Tag Archives: Genetic counseling

Is A Lab A Health Care Professional? An Update On “Everyone’s Worst Nightmare”

Two years ago I authored a blogpost, Everyone’s Worst Nightmare , about a family’s experience with genetic variant interpretation, communication (or lack of) by healthcare providers with families, and an outcome that couldn’t be more tragic – the death of a child. Here I am providing an update on the legal status of the lawsuit brought on behalf of the child by his mother. In my original posting, I did not identify the child’s syndrome or the specific court case. However, since then, the story has been picked up by a variety of media outlets (Turna Ray at GenomeWeb has done the best reporting on the details) and it now being a matter of public record, I have included some particulars here .

Briefly, the story began about 12 years ago when the child was experiencing multiple, intractable seizures and had a clinical picture consistent with Dravet syndrome. Unbeknownst to the parents, genetic testing was ordered and the child was found to carry a mutation in SCN1A, the gene linked to Dravet syndrome. The mutation was interpreted as a variant of uncertain significance, though at the time there was reason to believe that it could be pathogenic. Based on the genetic test result, it was felt that the child did not have Dravet syndrome and was kept on a sodium channel blocker, which unfortunately is contra-indicated for patients with this syndrome. Not long afterwards the child died of seizures at the age of two.

The patient did not find out that genetic testing had been performed until about 7 years after the test was ordered. Shortly after the mother learned of the test result and inquired into its meaning, the lab reclassified the variant as pathogenic.

In February 2016 the mother initiated a lawsuit on behalf of her deceased child in the fifth judicial circuit court in Richland County, South Carolina. The defendant’s lawyers requested that the case be dismissed on the grounds of restrictions imposed by the state’s statute of repose, i.e., a law that states legal action must be initiated within a certain period from the time the alleged offense occurred (it is similar to but slightly different from a statute of limitations). The defendants presented the argument that a genetic testing laboratory is a licensed health care provider and South Carolina has a 3 year statute of repose for lawsuits brought against licensed health care providers. Since the events took place a decade ago, the defendants asserted that the case should be dismissed. The plaintiff countered that, under South Carolina state law, a genetic testing lab that is separate from a hospital or a clinic cannot be considered a licensed health care provider and therefore the statute of repose did not apply. The plaintiff contended that this is a case of ordinary negligence, not medical malpractice, since the lab should not be considered a licensed health care provider and therefore the suit should be allowed to proceed.

The case was then sent to the US District Court in 2017 to rule on whether dismissal was warranted based on the defendant’s argument that the lab is a licensed health care provider and therefore the statue of repose applies. The federal judge then referred the case to the South Carolina Supreme Court to, as the legal lingo goes, certify the question of whether a lab can be considered a licensed health care provider under the specific provisions of South Carolina Code of Laws Section 38-79-410. Although we may have our individual opinions on this question, it is strictly a matter of law that varies by state. South Carolina law defines a licensed health care provider as “physicians and surgeons; directors, officers, and trustees of hospitals; nurses; oral surgeons; dentists; pharmacists; chiropractors; optometrists; podiatrists; hospitals; nursing homes; or any similar category of licensed health care providers.” (italics added)

The South Carolina Supreme Court heard the case on February 14th, 2018. For those of you who have never witnessed a state Supreme Court hearing, I recommend that you watch the ~40 minute video of the session. The court’s decision, which will be about whether the suit can proceed rather than determining liability, will depend on how it interprets whether a laboratory is a “similar category” to the health professionals listed in the state code. I thought that the five justices were insightful and asked thoughtful questions. As a side note, at about the 29-30 minute mark of the hearing, Justice Few gives a shout out to our genetics colleagues at the Greenwood Genetics Center.

The court does not have a set date on when they will issue an opinion; as the Supremes, they call that shot (the South Carolina Supreme Court’s motto is Nil ultra, which roughly translates as “Nothing is above us”). Typically, though, the time frame on a ruling is in weeks or months. If the court decides that the lab is not a healthcare provider, then the plaintiff’s suit will be allowed to continue, though I got the sense that the court felt that even if the ruling were in favor of the defendants that the plaintiff may still have alternate legal pathways to pursue a case. I will keep the good readers of The DNA Exchange posted on important developments in this case, which I suspect will continue to drag on for some time after the Supreme Court’s ruling.

