What is Trisomy 13?

So far our blog posts have focused on Bryce's life and the aftermath surrounding his death, but we haven't spelled out the details of what Trisomy 13 actually is. In this post we will try to answer some of the questions that you might have.

Trisomy 13 (or Patau syndrome) refers to a group of chromosomal disorders where cells receive an extra functional copy of chromosome 13, resulting in three copies (hence trisomy) of chromosome 13 rather than the usual two copies. The extra chromosome 13 can be whole (referred to as 'full' or 'nondisjunctive' Trisomy 13) or a sizeable chunk of chromosome 13 can be duplicated and glued onto another chromosome (which is called a 'translocation'). Most of the time the events leading to Trisomy 13 were set in motion before the sperm and egg ever met (sometimes decades before), which results in every cell in the developing baby having an extra functional copy of chromosome 13. This is the type of Trisomy 13 that Bryce had. Other times the critical mistake occurs sometime after fertilization, and as such some cells are normal in the developing baby, while others have three copies of chromosome 13. These cases are called 'mosaic'. When you read about Trisomy 13 on the internet and see pictures of kids that are 10 years old with Trisomy 13, they are generally of the 'mosaic' flavor, which can lead to less severe form of the disease ('less severe' is relative - this disorder is hugely debilitating).

So, why does one extra chromosome matter? The extra copy of chromosome 13 thinks it's supposed to be there so it behaves like the other two copies and expresses its genes when it is supposed to. Unfortunately, the extra products of the genes on chromosome 13 have consequences for development. Cleft lip and palate. Congenital diaphragmatic hernia. Kidney dysfunction. Heart defects. Blindness. Extra fingers and toes. Fused fingers and toes. Severe mental retardation (IQ = 30-60). A spectrum of other things that you don't want. Bryce appeared to have only the first three at 20 weeks, but other problems (heart defects) would have almost certainly arisen during the third trimester. Bryce's congenital diaphragmatic hernia was what killed him.

What are some of the genes encoded by chromosome 13? Chromosome 13 contains 114 million bases of DNA (all chromosomes together add up to around three billion bases of DNA) and has around 700 protein-coding genes and an unusually high number of 'noncoding' genes, which often serve to regulate how other protein-coding genes are expressed. Coincidentally, Gus works on a class of noncoding genes called microRNAs, which act to regulate the expression of many other genes that encode proteins. The particular group of microRNAs that he focuses on are encoded on chromosome 13.

Now, back to what went wrong. Bryce's Trisomy 13 was not the result of Dianna and Gus having something 'wrong' with their genes. Bryce didn't inherit a disorder that has been passed down through generations in our families. Dianna, Gus (and consequently, Zane) aren't carriers of Trisomy 13. Rather, the nondisjunctive Trisomy 13 Bryce had was a chromosomal traffic accident that happened either in one of Dianna's eggs ~33 years ago (for those of you doing the math, this is back before Dianna was born, when her eggs formed while she was still in her mother's womb), or in Gus' sperm sometime in December 2008. The odds of this happening to Bryce were around 1:13,700. Bryce was the one.

Eggs and sperm each have half the number of chromosomes (23) that all other types of cells do (2 x 23 = 46). This 'half set' of chromosomes is comprised of one of two possible copies of each chromosome, and eggs and sperm are thus referred to as 'haploid'. Haploid eggs and sperm are made from precursor cells that have duplicate full sets of chromosomes. A series of very specialized cell divisions called 'meiosis' occurred in these precursor eggs and sperm to generate haploid eggs and sperm. Evolution decided long time ago that the benefits of these specialized cell divisions (the mixing of genes from your parents) outweighed the risks, so we're stuck with it.

In this specialized cell division process there is a risk that there will be a chromosomal traffic accident, which occurs when a chromosome accidentally diverts to the wrong haploid daughter cell during egg and sperm formation prior to their separation into individual eggs and sperm. In the case of a nondisjunctive Trisomy 13 chromosomal traffic accident, one egg or sperm receives two chromosome 13s (for symmetry, another will receive no chromosome 13 and fertilization involving this egg or sperm will lead to a condition called 'monosomy', which are typically miscarried). So, when there is an extra chromosome 13 in the mix, after the egg and sperm join during fertilization one of the two brings in the excess baggage leading to Trisomy 13.

Incorrect numbers of chromosomes are more common than we had imagined. Recent research has shown that somewhere between 5-25% of all eggs (but not necessarily fertilized eggs; women have thousands of eggs and not all of them ovulate) contain the 'wrong' number of chromosomes (this number is for all chromosomes combined, not just chromosome 13). 1-2% of all sperm contain the 'wrong' number of chromosomes. It is estimated that half of all miscarriages are due to fertilization involving a egg or sperm that carries the wrong number of chromosomes. In general, the most commonly diagnosed trisomies are 21, 18, 13 and the sex chromosomes. Babies with other trisomies rarely survive past the first trimester, and do not make it to full term.

The difference in incidence between eggs and sperm appears to be due to the particulars of how each is made. Sperm is constantly made after puberty and takes about three weeks from start to finish. In contrast, all of a woman's eggs began the process of meiosis while she was still in her mother's womb, but then hit the pause button. These paused eggs wait until just prior to ovulation to complete the first half of meiosis, which is typically 15-40 years later. Something about the nature of this pause increases the risk of a chromosomal traffic accident. This risk gets greater as a woman gets older, which is where the magic number of 35 years old comes from. Particularly for Trisomy 21, the most common of all trisomies, the risk of having a baby with Trisomy 21 (1:300) when the woman is 35 years of age is greater than or equal to the risk of miscarrying due to amniocentesis, which is the unequivocal diagnostic test for all trisomies. Thus, pregnant women who are over 35 typically have an amniocentesis. What exactly happens in a woman's body between the ages of 30 and 35 to increase this risk of trisomies several fold remains to be determined.

Of the children that have Trisomy 13, 90% die by 3 weeks post birth (this includes neonatal death). By the age of one year, the number of fatalities rise to 99%. There are beautiful and rare cases of children that live with Trisomy 13, if you wish to read their stories click here. If there was even a small chance for Bryce's survival, we would have been honored to care for and cherish him. Sadly, Bryce's condition was too severe.

None of this is meant to scare you into not having children. The odds that you will have a healthy child are still much better than the odds that you won't. The take home message here is this: be in awe of your children, of yourself and of human existence. It's amazing that we are this perfect.

If you have any other questions, please let us know. We've read a lot lately.

Much love,

Los Zeiners

P.S. We will answer questions in the comment section. We are already amazed at what we have discovered and encourage you to read the comments.