Robertsonian Translocations 101

(Please note that I'm not a medical or genetics professional. The following is intended only to provide a basic summary and maybe a starting point for those wanting to learn more; it's not a substitute for meeting with your doctor or genetics counselor!)

Because my primary infertility problem is a translocation, I refer to it often on this blog and thought it might make sense to explain what it is. A translocation is a chromosomal rearrangement involving the exchange of material between two different chromosomes. Translocations can be balanced, where the exchange is even, resulting in no important genetic information being gained or lost; or unbalanced, where the exchange is uneven, resulting in missing or extra chromosomes. A person with a balanced translocation is phenotypically normal; thus, balanced translocations usually go undetected until a carrier tries to reproduce. People with balanced translocations are at greater risk than usual of creating unbalanced gametes (eggs/sperm), and unbalanced gametes produce unbalanced embryos.

Translocations are diagnosed through a karyotype, a map of a person's chromosomes via a simple blood test. Most doctors wait until a woman has had several miscarriages before suggesting karyotyping. (My previous OB would not test me after my first m/c.) Even in the IVF world, karotyping is not always standard testing, so many couples go through IVF cycles without knowing if they are predisposed to miscarriage and/or abnormal offspring. However, you can request to have your karyotype done and this may or may not be covered by insurance. (My feeling is that $900 is not a lot if you're shelling out $15,000 for an IVF cycle which may incorrectly assume your chromosomes are normal.)

There are two types of balanced translocations: reciprocal and Robertsonian. About 1 in 1000 people is a carrier of a Robertsonian Translocation. Because my translocation is Robertsonian, I will speak mainly about this type. Also, keep in mind that in order to make this understandable (particularly for me), I'm not addressing the major cell division events -- meiosis and mitosis -- which play a huge role in all of this.

Under normal circumstances, human beings have 46 chromosomes - 22 pairs of 'autosome' chromosomes and 1 pair of sex chromosomes. Each pair is a different size and most are comprised of a long arm and a short arm which are fused together at a joint known as a 'centromere.' Five of our chromosomes -- 13, 14, 15, 21 and 22 -- have very short arms and are known as 'acocentric.' Robertonsian translocations are translocations that occur on any of these five chromosomes.

A Robertsonian translocation occurs when one chromosome breaks apart at its centromere (joint) and the long arm fuses with the long arm of another acocentric chromosome, creating a single larger chromosome. Both short-arms are lost in the process, but because they don't contain relevant genetic information, this is uneventful. As a result, a person with a balanced Robertsonian translocation has only 45 chromosomes, but because they are not missing (and have not gained) any important genetic information, they're normal except from a reproductive perspective. Robertsonian Translocations occur in both men and women and can be spontaneous or inherited. The most common chromosomes impacted are 13 and 14, as in my case, but a person can have any of the five chromosomes affected.

This is a what normal chromosomes 13 and 14 look like:





This is what those same chromosomes look like with my translocation:

(You can see that the long arm of chromsome 14 has left its partner and fused to the long arm of the 13. )

With a Robertsonian Translocation, there are six possible outcomes for the embryo (even more in a reciprocal translocation): normal, normal/carrier, an extra 13 (Trisomy 13), a missing 13 (Monosomy 13), an extra 14 (Trisomy 14), and a missing 14 (Monosmy 14). So from an odds perspective, if nothing else played a role, a Robertsonian carrier has a 2 in 6 (33%) chance of producing a normal embryo. This in on top of the inherent rate of abnormals in young, healthy women without translocations. With the proliferation of PGS (preimplantation genetic screening), their rate of normals is now thought to be around 40%. So very roughly, 33% of 40% normals if you're young with a translocation. And if you're my age...it doesn't look very promising.

But let me say this -- many, many people with Robertonsian translocations have several children -- although they often experience one or more miscarriages. Because I started relatively late at baby-making, it's been significantly more challenging. What doesn't have the translocation always seems to have something else. This is why I'm doing IVF -- so I can test the embryos and transfer only normal ones, hopefully saving me from yet another heartbreaking and time-consuming miscarriage. If I were 10 years younger, I might have decided to try naturally until I found a good egg, but at my age I don't have the luxury of time. Unfortunately, I have yet to know if I'm even capable of producing a normal egg, and I have to accept this as a distinct possiblity. But I suppose even if that's all I find out in the end, it's at least more than I have now.