With the rapid expansion of genetic testing in the clinical and consumer spaces, and the growing involvement of non-genetics professionals in ordering genetic testing, bad clinical outcome scenarios are likely to become more common. Critical questions about variant interpretation and legal liability aside, from a genetic counseling standpoint, this case highlights the importance of clear and ongoing communication with patients and their families about the limits and clinical interpretation of genetic testing. This can be extraordinarily difficult when a family is trying to cope with caring for a child with a life-threatening disease, but genetic counselors are trained to work precisely in those situations. Genetic testing may be simple to order and widely available but it benefits no one without good clinical care and counseling.

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The Rhythms of Silence

“It was a silence filled with many things going on in it.”

– Dorothy Parker

Shut my mouth.  That is one of the hardest things for me to do during a genetic counseling session, though paradoxically it is among the simplest. Despite decades of experience as a genetic counselor, I still have a tendency to dominate my interactions with patients. Maybe all of us are guilty of this to varying degrees. To some extent, it is a natural by-product of a clinical service with a significant educational component. Dialogue easily morphs into monologue.

But genetic counseling does not end at education. Instead the counseling component simultaneously flows from and shapes the educational aspects. I sometimes need a virtual dopeslap upside my head from Jon Weil’s or Seymour Kessler’s spiritual avatar to get things back on track.

How We Talk, a book about conversational analysis by the linguist N.J. Enfield, has helped heighten my awareness of my tendency to dominate counseling sessions. And it is a lot less psychologically painful than Jon’s or Seymour’s dopeslaps.

A typical conversation flows with a rhythm guided by timing cues. Speaker A says something and then Speaker B seamlessly follows with a response to what Speaker A just said, and so the conversational turn-taking flows through to the conclusion of the conversation. In normal everyday conversation the average length of the transition between when Speaker A stops speaking and Speaker B responds is ~200 milliseconds. Literallly in the blink of an eye Speaker B recognizes that it is the appropriate time to speak and has a response ready. The brevity of the silence interval is mute testimony to the stunning complexity of the human brain. Conversation is like a John Cage musical composition based on a pattern of silences. Silence is to conversation as zero is to numbers.

Of course, there are within- and between- individual variations in any conversation. There are also differences between languages, but the differences are slight. For example, in the Mayan language Tzeltal, the average transition time is 67 milliseconds, in Italian it is 310 milliseconds, in Lao it is 420 milliseconds, and in Danish it is 470 milliseconds. English is just above average at 236 milliseconds. No doubt a Dane would drive a Tzeltal speaker crazy with the extended transition time, but the difference between the languages is under half a second, within the range of an eye blink.

The dialogue from the screwball comedies of the 1930s and 1940s move along at dizzying speed because we perceive the transition times as almost non-existent. The great screenwriters intuitively understood this and Cary Grant, Katharine Hepburn, et al., effortlessly deliver witty repartee that leaves your brain gasping for breath.

When the transition time exceeds a half second, and especially as it approaches one second, Speaker A perceives the response as taking too long and tends to jump back into the conversation, “out of turn.” This One Second Rule is called a standard maximum silence. It is often more than a matter of Speaker B needing more time to formulate a response to a complex statement or question. The longer than expected delay can communicate that Speaker B thinks the response is “non-preferred,” that is, something that Speaker B feels may not be the reply that Speaker A wants to hear. And when Speaker A jumps in out of turn, Speaker A will re-phrase in a way that makes it easier for Speaker B to give a non-preferred response. Subtle non-verbal emotional interplay takes place in the space of a silent second. The silence of the iambs. The following fictional counseling scenario demonstrates this:

Scenario A

Counselor: So, do you think you want to undergo this genetic test?

(1 second pause)

Counselor: You don’t have to make up your mind right now.

(800 millisecond pause)

Client: Well, the test could be helpful. I am not sure about my insurance coverage, though.

Here, the 1 second pause suggests that the patient may not want the test, and the “long” pause pushes the counselor to jump in and say something that makes it easier for the patient to decline testing. The patient replies in a way that that the patient feels the counselor prefers to hear – the test is important – but bringing up insurance coverage gives the patient a “legitimate” reason to decline testing. Even though the counselor may feel that she or he was non-directive, the patient may have picked up on a message that perhaps the counselor thinks the patient should undergo testing, even if the counselor is not saying it in so many words.

