In the early 1900s, researchers noticed children with the condition were frequently the last-born in large families and came shortly before a woman experienced menopause. At the time, they believed the condition was a sign that the mother had simply exhausted her reproductive potential.
Decades later, a French pediatrician made the association between the condition and an extra chromosome that was present in skin cells of some of his patients. We now understand even more about Down syndrome, including another cause that may run in families and is not associated with a woman’s age at the time she conceives.
But what’s really groundbreaking is we are starting to understand why maternal age matters for the development of Down syndrome.
More women are waiting to have childrenOn average, women in the United States are waiting later and later to have their first child. A recent report from the Centers for Disease Control and Prevention found that in 2014, the mean age of women having their first baby rose from 24.9 years to 26.3 years.
The report also found 9.1 percent of the first births happened in women over age 35, which is typically when we talk about an increased risk of chromosome abnormalities. Twenty percent of first births were in women age 30 to 34. For those women, subsequent additions to their families are accompanied with increasingly higher risks of chromosome abnormalities.
Causes of Down syndromeThere are actually three different causes of Down syndrome.
The most common is trisomy 21, which accounts for about 95 percent of all cases. “Tri” designates three – so instead of having two copies of chromosome 21 in each cell in the body, there are three. This typically happens when there is uneven division of the chromosomal material in the mother’s eggs – more on that later.
Another cause of Down syndrome, accounting for about 4 percent of cases, is translocation. This means that either a full or partial copy of chromosome 21 attaches to another chromosome. The presence of that extra material, even if it’s not a full chromosome, is enough to cause the characteristics of Down syndrome.
And finally, a very small percentage of cases are due to the child having a mixture of normal cells that contain two copies of chromosome 21 as well as some cells that contain three copies of the chromosome.
Chromosomal abnormalitiesWe know that 10 to 30 percent of all fertilized human eggs contain the wrong number of chromosomes. About 5 percent of all clinically recognized pregnancies have some chromosome abnormalities. Many of those early pregnancies end in miscarriage.
But about 0.3 percent of all babies born alive have some sort of chromosome abnormality. The most common is trisomy 21.
Your physician will offer you a test to estimate the risk for Down syndrome in your pregnancy. The test is optional, depending on your thoughts about screening for this disorder. If it’s important for you to know, accept the screening. If having a baby with Down syndrome or knowing prior to birth doesn’t matter to you, then I’d suggest skipping the screen.
A woman is born with all the eggs she will ever have, and they age as she ages. This is different from men, who produce new sperm on a regular basis. By the time a woman reaches 40, as many as 60 percent of her eggs will contain an abnormal number of chromosomes.
In other words, chromosomal abnormalities are more likely to develop in the eggs of older women. But why should that be?
How do chromosomes work?To understand the connection between a woman’s age and potential chromosomal abnormalities in her children, let’s reach back to high school Human Biology.
Everyone has 23 pairs of chromosomes in most cells in the body. The exceptions are eggs and sperm. Chromosomes carry DNA, the genetic information that determines everything about us. Each chromosome is made up of two sister strands of DNA.
As mentioned above, women are born with their eggs already present in their ovaries. At birth, the chromosomes within those eggs are paused in the process of dividing. Division resumes during ovulation and is completed when the egg is fertilized by a sperm cell.
In the initial division, each pair of chromosomes within the egg separates into single chromosomes. During the second round of division, the individual sister strands of each single chromosome separate. The central portion of the chromosome plays an extremely important role in the equitable division of the chromosomes.
The egg must go from having 23 pairs of chromosomes (46 total chromosomes) down to having just 23 single chromosomes. This is so that when the egg and sperm join together, they produce an embryo whose cells each contain 46 chromosomes.
If the division of the chromosomes is uneven, after fertilization the resulting embryo may have one fewer chromosome than normal (monosomy) or an extra copy (trisomy).
Connecting the dots between maternal age and chromosomal abnormalities
Recent studies involving mice helped shed some light on why maternal age plays an important role in the chance a fetus will have trisomy 21.
There are proteins present that help keep chromosomes together at their centers. Lower levels of these proteins – named cohesin and securin – cause the chromosome pairs or sister strands to be more loosely connected and further apart.
Researchers found that older female mice had lower amounts of these proteins in their eggs, suggesting that as the eggs age, the levels of these proteins fall.
You might wonder, as I did, why being less tightly connected or further apart would lead to an increased chance of the chromosomes not separating properly. It turns out this leads to instability in the chromosome pairs and a higher likelihood that chromosome division will happen unevenly. The result could lead to an increased chance of older mice having offspring with an abnormal number of chromosomes. When researchers increased the amount of securin in older eggs, they found that the strands of DNA remained closer together.
These studies were in mice, but may be applicable to human eggs. This knowledge eventually might provide opportunities for therapies that prevent an increased risk of chromosome disorders like Down syndrome in older women.
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