Numerical and Structural Anomalies

Question 1

What is euploidy defined as?

Answer 1

Exact multiples of the haploid set of chromosomes

Question 2

What is triploidy due to? What is it not compatible with?

Answer 2

1. Failure of meiotic divisions to give rise to a 2N gamete so haploid gamete from other parent fertilizes and gets triploid zygote
2. Dispermy, which will have two sperm fertilize an egg
   Life

Question 3

What is aneuploidy? Give examples of the nomenclature; what is the only viable monosomy? What are most aneuploidies due to?

Answer 3

Gain or loss of chromosomes equaling less than one complete complement: e.g. 47,XX,+13 (trisomy 13); 45,XY,-8 (monosomy 8)
Monosomy 45,X;
Meiotic or mitotic nondisjunction errors

Question 4

What is Trisomy 13 known as?

Answer 4

Patau syndrome

Question 5

In mosaicism, with mitotic nondisjunction, what types of cells would survive and which lineages would die out?

Answer 5

Disomy, trisomy; most monosomies, tetrasomies

Question 6

What is the definition of mosaicism?

Answer 6

Presence of at least 2 different cell lines with at least one clear variation between them

Question 7

What are two examples of mosaicism? How does one get it?

Answer 7

Numerical change (45,X and 46,XX); structural change (one cell line has translocation, other doesn't);
Always acquired!!

Question 8

What are three viable autosomal trisomies?

Answer 8

Down syndrome (trisomy 21); Patau syndrome (trisomy 13); Edwards syndrome (trisomy 18)

Question 9

What are some clinical features of Down syndrome?

Answer 9

1. Most common cause of mental retardation 2. short stauture 3. flat facies 4. protruding tongue 5. short hands, up slanting eyes, low set ears, usually infertile

Question 10

What defects will those with Down syndrome have and what are they at increased risk for?

Answer 10

Heart, lung, brain, endocrine;

Infectious disease, leukemia, Alzheimer

Question 11

What are clinical features of Patau?

Answer 11

Cleft lip and palate; rocker bottom feet; polydactyly, “punched out” scalp; small head, failure to thrive;
less compatible with life than trisomy 21

Question 12

What are clinical features of Edward?

Answer 12

Low birth weight; small mouth/jaw/ VSD/ hypoplasia of muscles, low-set ears, rocker bottom feet, CROSSED FINGERS; patients can’t talk, walk, or care for themselves if they survive past one month

Question 13

Why are sex chromosome aneuploidies more compatible with life than autosomal aneuploidies?

Answer 13

X-inactivation

Question 14

What are four examples of sex chromosome aneuploidies? How do they result (M or P)?

Answer 14

Klinefelter (47,XXY); XYY male, XXX female, Turner syndrome (45,X);
all except XYY (exclusively P) can result from maternal or paternal error

Question 15

What do 47,XXX females have to go through? Are they easy to detect?

Answer 15

Average to tall stature; learning deficit possible; possible fertility problems
usually undetected throughout life

Question 16

What are features of an XYY male?

Answer 16

Tall stature, normal intelligence, normal fertility, clinically indistinguishable from 46,XY

Question 17

What are features of those with Klinefelter syndrome (47,XXY)?

Answer 17

Tall stature, infertility (small balls, hyalinized testicular tubules), female characteristics (breast development, post pubertal hypogonadism); possible learning deficit and behavioral problems

Question 18

What are some key features of Turner syndrome?

Answer 18

Short, webbed neck, edema of hands and feet at birth and later short hands and fingers; shield chest; low posterior hairline, could have children with X/XX mosaicism but otherwise infertile

Question 19

What karyotype will most Turner syndrome patients have? What do some of these patients have?

Answer 19

45,X; some are mosaics, with 45,X/46,XX or 45,X/46,XY (increased risk of gonadoblastoma)

Question 20

If one has the 45,X/46,XY mosaicism, what phenotype would they have? What is the worse one to have and what is indicated?

Answer 20

Male or female;

Female because of increased risk of gonadoblastoma (need surgery)

Question 21

What are some Turner syndrome issues? How can you treat it?

Answer 21

Monitor for heart malfunctions, short stature, probably infertility;
Karyotype to be sure there is no Y chromosome; donor egg; growth hormones

Question 22

What is the basis of the XY female? Where is the mutation?

