My friend passed this question on to me. Can anyone see this as a valid question for step 1? A 34 year old woman (P:1, G:1) has a 46XY down syndrome child. Genetic analysis revealed she has a t(14q21q) translocation. Assuming her partner is genetically normal, what are the odds that her next child will be phenotypically normal? A) 1/6 B) 1/4 C) 1/3 D) 1/2 E) 2/3 I'm thinking (D) 2/3 with the assumption that monosomy 21 and monosomy 14 will terminate as abortions.

Dunno how great this website is, but they say the recurrence risk for DS with a balanced Robertsonian translocation is ~12% if the mom's the carrier. 88% isn't even close to any of the possible answer choices though...

Ah... i came across this website: it is 1/2 chance for a normal child with a t(13q21q) source: http://atlasgeneticsoncology.org/Educ/PolyMecaEng.html In terms of the t(14q21q), from the question above, the nih website gives this explanation: source: http://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=hmg.figgrp.219 I guess it all comes down to what the viability of the trisomy/monosomy is. Does anyone know if monosomy 14, monosomy 21 or trisomy 14 are viable?

No monosomies are viable. And the only viable trisomies are 21, 18, 13, and i think 8...i saw it in a qbank.

The mosaic form of trisomy 8 and 16 are viable. Apparently, there is also a viable trisomy 22 that I wasn't aware of. Source: wikipedia.

Correct me if I am wrong, but I don't know if the 2x2 table works for this because of independant assortment of chromosomes. For example, if you get the robertsonian 14, you only have 50% chance of getting the maternal 21. I also don't see how the answer can be 1/2 if you have 3 ways of getting a viable child: 1) Normal 2) Robertsonian 14 (balanced carrier) 3) Robertsonian Downs therefore, with 3 viable options and 3 non viable options (as per the NIH picture above) I think the answer is: there will be a 2/3 chance that the future child will be phenotypically normal.

If the parent has a balanced robertsonian translocation -> the theoretical recurrence risk is 1 in 3. Odds her child would be normal is 2/3. and yes, I could see this as a valid question for step 1. why not?

Same Q in BRS path (genetics chapter, p 62, number 2). The answer is 1/3 that child will have disease (answer from BRS: theoretically a person who carriers a robertsonian translocation with chromosome 21 and a second acrocentric chromosome has a 1/3 chance of having a child with trisomy 21...)