Rp: Genetics - Cyto (#29)

Front 1

Should invasive prenatal testing for chromosome abnormalities be offered to women in an age-dependent manner?
- who should get it?

Back 1

No.
- individuals w/ hx or fam hx of clinically abnormal offspring, miscarriages, and/or infertility; those w/ + 1st/2nd trimester serum marker screening; individuals and pregnancies that are clinically abnormal.

Front 2

Besides CVS, amniocentesis, and PUBS, what other types of samples can be used for prenatal cytogenetic testing?
- major source of error in these samples?

What is the most common POSTnatal tissue used for cyto testing?
- how many days it it kept in culture prior to harvest for analysis?
- How about skin, pericardium, tendon, etc? How long are those kept in culture?

Regardless of what type of tissue you send, what 2 things must you keep all samples?

Back 2

Products of conception (POC)
- mixtures of all the stuff obtained post-miscarriage/termination
- presence of maternal tissue in the sample.

peripheral blood
- 3 days
- 7 days; pericardium is best when pt is deceased.

ALIVE and STERILE.

Front 3

Are the type and proportions of aneuploidies found in SABs different from those found among liveborns?

Is there still a high degree of lethality even among aneuploidies compatible with survival to birth?

Does genetic quantity or genetic quality affect survival?

Back 3

yes

yes

both

Front 4

Newborns with Tri21 are at risk of what thyroid disorder? Should they keep getting screened anually?
- when should pts with tri21 see an opthalmologist?
- should they get a CV workup post-partum?

Back 4

- hypothyroid, yes.
- @1yo.
- yes, w/ echo to eval for AVSD VSD, etc.

Front 5

What can help explain the increased recurrance risk seen in women w/ a previous Tri21 child?

Back 5

1) gonadal (germline) mosaicism
- would result in recurrence of the SAME trisomy

2) increased predisposition to meiotic error
- mut in meiotic genes, differences in a biological aging of the ovary, etc.
- could result in recurrence of the SAME or a DIFFERENT trisomy.

Front 6

What should you do *because* of the increase recurrence risk seen in women w/ a previous child with Tri21?
- should you karyotype the parents?

Back 6

- offer prenatal dx for all future pregnancies
- no; the abnormal meiotic events that produce numerical abnormalities are sporadic events; Don’t expect a clinically normal parent to have a +21 karyotype.

Front 7

What leads to the 1-2% of pts with Down Syndrome that are mosaics w/ a NORMAL cell line?
- are the generally more mild?
- How should you counsel parents if their first child is a mosaic of the type above?

Back 7

1) normal conception --> postzygotic nondisjunction
2) trisomic conception is rescued by nondisjunction or anaphase lag (more common senario, possibly)
- yes

Given that #2 is thought to be the most common mechanism, counseling should proceed as if the child has the standard nondisjunction form of Down Syndrome, even though this will overestimate risk for some parents.

Front 8

Which cause of down syndrome may carry a substantial recurrence risk?
- in which cases will it actually *be* higher?
- what other stuff can result in these cases?
- what is the recurrence risk for a live born down syndrome child in this case?
- what about if you have robertsonian translocation der(21;21) [this is less common]?

Back 8

Tri21 2ndary to an unbalanced Robertsonian translocation, e.g. der(14;21)(q10q10)
- when the translocation is NOT de novo, but was instead inherited from a carrier parent (40-50%).
- balanced carrier + normal parent --> normal, balanced carrier, tri21, (mono21, mono14, tri14 = not compatible w/ life)
- 3-5% if male carrier, 10-15% if female (33% theoretically b/c the other eggs will die)
- 100% live birth, 50% eggs tri21, 50% mono21.

Front 9

Should we do parental karyotyping in cases of Robertsonian translocations (generally speaking, not conformant to a particular one)

Back 9

Yes, as well as prenatal testing (no shit), and discuss risks of a liveborn child with an unbalanced karyotype +13, +21, etc.

Front 10

Given the form of tri21, give the recurrance risk:
- nondisjunction (47, XY, +21)
- mosaicism (47, XY, +21/46, XY)
- Robertsonian (der14;21)(q10q10)
- Robertsonian (der21;210(q10q10)

Back 10

- maternal age related, but low
- same as above for the nondisjunction form
- 3-5% if male carrier; 10-15% if female
- 100% if carrier parent

Front 11

Prenatally: increased nuchal thickening, cystic hygroma, severe lymphedema, hydrops fetalis.
Newborn: lymphedema, webbed neck, broad chest, prominent ears, cardiac abnormalities, usually nl linear growth until 2-3 yrs.
Childhood: low hairline, cubitus valgus, short 4th metacarpels, short stature.

Top of the genetic dz list?
- what evals will be needed and why?
- Genotype of ~50% of cases? What are the remainder?

Back 11

Turner syndrome.
- CV eval to look for bicuspid aortic valve, aortic dissection, coarctation of aorta
- Renal US to look for horseshoe kidney and unilateral renal agenesis
- consider endocrine/GH tx
- early learning intervention

- 45,X (loss of sex chromosome); structurally abnormal sex chromosome... or mosaicism for a normal or abnormal cell line.

Front 12

In which Turner's pts is there an elevated risk of gonadoblastoma?
- tx recommendation?

Back 12

Those in which the Y bearing cell line is present.
- prophylactic gonad removal.

Front 13

Are most Trisomys biased towards occuring in the female or the male?
- how about structural abnormalities?

Are structural abnormalities observed more or less frequently than numerical abnormalities?
- more or less likely to recur?
- what are some general types?
- do we request parental karyotype when a structural rearrangement is observed?
+ why?

Back 13

female
- male bias (75%)
- less.
- more, typically.
- duplication, deletion, ring, inversion, insertion, translocation
- yes
+ b/c if inherited from clinically normal parent, then we predict no increase risk of abnormal outcome. If new, then risk is minimally 6-7% based on data.

Front 14

Is a balanced new chromosome arrangement still a risk?

Back 14

Yes, it might not be truly balanced, or a critical gene might have been interrupted.

Front 15

How should we counsel for future preganancies in those with a child w/ a structural abnormality?

Back 15

Generic empiric Risk: 10-15% for unbalanced live birth.

Actual Risk: difficult to predict since most reciprocal translocations are unique to a single family.

Front 16

Based on the mode of ascertainment, which translocation carrier will have the highest risk of having a liveborn child with an unbalanced karyotype?

a) An individual ascertained because of a previous liveborn child with an unbalanced form of the rearrangement.

b) An individual ascertained because of a history of multiple miscarriages who has no liveborn individuals with an unbalanced karyotype in his/her family

Back 16

1, because the hx "proves" that an individual with an unbalanced segregate can survive to term and afterwards.

2 has lower risk, because the hx suggests (but does not "prove") that the unbalanced offspring are unlikely to survive to term.

Front 17

How does the size of exchanged segments impact risk assessment for unbalanced *live* birth?

Back 17

small distal segments lead to small imbalances and large risks for unbalanced liveborn offspring.

Conversely, large distal segments lead to large imbalances and a relatively low risk for unbalanced liveborn offspring...but a high risk for miscarriages and/or periods of infertility.

Front 18

Which trisomies and monosomies are less compatible (if at all, with life? which are more tolerated?

13, 14, 17, 18, 18, 21, X, Y

Back 18

Trisomies of 13, 18, 21, X, Y
Monosomies of X, Y
= more compatible

Trisomies and monosomies of 14, 17, 19
= less

Front 19

Are most structural rearrangements common/recurring or unique to an individual family?

Back 19

unique.