By: Erica Ferraro
The many sneaky conditions that can lurk beneath the surface are mind-boggling, utterly unknown until you start TTC. While in the infertility community, I have come across men and women with chromosomal translocation issues who had no idea until their doctor ordered a Karyotype genetic test for them, and they discovered that this was their issue in making viable embryos all along.
One of these hidden gems is balanced translocation, a genetic condition that you have probably never even heard of until you find yourself in a fertility clinic or chatting away in infertility support groups. This little translocation can be the hidden culprit behind some couples’ struggles to conceive naturally and their uphill battle with infertility treatments like IVF. Chromosomal rearrangements can be inherited or may occur spontaneously (de novo). It is estimated that 1 in every 500 people carry a balanced reciprocal translocation. Most are unaware of their balanced translocation carrier status and live normal, healthy lives. It is essential to be aware of this potential when going through infertility treatments.
But before we delve into how this balanced translocation messes with fertility, let’s have a mini science lesson on this topic.
So, what is chromosomal translocation? It is when chromosomes decide to play musical chairs and rearrange themselves in unusual ways. There are two main types: Reciprocal and Robertsonian translocation.
Reciprocal translocation is a mix-up party between non-homologous (separate pairing) chromosomes. They exchange parts and end up with two detached fragments from different chromosomes. They are saying, ‘Hey, let’s switch places!’
Robertsonian translocation is when two chromosomes get cozy and stick together. It is like they are hugging or blending homogeneously (same pairing).
Sometimes, these translocations can create gene fusions. Two genes that were once apart suddenly become best buddies. Scientists can spot these fusions through fancy techniques like cytogenetics or checking out the karyotype of affected cells.
And let’s not forget about balanced and unbalanced translocations. Balanced means it is a fair trade, like an even exchange of chromosome material with no extras or missing bits. Everything is in order, and functionality is maintained. On the other hand, unbalanced is a bit lopsided. The exchange of chromosome material is unequal, leading to extra or missing genes.
Reciprocal Translocations
The ultimate chromosome exchange party happens in about 1 in 1000 live births. Do not worry; these little swaps usually do not cause any trouble. They are a harmless game of trading genetic material with no gains or losses. But they might raise a flag during prenatal diagnosis, just for kicks. Those carriers of balanced reciprocal translocations, the seemingly normal ones with their chromosomes in harmony, can sometimes create gametes with wonky translocations which can lead to all sorts of mayhem, like infertility, miscarriages, or embryos with abnormalities.
But fear not; genetic counseling and testing are here to save the day. They offer a helping hand to families who might be carrying these translocations. The good news is that most balanced translocation carriers are healthy and symptom-free.
The challenge is that these couples may not only experience infertility and miscarriage at higher rates, but they may also have a more challenging time making genetically normal embryos via IVF. Therefore, PGT-SR testing will likely be required for couples with reciprocal or balanced translocations, as they will likely make more abnormal embryos than is expected for their age, etc. PGT-SR testing is typically not covered by insurance and can start at around $4,000, increasing with the number of embryos the couple decides to test.
Robertsonian Translocation
When chromosomes decide to swap parts, one giant metacentric chromosome is born, while a teeny-tiny one may bid farewell with little consequence. That little guy does not pack many genes, so losing them does not cause much fuss. As a result, humans end up with a karyotype of just 45 chromosomes.
But fear not; this fusion does not affect our appearance or traits directly. The short arms of those acrocentric chromosomes share common genes and are present in varying numbers (called nucleolar organizer genes). So, it is all good in the phenotype hood!
Robertsonian translocations can occur with all sorts of combinations of acrocentric chromosomes. The most famous human duo is chromosomes 13 and 14, present in around 0.97 out of 1000 newborns.
Here is the twist: carriers of Robertsonian translocations do not express these traits themselves, but there’s a slight risk of producing unbalanced gametes that can lead to miscarriages or abnormal offspring. For example, if chromosome 21 gets involved, there’s a higher chance of having a little one with Down syndrome.
So, that’s the scoop on chromosome translocation. If you have had issues conceiving without a precise diagnosis or reason, double-check with your fertility clinic to ensure that they have ruled out chromosomal translocations, which are done through genetic Karyotype testing via blood work. When you arrive at a fertility clinic, this testing is not typically done proactively with the regular genetic testing panel, so do your due diligence and ask about it. If you are using donor eggs or donor sperm, you should consider having your genetic contributing partner screened for Karyotype disorders to rule out the potential that they may make a higher number of genetically abnormal embryos with the purchased eggs or sperm.
sources:
The Frequency and Spectrum of Chromosomal Translocations in a Cohort of Sri Lankans – PMC
Moving Mountains For Motherhood 