Generally, Yes/No responses that occur within the first half second of a transition are perceived as more definitive whereas responses that are closer to one second or longer are usually interpreted as ambiguous. The following fictional exchanges between a counselor and a client illustrate this:

Scenario B

Counselor: So, do you think you want to undergo this genetic test?

(200 millisecond pause)

Client: Yes.

 

Scenario C

Counselor: So, do you think you want to undergo this genetic test?

(1 second pause)

Client: Um (3oo millisecond pause) it might be a good idea.

In Scenario B, the short transition time of the client’s response suggests a strong desire to have testing. However, in Scenario C, it takes the client 1.3 seconds to arrive at a form of Yes, the hesitancy in the response possibly reflecting a hesitancy to undergo testing. The interjection “Um” before saying “Yes” reinforces the perception of ambiguity. This 1+ second difference in transition time is a clue to skilled counselors to more deeply investigate the patients’ desires and reasoning, even though the counselors and the clients may not be consciously aware that clients are communicating clues to their ambiguity.

Of course, in the context of a counseling session, a delayed response could be due to the cognitive processing required to comprehend technical medical information or it could be due to psychological processing of an emotionally laden discussion. Which, to some extent, is the point here. A genetic counseling session is not usually an ordinary conversation (though a skilled counselor can make it appear that way), so the turn-taking of the speakers can be expected to have a different rhythm and follow different timing cues. But because we are so subconsciously attuned to the rhythm of normal conversation, the tendency for genetic counselors to sometimes dominate a session may stem in part from relying on the wrong timing cues and to speak out of turn before patients are ready to articulate their thoughts.

An interesting research project would be to record counseling sessions with the purpose of timing transitions between counselor and client. This could then be correlated with outcomes such as patient satisfaction and uptake of recommendations to see if they were influenced by conversational transitions. Transition times could also be used to guide the development of better counseling skills by helping the counselor to understand ways that transition times were used appropriately or inappropriately during the course of a counseling session.

To be sure, transition times are not the only non-verbal influence on the rhythm of a conversation. Posture, gestures, facial expressions, and eye gaze can influence the flow of conversations and serve to articulate the psyche. Reading the body of clients is as important a skill as being attuned to their verbal language. People are generally less aware of their body language and thus it can more “honestly” and directly reveal underlying psychological and emotional processes than verbal language.

It is extraordinarily difficult to be keyed into what Enfield calls “the inner workings of conversation,” especially in the moment of the conversation. It involves unlearning, or more precisely becoming aware of and being able to manipulate, a language protocol that has been subconsciously engrained into us since we burst out of our amniotic sacs. Becoming a good counselor is not simple nor is the path always straight. The graph of professional growth follows a jagged and at times recursive line. There is no breakthrough moment when you permanently become the genetic counseling equivalent of a Jedi Master, able to manipulate the Counseling Force to your will and you are infused with Yoda-like wisdom. Easy it is not.

 

 

 


Thanks yet again to Emily Singh for help with graphics.

 

 

 

 


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Is Down Syndrome Disappearing? Well, Not Exactly But….

Iceland has given the world the Eddas, Sigur Rós, Björk, and some magnificent geology.  A more ambiguous achievement, though, is suggested by a recent CBS News story that claimed that Down syndrome is disappearing from Iceland as a result of prenatal testing. The claim has been bouncing around the Internet for a few years. The earliest reference I could find was a November, 2015 letter sent to the Office of The United Nations High Commissioner for Human Rights authored by Downpride, an international advocacy group for people with Down syndrome. The letter is an “[a]ppeal to the United Nations to stop discriminatory use of prenatal genetic screening aimed at eradication of people with Down syndrome and other groups.” It was, in my view, an understandable and justifiable reaction to largely non-critical widespread adoption of Noninvasive Prenatal Testing (NIPT) from a community that has good reason to be concerned. Needless to say, it generated a lot of heated reaction. Just Google “Iceland Down syndrome” and you will see what I mean.

Delving into the story was like getting lost in a hall of mirrors; many sites simply referenced each other. But the claim that Down syndrome is disappearing from Iceland and that 100% of pregnancies with Down syndrome in Iceland are terminated turns out to be not quite so straight-forward. While Iceland represents a microcosm of the larger concerns of people with disabilities, their families, and their supporters, it is not necessarily an accurate reflection of the macrocosm of the larger population dynamics of Down syndrome in other countries, particularly the United States.

