliosis
What number of trinucelotide repeats is associated with Juvenile Huntington’s Disease?
> 60
What is a Robertsonian Translocation?
Unequal translocation where large arms come together
What is Edward’s Syndrome?
Trisomy 18 due to chromosomal nondisjuction during meiosis
What is the presentation of Edward’s Syndrome?
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
What is Patau Syndrome?
Trisomy 13 due to a Robertsonian translocation–most die within the first year of life
Describe the presentation of Patau Syndrome.
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
Outline the incidence of the trisomies.
Down’s
Edward
Patau
What is Turner’s Syndrome?
45, X
- Female
**The problem is the male sperm that is lacking an X chromosome
What is Klinefelter’s Syndrome?
47, XXY
What are the prenatal & post-natal features of Turner’s Syndrome?
- Common cause of miscarriage
- Cystic hygroma
- Webbed neck
- Puffy hands
- Puffy feet
What are the cardiac anomalies that are seen with Turner’s Syndrome?
- Bicuspid aortic valve
- Coarctation of the aorta
What is a cystic hygroma?
Not a neoplasm; rather, a failure of lymphatics to drain properly–>leads to the webbed neck
What are the features of Turner’s Syndrome that are typically manifested at puberty?
- Short stature
- Absence of ovaries
What is a streaked ovary?
Stroma of the ovary without follicles
What are the features of Turner’s Syndrome that are typically manifested at puberty?
- Short stature
- Absence of ovaries
*****Failure of feminisization in puberty is the typical presentation (common cause of primary amenorrhea)
What causes the extra-X chromosome in Klinefelters Syndrome?
Mother or father passes on an extra X chromosome
Describe the phenotype of Klinefelter’s Syndrome.
- Taller stature
- Feminized physique
What is the risk of breast cancer in Klinerfelters Syndrome?
20% increased b/c
- Gynecomastia
- Hyperestrogenism
When is Klinefelter’s Syndrome typically diagnosed?
Puberty
What is Prader WIll- Angleman Syndrome?
Generally, these are two congenital disorders caused by errors in genetic imprinting
What is genetic imprinting?
Turning off a gene with methylation
Which Syndrome, Prader-Willi or Angelman is associated with the mother? Father?
Methylated & shut off
Maternal= Angleman Paternal= Prader Willi
What are the symptoms of Prader Willi Syndrome?
- Truncal obesity
- Hypogonadium
- Small hands
- “Dull”
- Outbursts of extreme violence
What are the symptoms of Angleman Syndrome?
- Wide stance
- Arm position
- Spasticity
- “Happy puppets”
