Robertsonian translocations: what to do?

Robertsonian translocations are caused by the two acrocentric chromosomes’ loss of the satellites (short arms). The long arms then fuse forming a single chromosome. The loss of the satellites of acrocentric chromosomes does not cause clinical problems, as these satellites contain genomic material which is not essential for life. Therefore, carriers of a Robertsonian translocation are healthy.

However, carriers of a Robertsonian translocation have fertility problems or recurrent pregnancy loss (RPL) and are at risk of conceiving children with an unbalanced karyotype. This is because Robertsonian translocations can lead to severe genetic imbalances in gametes (eggs and spermatozoa), where the chromosomal pool has to split in half to match with the partner’s other half.

For instance, a carrier of a Robertsonian translocation involving chromosome 21 is at risk of having a baby with Down syndrome (trisomy 21).

Since the genetic imbalances caused by a Robertsonian translocation can be considerable, the risk of having an affected child is lower than the prevalence of infertility or recurrent pregnancy loss in these couples. Indeed, gametes or embryos with a chromosomal imbalance caused by a Robertsonian translocation are likely to be negatively selected before fertilization or depleted at early stages during gestation.

However, the risk for couples with a Robertsonian translocation to have an affected child at birth has been estimated:

• Robertsonian translocation rob(13:14): the overall risk of an affected newborn is estimated to be around 1%. This includes the specific risk of conceiving fetuses affected by Patau syndrome (trisomy 13). These fetuses usually cause early pregnancy loss, with only 0.4% of cases giving a viable gestation. The condition may be detected by early prenatal genetic diagnosis.
• Robertsonian translocations involving chromosome 21: when one of the parents is a healthy carrier of a Robertsonian translocation involving chromosome 21, the risk of having a baby affected by Down syndrome is estimated to be 10-15% when the carrier is the mother and 0.5%-2.5% if the carrier is the father. The difference in risk estimates is because spermatozoa are much less permissive than eggs for what concerns genetic imbalances.
• Other Robertsonian translocations involving chromosomes 13, 14, 15 or chromosomes 13, 14, 15, and 22: the risk of an affected newborn is low and is estimated to be around 1%.
• Robertsonian translocations between homologous acrocentric chromosomes (e.g. 13:13, 14:14, or 21:21): in this case, the risk of affected offspring is 100% (the couple can only conceive affected fetuses at each pregnancy and independently from the fetal sex).

As said above, a carrier of a Robertsonian translocation is more likely to experience infertility or recurrent pregnancy loss than being at risk of having an affected child. This happens because imbalanced gametes are so genetically affected, that it’s almost impossible for the embryo to go on in a viable gestation. However, carriers of a Robertsonian translocation may also have healthy children. So, some of the typical questions posed by couples with a Robertsonian translocation are:

• What is our actual risk for (another) miscarriage?
• How likely are we to have a healthy baby?

Having explained the high risk of abortion in carriers of Robertsonian translocation, it’s not easy to precisely quantify the risk of abortion at each pregnancy. However, in a study on 45 gestations, 80% of these resulted in spontaneous miscarriages, while the remaining 20% gave birth to alive or dead children.

As the risk for recurrent pregnancy loss is high for carriers of a Robertsonian translocation, couples often ask what they can do to reduce this risk. A possibility is PGD (Preimplantation Genetic Diagnosis). PGD and transfer of a normal (or balanced) embryo have improved live birth rates and decreased miscarriage rates. However, until recently, there was no genetic technique available in routine diagnostics to distinguish between an embryo with a normal karyotype and an embryo with a balanced translocation (although the clinical outcome would be predictably the same). By utilizing SNP microarrays, it is possible to make such a distinction (although the technology might not be available at all fertility centers).