Balanced Non-homologous Robertsonian Translocation in a Single Partner
Recurrent pregnancy loss (RPL) is a complicated and frustrating diagnosis and ~50 of the time – no identifiable cause is determined. 4-5% of cases with recurrent pregnancy loss have an underling genetic etiology which can be identified through investigation with maternal and paternal karyotypes.
A balanced translocation results from a complete breakage of DNA from one chromosome with a subsequent fusion of that DNA to a DIFFERENT chromosome. If no clinically significant DNA is lost, we call this a balanced translocation meaning there is still the same relative amount of DNA, it is just in a different location. While you have the same amount of DNA, being in a different location poses a problem for cell division. When the chromosomes separate, since the DNA is not in its original location, an uneven distribution of DNA can result on the embryo and this can result in a healthy child, a healthy child who also has a balanced translocation, RPL, live birth of children with significant genetic disease such as down syndrome, or children with infertility.
A Robertsonian translocation is a specific type of translocation that takes place on chromosomes with acentric (close to one end of the chromosomes) centromeres. A centromere is a site on the chromosomes that is important for separating chromosomes. In the below image, you can see that one of the 22nd chromosomes has fused with the 13th chromosome. Now, when the chromosomes separate that 22nd chromosome will always move with the attached 13th chromosome while the other 13th and 22nd chromosomes separate independently. This increases the probability of creating genetically abnormal embryos.
Robertsonian translocations carry different risk depending on a variety of circumstances: age, partner with the translocation, chromosomes involved and if the result is balanced or unbalanced. If a Robertsonian translocation involves chromosomes 13:14 the risk of a genetically abnormal live birth is about 0.4%. similarly, though slightly increased, other Robertsonian translocations carry about 1% of having genetically abnormal offspring. However, this risk is notable increased if the 21st chromosome is involved in the translocation. Translocations that involve the 21st chromosome have a 10-15% risk of genetically abnormal offspring if the mother is the carrier of the translocation and a 0.5-2.5% risk if the father is the carrier. This sexually dimorphic presentation is due to maternal non-disjunction (a cell division error in females). If the Robertsonian translocation takes place between two homologous chromosomes (e.g. 14:14) then all future offspring will be impacted.
IVF with PGT-A can be useful to decrease risk of miscarriage in this population. However, it is important to note that only about 30% of the embryos will be normal or balanced. This means, 70% of the embryos will not be viable due to aneuploidy from the translocation. This does not account for further aneuploidy associated with maternal age or other clinical impacts.
