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Preimplantation Diagnosis for Marfan Syndrome: How the Upcoming US Supreme Court Decision May Affect It

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Considering the many possible implications of the recently-leaked Supreme Court of the United States (SCOTUS) draft majority opinion regarding a Mississippi law that would ban abortion at 15 weeks gestation, I could have begun musing in any of several directions. Rather than discussing how abortion itself will become illegal in many US states, assuming the leaked opinion —or something very close to it— defines the decision of the Court, I decided to begin from the perspective of reproductive technology. Doing this adds to the abortion issue a dimension that did not exist prior to the 1973 SCOTUS decision, Roe versus Wade, that the upcoming decision on the Mississippi law would overturn. That’s because a half century ago, the only pathway for human embryos that survived the first few days of development after conception was implantation in the lining of the mother’s uterus, the endometrium. Implantation the natural way. Today, in contrast, we have in vitro fertilization (IVF), cryopreservation of embryos, and reproductive laboratories can select from a litter of embryos which ones to implant in the aspiring mother and which ones not to implant. That decision in turn can happen as a result of what’s called preimplantation diagnosis. This means using genetic testing to diagnose the presence of a medical condition when an embryo consists of about eight cells. This is after the genetic material of a sperm cell and an ovum (egg) have merged, creating a single-celled zygote, which then divides into two cells, starting the cell division process of an early embryo.

One example of a condition that aspiring parents often want to have diagnosed prior to implantation, in order to prevent an embryo from developing into a baby, is Marfan syndrome (MFS). This is what geneticists call an autosomal dominant condition, meaning that if one parent is afflicted with it, the chances are 50 percent that any given embryo from that parent will have the condition too. This also means that in the unusual situation of both parents having MFS, each embryo has 75 percent chance of being afflicted with the condition. For aspiring parents with MFS, the calculations are significant, because the condition carries some very severe risks, including that the aorta, the artery receiving blood directly from the heart’s left ventricle, will tear, with potentially fatal results. Informed as to which of their embryos are afflicted with MFS and which are not, many mothers who have the condition themselves (or who created embryos with men who have MFS) choose to have only their unafflicted embryos implanted. It seems like a straight calculation, given the fact that IVF typically produces more embryos than will be implanted in an aspiring mother anyway, or that would survive to the point of a healthy birth. But since Justice Samuel Alito wrote the draft opinion in a way that equates an eight-cell embryo to a newborn infant, this suggests that states that are on track to prohibit abortion will just as easily prohibit preimplantation diagnosis and the selection of healthy embryos for implantation —even in cases as fundamentally clear as MFS, for which a positive genetic test that a person, or an embryo, definitely has the condition itself, rather than just a risk of developing it. With this is mind, let’s delve a little more into MFS.

Showing up as a defect in connective tissue, MFS affects about 1 per every 5,000 people in the United States. Males and females are affected equally and the connective tissue defect is due mostly to the presence of a defective form of a protein called fibrillin-1. The defect is due to a mutation in the FBN1 (also called MFS) gene, although mutations of other genes also are associated with MFS. Connective tissue is affected throughout the body. This can cause problems with joints and eyes (such as retina detachment). Typically, the defect also causes people with MFS to be tall, with long, lanky limbs and fingers. For this reason, historians have suspected that Abraham Lincoln, the pharaoh Akhenaten, and some others have suffered from MFS. Most critically, the connective tissue defects of MFS affect the cardiovascular system, causing weakness in the walls of arteries, including in the ascending aorta, through which all the blood needs to pass. On top of the concern of having a 50 percent chance of each pregnancy producing a baby with MFS, a mother with MFS must consider the danger to herself that pregnancy imposes on her. As we discussed in a previous article about how the circulatory system changes in pregnancy, one of the most dramatic things that happens as pregnancy progresses is that the volume of blood in the mother’s body increases substantially. This volume expansion puts extra stress on the aorta, increasing the likelihood of a thoracic aortic aneurysm (widening/ballooning of the aorta wall) or the size of such an aneurysm of already present. The increased blood volume also increases the likelihood of an aortic dissection, a tear in the wall of the aorta. These conditions can carry fatal consequences.

Because the increasing blood volume of pregnancy exacerbates the problems in the aorta, a high proportion of cases of MFS are not recognized until pregnancy itself begins and advances. Additionally, women with Marfan syndrome may have skeletal problems such as scoliosis (spine curving sideways) and eye problems that pregnancy may exacerbate. Doctors can minimize the risk of aortic dissection and worsening of an aortic aneurysm by giving various medications, mostly to control the blood pressure. Knowing the risks, some women with Marfan syndrome will decide simply to avoid ever becoming pregnant. However, since the risk of fatal outcomes during pregnancy from complications in the aorta is higher in older women than younger women, a diagnosis of MFS can also lead a woman to have children at a younger age than she might otherwise have decided to do.

David Warmflash
Dr. David Warmflash is a science communicator and physician with a research background in astrobiology and space medicine. He has completed research fellowships at NASA Johnson Space Center, the University of Pennsylvania, and Brandeis University. Since 2002, he has been collaborating with The Planetary Society on experiments helping us to understand the effects of deep space radiation on life forms, and since 2011 has worked nearly full time in medical writing and science journalism. His focus area includes the emergence of new biotechnologies and their impact on biomedicine, public health, and society.

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