Cytogenetics

Question 1

What tests are 80% accurate for Down Syndrome?

Answer 1

Positive results for alpha-fetoprotein, inhibin A, plasma protein A, estriol, and human chorionic gonadotropin

Question 2

What tests is 60% accurate for Down Syndrome?

Answer 2

Fetal ultrasound that shows increased nuchal translucency

Question 3

What can karyotype analysis only be conducted on? How are the cells prepared?

Answer 3

Can only be conducted on nucleated, dividing cells

Cells need to be cultured and arrested before analysis can be conducted

Question 4

Cytogenetic studies are _______ and ________

Answer 4

Time consuming and expensive

Use only when indicated

Question 5

What would a karyotype of a fetus with Drown Syndrome show? How does this result?

Answer 5

Free trisomy 21

Results from non-disjunction during meiosis

Question 6

What is a risk factor for autosomal trisomies (21, 18, and 13)?

Answer 6

Maternal age

Question 7

Does the frequency of sex chromosomes abnormalities depend on maternal age?

Answer 7

No it does not

Often have different origin (anaphase lag or Y chromosome instability)

Question 8

What do aneuploidies increase the risk of?

Answer 8

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

Question 9

What does a child present with at birth who has Down Syndrome?

Answer 9

Characteristic facial appearance

Redundant nuchal tissue

Single transverse palmar crease

Question 10

What does Down Syndrome increase the risk of?

Answer 10

Alzheimer Disease

Amyloid precursor protein (APP) gene is on chromosome 21

Question 11

What can familial down syndrome be due to?

Answer 11

3-4% of Down Syndrome cases are due to translocation between chromosome 14 and 21

Question 12

What does the pedigree show in familial down syndrome? What is going on with the chromosomes?

Answer 12

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

Question 13

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?

Answer 13

Mosaicism is suspected

Question 14

How does Mosaicism occur?

Answer 14

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

Question 15

About 1% of Down Syndrome cases are _______

Answer 15

Mosaic

Question 16

What is the origin, recurrence risk, outcome, and frequency of Free Trisomy 21?

Answer 16

Origin - Nondisjunction in meiosis, usually maternal

Low recurrence risk

Outcome is Down Syndrome

> 90% cases

Question 17

What is the origin, recurrence risk, outcome, and frequency of Translocation (Down Syndrome)?

Answer 17

Origin - Recombination event, often with Chr 14 and 21

High recurrence risk if present in parents

Familial Down Syndrome results

2-4% of cases

Question 18

What is the origin, recurrence risk, outcome, and frequency of Mosaicism (Down Syndrome)?

Answer 18

Origin - Nondisjunction in mitosis during development

Low recurrence risk

Unclear outcome, depends on degree of mosaicism

2-4% of cases

Question 19

What will a patient with Edwards syndrome (trisomy 18) present with in an ultrasound?

Answer 19

Gross abnormalities like brain cysts, ventricular septal defect, overlapping fingers, and foot abnormalities

Question 20

What is Edwards Syndrome?

Answer 20

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

Question 21

What is gynecomastia?

Answer 21

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

Question 22

What is Klinefelter Syndrome?

Answer 22

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

Question 23

What will a patient with Turner Syndrome present with?

Answer 23

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

Question 24

What is the prevalence of Trisomy 21, Klinefelter syndrome, and Turner syndrome?

Answer 24

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)

Question 25

What is Fragile X Syndrome?

Answer 25

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

Question 26

What will Southern blotting show in a patient with Fragile X Syndrome?

Answer 26

Expanded CGG repeats

Question 27

Why would a patient not be affected by Fragile X Syndrome even though he has the CGG repeats?

Answer 27

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

Question 28

What causes the Fragile X Syndrome?

Answer 28

Lack of FMR1 expression due to methylation

Females are mosaic for FMR1 expressions