Recurrent Miscarriage

Question 1

What percentage of recognised pregnancies miscarry?

Answer 1

15-20%

Question 2

What percentages of miscarriages are chromosomal abnormal?

Answer 2

50%

Question 3

What are the most common autosomal trisomies reported in abortions?

Answer 3

16, 21, 22

Question 4

What percentage of patau, Edward and DS miscarry?

Answer 4

95% for ed and pau and 80% for DS

Question 5

Recurrence rate for a couple after pregnancy with autosomal trisomy? What possible reason is there if there is recurrance?

Answer 5

1%. Recurrance due to gonadal mosaicism

Question 6

What percentage of couples with recurrent miscarriages have a balanced translocation?

Answer 6

5%

Question 7

What chromosomes can undergo a robertsonian translocation?

Answer 7

Acrocentric - 13, 14,15,21,22

Question 8

What does Guichaoua et al 1990 say about robertsonian translocations and infertility?

Answer 8

Failure of trivalent pairing in58% of cells
12% of cells showed associations of unpaired 14 and 22 short arms with XY sex vesicles - disrupting meiosis and sperm failure

Question 9

How do you describe an inversion?

Answer 9

Needs two breakpoints eg. 46,XX, inv(1)(p2q3)

Question 10

True or false a pericentric inversion does NOT involve the centromere?

Answer 10

False

Question 11

Possible Results of a pericentric inversion at during meiosis?

Answer 11

1) A normal chromosome
2) An inverted chromosome
3) Recombinant chromosome dup p distal(beyond breakpoint ) and q arm missing
4) recombinant chromosome dup q distal and p arm missing

3&4 make up 50%of cells

Question 12

What are the possible results of the inversion loop in a paracentric inversion?

Answer 12

1) Normal chromosome
2) inverted chromosome
3) dicentric recombinant chromosome (tend to be lost in mitosis)
4) acentric recombinant chromosome (lost v.quick in other mitotic divisions )

Question 13

Which has a higher risk of having an abnormal child - para or peri centric inversions?

Answer 13

Para has less risk of abnormal children as miscarriages occur earlier on but may have an increased risk of infertility

Question 14

What is a balanced insertion?

Answer 14

V.rare with high risk of abnormal child
-3 breakpoints - part of one chromosome has inserted into another.

Eg. 7, der7, 12, der12 (q arm of 12 inserted into p arm of 7)
Result is balanced, normal, dup for insertion of del for insertion

Question 15

Risk to carriers or balanced insertions?

Answer 15

Generally clinically normal but may have de novo translocation with the breakpoints disrupting a gene
Often have reproductive problems

Question 16

What do normal chromosome pairs form at meiosis?

Answer 16

A bivalent - paired along whole chromosome

Question 17

What do reciprocal translocations form at meiosis?

Answer 17

Quadrivalent- four different chromosomes pair a long common sequences

Question 18

How do you draw segregation analysis?

Answer 18

Quadrivalent - line up with centromeres on the horizontal axis and chromosomes bend at the breakpoints

Question 19

What are the segregation results of a quadrivalen?

Answer 19

The four chromosomes will segregate to daughter cells to form gametes
Either 2:2, 3:1, 4:0 (usually inviable)

Question 20

What is alternate segregation and what is the outcome?

Answer 20

2:2 segregation (opposites in the quadrivalent) either the balanced products o the normal chromosomes

Question 21

What is adjacent 1 segregation and what are the outcomes

?

Answer 21

2:2 Non homologous centromeres segregate together (from top or bottom of quad)
Adjacent 1 always results in imbalance

Question 22

Adjacent 2 segregation?

Answer 22

2:2 homologous centromeres segregate together (either the left or right two)
Always imbalanced

Question 23

Interchange tertiary trisomy /monosomy?

Answer 23

3:1 derivative chromosomes segregate to separate gametes

Question 24

Interchange trisomy/monosomy?

Answer 24

3:1, always imbalanced: derivative chromosomes segregate together

Question 25

How to draw quad to find out the most likely segregation to have a viable child?

Answer 25

Draw two lines down the longest arms and this will show the most likely

Question 26

What type of segregation does the quadrivalent shape predispose for ? Who is most at risk?

Answer 26

Tertiary trisomy

Female has a higher risk of unbalanced children- offer testing to sisters of male with translocation