Imagine that you are a future parent. Only a few months after your pregnancy, you choose easy genetic screening. The result is back: the fetus probably lacks a piece of DNA at site 11.2 on the long arm of chromosome 22 – a variant associated with serious medical and developmental problems.
You go online and learn that at least 1 in 4,000 people have this microdeletion “22q11.2”, but the real number may be much higher. Read about 180-plus symptoms of Deletion Syndrome 22q11.2, including heart malformations, hypocalcemia, intellectual disabilities, autism and schizophrenia. Discover confusing treatment guidelines, specialist clinics scattered across the country, and a dynamic patient advocacy movement led by the 22q11.2 International Foundation.
Yet the same pathogenic variant – a genetic change or “mutation” known to cause disease – has been found in people with much milder symptoms and some who appear almost unaffected. No one can give you solid risk factors, because our knowledge of 22q11.2 erasure syndrome (also known as DiGeorge syndrome) is met with “detection bias”: only people with treacherous problems are likely to be tested for it.
Faced with such deep uncertainty, what are you doing? Continuing with traditional diagnostic tests, with its invasiveness, discomfort and low risk of miscarriage? And if the result is confirmed, do you terminate the pregnancy?
This type of dilemma is becoming commonplace because of a revolutionary non-invasive prenatal screening technology known as NIPT or NIPS, which can detect genetic variants as early as nine weeks of pregnancy using a simple maternal blood sample. NIPT platforms examine millions of small fragments of circulating DNA that are no longer enclosed in cells; they are free-floating. Most of these fragments of “cell-free DNA” (cfDNA) come from the mother, but some will also come from the fetus. NIPT platforms read cfDNA from different segments of the genome to detect variants in the fetus. If, for example, there are fewer cfDNA segments from the 22q11.2 region than others, the fetus will be marked as “high risk” for 22q11.2 deletion syndrome.
In short, it is a disease risk screen, not a diagnostic tool, but the NIPT avoids the inconvenience of invasive tests such as amniocentesis and the risk these tests carry. It is too it is increasingly covered by large insurers.
NIPT has already helped millions of families, including mine, rule out several serious genetic diseases in early pregnancy, while allowing many others to make informed reproductive decisions when screens open up.
Like article on the first page published in New York Times Recently, NIPT has become a routine part of prenatal care, although most fetuses that have positive screening for rare conditions do not have this option. Like many other screens, NIPT often puts patients in a painful wait, while further diagnostic tests sort out the real versus false positives. To be clear, only invasive tests such as amniocentesis, which analyze DNA taken directly from fetal cells, can confirm a prenatal genetic diagnosis. Like recent recommendation from the Food and Drug Administration, argue belatedly, NIPT companies and health care providers need to be honest about this.
But this question of false positives only scratches the surface of countless dilemmas unleashed by cutting-edge prenatal screening technologies such as NIPT and preimplantation genetic diagnosis (PGD), a process in which a laboratory-fertilized embryo is tested for genetic abnormalities before being implanted. in the womb.
So, what about families whose positive result from NIPT or PGD is confirmed by later diagnostic tests? They are the ones who then have to make the life-changing decision to either continue or terminate the pregnancy. What does this revolution in prenatal screening mean for them, for groups affected by genetic diseases, and for society?
To address these issues, we need to look at the types of genetic conditions that the NIPT and PGD platforms capture. Down syndrome (trisomy 21) understandably dominates the discussion of prenatal screening, but it is the highly visible tip of a much larger, darker iceberg. For each genetic variant that explains a well-characterized condition, there is many others, the consequences of which are much more difficult to determine. Some produce symptoms that are persistently severe, while others are variable or mild, but due to detection bias, we do not know their true extent of impact on health and development. Some are very rare, others not; accurate estimates of prevalence are known to be elusive. Cumulatively, however, these disorders are quite common.
If NIPT and PGD become as widespread and comprehensive as experts expect, many thousands of expectant parents will learn each year that their fetus has a pathogenic variant. But we will not always be able to tell them what this means for the future of their potential child.
Companies often add genetic variants to their prenatal screens as soon as technology can detect them, not because of careful assessment of severity or treatability. Very early, NIPT was expanded to include 1 in 1,000 people with trisomy X (people with three X chromosomes) or XYY syndrome (additional Y). Most people with trisomy X and XYY are so mildly affected that they are it is never even aimed at genetic research. Whole extra chromosomes were just easy targets for new screening technology.
In the last few years, NIPT has expanded to include a range of lesser-known and under-diagnosed diseases such as 22q11.2 deletion syndrome, 1p36 deletion syndrome, and several others. PGD and invasive tests already include these and many more. With fierce competition and rapid innovationit is clear where this is going: mass prenatal genetic screening for an ever-growing list of genomic variants.
Therefore, NIPT and PGD raise ethical issues that do not exactly fit into futuristic discussions about “designer babies” or entrenched abortion debates.
Identifying genomic variants in the fetus is becoming easier and easier, but it will take years of investment to provide reliable information, counseling and care for families facing genetic diagnoses.
Many more parents will face appalling dilemmas about selective abortion, the decision to terminate a pregnancy after a positive prenatal genetic test. Studies show that people often decide to terminate a pregnancy after discovering even mild genetic conditions such as trisomy X and XYY syndromes. After all, as disability advocates do has long been statedincluding a condition for a prenatal genetic test, suggests that it may be incompatible with ‘a life worth living’ – especially in a society that places heavy burdens on families raising a child with a disability, illness or disability.
NIPT and PGD can transform the landscape for genetic disorders and differences. Many more people will come into the world with a diagnosis. But the very demographics of these genetic conditions may change as a result of screening and selective abortion. They are likely to become less common in general, but will also be distorted towards people who are more religious or have less access to genetic testing and abortion services – namely people who are socio-economically disadvantaged. situation or living in solid republican states. Paradoxically, patient advocacy groups dedicated to these conditions may associate with more members, even when the populations they represent are declining.
With so many genetic variants, NIPT and PGD have profound implications for the way we deal with disabilities and developmental differences as a society. This challenges us to think of a rapidly emerging future in which prenatal genetic screening has complex eugenic effects – not because of forced, racist government programs since the early 20th century, but because thousands of legitimate, highly personal decisions will transform the level of population. distribution of some forms of disability and difference. This can be worrying for those of us who passionately support women’s reproductive rights. Nevertheless, non-invasive prenatal genetics is unexplored territory; we have to fight the deep dilemmas it poses.