Cytogenetics Flashcards
What tests are 80% accurate for Down Syndrome?
Positive results for alpha-fetoprotein, inhibin A, plasma protein A, estriol, and human chorionic gonadotropin
What tests is 60% accurate for Down Syndrome?
Fetal ultrasound that shows increased nuchal translucency
What can karyotype analysis only be conducted on? How are the cells prepared?
Can only be conducted on nucleated, dividing cells
Cells need to be cultured and arrested before analysis can be conducted
Cytogenetic studies are _______ and ________
Time consuming and expensive
Use only when indicated
What would a karyotype of a fetus with Drown Syndrome show? How does this result?
Free trisomy 21
Results from non-disjunction during meiosis
What is a risk factor for autosomal trisomies (21, 18, and 13)?
Maternal age
Does the frequency of sex chromosomes abnormalities depend on maternal age?
No it does not
Often have different origin (anaphase lag or Y chromosome instability)
What do aneuploidies increase the risk of?
Fetal loss
Fetuses with XXX/XXY/XYY and trisomy 21 have >60% chance of coming to term
Fetuses with 45,X and other trisomies are often lost
What does a child present with at birth who has Down Syndrome?
Characteristic facial appearance
Redundant nuchal tissue
Single transverse palmar crease
What does Down Syndrome increase the risk of?
Alzheimer Disease
Amyloid precursor protein (APP) gene is on chromosome 21
What can familial down syndrome be due to?
3-4% of Down Syndrome cases are due to translocation between chromosome 14 and 21
What does the pedigree show in familial down syndrome? What is going on with the chromosomes?
Pedigree shows signs of chromosomal disorder like miscarriages and multiple affected children
Chromosomal alteration can be balanced in the parent and unbalanced in the child
A child’s ultrasound and testing show borderline positive Down Syndrome. Aminocentesis/karyotype analysis (FISH) shows 53 cells are 46, XY and 5 cells are 47, XY, +21. What does this indicate?
Mosaicism is suspected
How does Mosaicism occur?
Early somatic cell division produces aneuploid daughter cells and then the trisomy cells line survives
Patient will have two types of cells
Health outcome is hard to predict because it is not clear which organs will be affected
About 1% of Down Syndrome cases are _______
Mosaic
What is the origin, recurrence risk, outcome, and frequency of Free Trisomy 21?
Origin - Nondisjunction in meiosis, usually maternal
Low recurrence risk
Outcome is Down Syndrome
> 90% cases
What is the origin, recurrence risk, outcome, and frequency of Translocation (Down Syndrome)?
Origin - Recombination event, often with Chr 14 and 21
High recurrence risk if present in parents
Familial Down Syndrome results
2-4% of cases
What is the origin, recurrence risk, outcome, and frequency of Mosaicism (Down Syndrome)?
Origin - Nondisjunction in mitosis during development
Low recurrence risk
Unclear outcome, depends on degree of mosaicism
2-4% of cases
What will a patient with Edwards syndrome (trisomy 18) present with in an ultrasound?
Gross abnormalities like brain cysts, ventricular septal defect, overlapping fingers, and foot abnormalities
What is Edwards Syndrome?
Second most common autosomal trisomy
Full trisomy 18 in 95% of cases
Only 10% of affected children survive the first year - serious physical and mental disabilities, heart defects
What is gynecomastia?
Patient will present with behavioral problems and normal IQ
Micoorchidism - male may shows small testes and developing breasts, high pitched voice
Cytogenetic analysis show a 47, XXY karyotype
What is Klinefelter Syndrome?
47, XXY male
Comparably mild phenotype - low risk of fetal loss and second X chromosomes is inactivated (nuclei show Barr bodies)
Delayed puberty
Frequently infertile due to azoospermia
Often presents with learning disabilities and negative self image
What will a patient with Turner Syndrome present with?
Normal prenatal ultrasound of nuchal region
Physical exam shows low posterior hairline, webbed neck and lymphedema on baby. Older child may show short stature, shield like-chest (involvement of SHOX gene on X chromosome)
Cardiac murmur, Ovarian failure, Horseshoe kidney, coarctation of aorta, risk of aortic dissection
Cytogenetic analysis shows 45,X karyotype
Fetal loss is high
What is the prevalence of Trisomy 21, Klinefelter syndrome, and Turner syndrome?
Trisomy 21: Down Syndrome - common (1/700 births)
47, XXY: Male, Klinefelter syndrome (1/500 males, 1/1000 births)
45, X: Female , Turner Syndrome (1/2000 females, 1/4000 births)
What is Fragile X Syndrome?
Second most common cause for intellectual disability
X-linked dominant inheritance
Caused by a CGG triplet expansion in 5’ UTR of FMR1 gene
Expansion of CGG repeat beyond 200 units predisposes to silencing of FMR1 locus
What will Southern blotting show in a patient with Fragile X Syndrome?
Expanded CGG repeats
Why would a patient not be affected by Fragile X Syndrome even though he has the CGG repeats?
Methylation
Affected patient will have more repeats methylated so they do not express sufficient Fmr1 protein
Normal patient has less repeats methylated and express adequate amounts of Fmr1 protein
What causes the Fragile X Syndrome?
Lack of FMR1 expression due to methylation
Females are mosaic for FMR1 expressions
