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The Ghettoization of Genetic Disease

Non-invasive prenatal testing has opened up difficult moral questions about how we treat vulnerable groups.

Few medical technologies debuted with the explosive growth of non-invasive prenatal testing (NIPT), which went from nothing to a $1.19 billion global industry in four years, according to a recent market report. With better accuracy than other prenatal screens in identifying the most common trisomies, including Down syndrome, NIPT has been embraced by women as a way to avoid both needlessly alarming false positives and significantly more invasive procedures like amniocentesis and chorionic villus sampling (CVS).

But, like all prior improvements in prenatal tests, it has also turned up the volume on objections to the implications of such tests. These are not synonymous with objections to abortion; it is perfectly possible to support an individual family’s right to make an informed decision not to have a child with a disability and, at the same time, to be concerned about the broad societal impact of many families making the same choice.

Our tests, and our angst about testing, both tend to focus on Down syndrome, not because Down syndrome is the condition that frightens us the most, but because we are well equipped to test for it — a classic case of searching for lost keys under the streetlamp. Headlines describe testing as an existential threat to people with trisomy 21, the makings of “a world without Down syndrome.” But talk about “extinction” may mask a more important point: A reduction in the absolute number of individuals with Down syndrome or any other genetic condition will not affect society or decrease our tolerance for disability as much as a rapidly increasing division between who is and who is not at risk.

Anecdotally, genetic counselors across the country will tell you that decisions about what to do when a fetus has a chromosome abnormality vary widely — they vary by region, by ethnicity, by socio-economic status, and by religious affiliation.

The fact is that populations vary tremendously in their access to and their use of prenatal genetic testing. The proportion of women who choose to end a pregnancy after a fetal diagnosis of Down syndrome is often quoted as 90 percent, but this is an unreliable and discredited figure that is based on a single, small, unrepresentative study done decades ago. A meta-analysis of U.S. data published in Prenatal Diagnosis in 2012 identified the mean termination rate as 67 percent, but more importantly, the authors noted that “Heterogeneity across studies suggests that a summary termination rate may not be applicable to the entire U.S. population.” In other words, it depends.

Anecdotally, genetic counselors across the country will tell you that decisions about what to do when a fetus has a chromosome abnormality vary widely — they vary by region, by ethnicity, by socioeconomic status, and by religious affiliation. These decisions reflect personal choices and local norms, but they may also reflect differences in access to prenatal care, prenatal testing, and abortion. A recent study by Caitlin Cooney, one of my graduate students, found that genetic counselors working in regions where multiple new laws restricting abortion had come into effect were significantly more likely to report changes in practice that negatively affected patient care and that limited access to second trimester abortions from 2011 to 2013.

In January 2017, the Guttmacher Institute announced that U.S. abortion rates had reached their lowest level since the Roe v. Wade decision, a result it attributed more to increased availability of birth control than to restrictive legislation. But fundamental inequities are set to be a bigger part of the total picture, as the 2016 election has been followed by a wave of new proposed abortion restrictions, as well as by a rollback of the federal commitment to universal access to birth control. What’s more, the Guttmacher analysis does not look specifically at the availability of second-trimester abortion, which has been reduced by restrictions on specific procedures as well as by laws that limit abortion by gestational age.

Taken as a whole, these trends suggest that Down syndrome will not disappear, but may increasingly be restricted to certain communities, whether those communities are defined by socioeconomic status, ideology, culture, or region. Many people have speculated that the use of prenatal testing might bring with it a decreased tolerance for disability and difference. But there’s a threat more pressing and insidious than extinction: it is the risk that Down syndrome ceases to be something that could happen to anyone and becomes something that happens only to certain people.

Genetic disease has always been our shared vulnerability. When one part of society can opt out of risk, will they continue to feel the same obligation to provide support and resources to those who remain vulnerable?

The emergence of NIPT brings home the point that Down syndrome is only one example of a genetic condition that can be identified before birth, and that many others — probably thousands — will follow. Already many NIPT companies offer tests for a range of microdeletion syndromes, which are individually more rare but collectively more common than Down syndrome. These new tests have not proved as popular as the “traditional” version of NIPT because their positive predictive value remains low: Most “positive” tests turn out to be nothing at all. Despite this, Sequenom introduced MaterniT GENOME in 2015. It’s an expanded version that examines all chromosomes for any deletion or duplication greater than seven million base pairs (a pretty big chunk of DNA that, depending on its location, is likely to harbor multiple genes). Positive predictive values cannot even be offered for this new test, because there are not enough clinical data to calculate the results; effectively, these are experiments masquerading as clinical care. They are bad tests now, but they will improve.

If current social, legal, political, and technological trends continue, the result may be the ghettoization of genetic disease: It will be confined to discrete areas delineated by geography or culture or socioeconomic status. Whatever the impact on the absolute number of cases, this represents a fundamental re-ordering of our relationship with what it means to say something is genetic. Genetic disease has always been our shared vulnerability. When one part of society can opt out of risk, will they continue to feel the same obligation to provide support and resources to those who remain vulnerable, especially if at least some of them have deliberately chosen to accept the risk?

Choice. For many of us who offer people the opportunity to reduce their risk of genetic disease, “choice” is the word on our banner. If choice means anything, it has to include more than the right to terminate a pregnancy. We know that reproductive rights involve access to birth control, prenatal testing, and fully informed decision-making, as well as abortion. But if we are really in favor of choice, it goes well beyond supporting women to negotiate the prenatal decision tree according to their own values and best interests. It requires a commitment to individuals with genetic disease throughout their lives, and social advocacy to make sure that “rarer” does not mean “less welcome.”

As a genetics professional, the ghettoization of genetic disease frightens me because it has the potential to turn our efforts to improve the lives of individuals and families into a vehicle for social injustice. I don’t believe there is a simple answer, but I do believe that the answer begins with, first, awareness, and second, a genetics community that fights for all vulnerable individuals with as much vigor as it fights for reproductive rights.

  • trueheartdoc

    Very true. Your concerns apply to all vulnerable children, even those without genetic disorders.