Answer 22

Androgen insens: mutation of androgen receptor gene on long arm of X chromosome; TDF is present, but androgen receptor protein not present between testosterone and DHT

Question 23

What will this XY female look like? Problem?

Answer 23

Phenotypically normal but with testes; infertility!

Question 24

What is the defect in the XX “male”? What is the defect due to?

Answer 24

CAH with lack of 21-hydroxylase; androgens accumulate and fetus undergoes virulization with normal ovaries and internal genitalia, but ambiguous external genitalia;
can be due to mother OR fetus!!

Question 25

What about the XX male? What type of phenotype is possible? What happens in the reciprocal case?

Answer 25

X-Y recombination near the pseudoautosomal region (Klinefelter phenotype); reciprocal translocation results in Turner female phenotype with apparent 46,XY karyotype

Question 26

What are the most common structural chromosome rearrangements (4)?

Answer 26

Deletion, duplication, Transloation, Inversion

Question 27

What are the subtypes of structural abnormalities?

Answer 27

Balanced: all material is present but rearranged (increase risk of meiosis errors; possible clinical abnormality if the break occurs within a gene) Unbalanced: some of the material is missing or duplicated (includes developmental delay and mental retardation)

Question 28

What does deletion lead to? What are the types of deletion? What is an example of a deletion?

Answer 28

Loss of part of a chromosome leading to partial monosomy; Terminal and interstitial; Wolf-Hischhorn Syndrome (terminal deletion of the short arm of chromosome four)

Question 29

What are clinical features of Wolf-Hirschhorn Syndrome? What do these patients need and are at risk for?

Answer 29

Startled or surprised expression; arched brows, long nose with squared off end; short stature, developmental delay; hypotonia (Greek warrior mask!!!); Special ed, seizures!!

Question 30

For deletions, what are small deletions and large deletions associated with?

Answer 30

Minimal clinical abnormalities; | Developmental delay, mental retardation, abnormal features

Question 31

What is a duplication and what does it result in? What are the two types? How do these tend to occur?

Answer 31

Additional copy of a chromosome segment; results in partial trisomy; interstitial and terminal; usually sporadic, but could be inherited from a parent

Question 32

What is characteristic of reciprocal translocation?

Answer 32

Equal exchange involving two or more chromosomes; so long as breaks don't occur in coding regions, should be clinically benign

Question 33

When does the problem arise for balanced translocation carriers? What results in balanced gametes? What results in unbalanced segregation?

Answer 33

Meiosis; alternate segregation; | adjacent 1, adjacent 2, 3:1 segregation

Question 34

What is the significance of balanced translocation?

Answer 34

Increased risk that another pregnancy has unbalanced chromosome complement; perhaps increased risk of infertility or spontaneous fetal loss

Question 35

How can translocations arise?

Answer 35

Inherited (other family members might have rearrangement); de novo

Question 36

What is characteristic of a Robertsonian translocation? How many acrocentric chromosomes remain?

Answer 36

Centromere to centromere translocation of the long arms involving acrocentric chromosomes; 8

Question 37

Where can Robertsonian translocation occur? What is the worse of the two?

Answer 37

Between two chromosomes (13 and 14) or between homologs (e.g. 21;21 translocation); latter more deleterious since you have gametes that could give rise to Down syndrome child or monosomy 21 (not compatible with life)

Question 38

How many breaks are required in an inversion? When would you see possible abnormalities? What are the two types of inversions?

Answer 38

2; when chromosomes break within genes; pericentric (breaks occur on opposite sides of the centromere) and paracentric (breaks occur on the same side of the centromere)

Question 39

In the case of paracentric inversion, what happens if recombination occurs within the inversion loop? Is recombination actually happening?

Answer 39

Recombined abnormal chromosomes are formed: 1. dicentric chromosome with two centromeres that will eventually break down and result in nonviability 2. acentric will have no centromeres and cannot participate in cell division; Yes it is, but you've lost the products

Question 40

In pericentric inversion, is there an inversion loop? What leads to more viable gametes, a larger or smaller inversion?

Answer 40

Yes; a larger inversion will result in smaller duplication/deletion errors