The ultimate source of the data, according to the Downpride letter, was testimony presented to The Althing, the Icelandic parliament that is the world’s longest existing legislative body. I tried unsuccessfully to find that testimony. I then searched PubMed but found only limited help. So I decided to do my own back-of-the-napkin calculations. I obtained the birth distribution by maternal age in Iceland for 2016, and grouped the ages by quinquennia. The expected frequency of Down syndrome was based on data from 1976, prior to the advent of widespread prenatal diagnosis.

Age Group # of Births Exp. Frequency of Down S. Exp. # of births with Down S.
15-19 72 1/1667 0
20-24 592 1/1587 0.37
25-29 1305 1/1087 1.2
30-34 1218 1/763 1.6
35-39 672 1/248 2.7
40-44 165 1/79 2
45+ 10 1/24 0.4
Total 4034  1/488 8.27

 

Thus, in Iceland in 2016, there were 4034 births. In the absence of prenatal diagnosis and selective termination, 8 or 9 babies with Down syndrome would be born, for a frequency of ~1/450-500 births. I then made the following assumptions, acknowledging that each has some potential error:

  • Based on a 2016 publication, about 80% of pregnant Icelandic women will choose to undergo prenatal screening
  • According to Dr. Hulda Hjartardóttir, chief of obstetrics at Iceland’s National University Hospital, among Icelandic woman who have a positive screen, about 25% decline diagnostic testing and continue the pregnancy. Thus, roughly 1/3 of Icelandic pregnant women either do not undergo screening to begin with or decide to continue the pregnancy and not proceed to diagnostic testing if a screening test is positive. The impact of these percentages on Down syndrome frequency depends on the age distribution of those who declined screening or diagnostic testing, but for argument’s sake, I assumed an equal distribution across maternal ages.
  • 100% of women whose pregnancies are diagnosed with Down syndrome will choose to terminate. I could not verify this claim, but I decided to go with the most extreme scenario. This has not been the experience in many countries, where termination rates have been high but not typically 100%.
  • The CBS News story mentions the Combined Screen, so I assumed this was the standard screening test in Iceland when the claims were made in The Althing. I therefore set the detection rate for Down syndrome to 90%, that is, of all women undergoing screening, about 10% of pregnancies with Down syndrome will be screen normal and would not proceed to termination (some studies suggest that the Combined Screen may have a sensitivity somewhat less than 90% but because about 21% of pregnancies in Iceland occur in women 35 and older, a higher sensitivity – and false positive – rate is expected).

Based on these assumptions and the above table, of the potential 8-9 babies born with Down syndrome, about 2-3 would actually be born because their mothers did not undergo either prenatal screening or diagnostic testing, and another baby with Down syndrome would be born because the Combined Screen would be expected to miss about one case. In other words, the total number of newborns with Down syndrome in Iceland would be expected to drop from 8-9 every year to about 3, maybe 4, per year. These numbers could increase or decrease with many factors, such as changes in fertility rates, maternal age distribution, the sensitivity of screening tests, social trends that influence the choice of abortion, and random fluctuations that occur with any demographic trend especially with the small number of births in Iceland (about that many babies were born last year in the hospital where I work in Seattle). If readers know of empirical data from Iceland to support or refute my estimates, please share it.

Of course, for advocates, every loss of a pregnancy with Down syndrome is serious, no matter how small the number. But these estimates put the concerns in some perspective. Among other things, it is fair to say that most, but not 100%, of pregnancies with Down syndrome are terminated in Iceland, and the birth prevalence of Down syndrome in Iceland is falling considerably but not likely, in my view, to disappear entirely.

I think a more realistic picture of the impact of prenatal screening on Down syndrome, in the US at least, is provided by Brian Skotko and his colleagues Frank Buckley, Jennifer Dever, and Gert de Graaf in a recent publication in the American Journal of Medical Genetics. Over the last few years, they have consistently provided some of the most reliable estimates of the demographics of Down syndrome and the effects of prenatal screening.

According to the de Graaf et al. paper, a detailed look at changes over time in the demographics of Down syndrome in 9 states, the number of people living with Down syndrome has steadily increased since 1950. The two major factors driving that growth have been longer survival due to better medical care along with the unrelenting trend of the last 35-40 years of delayed childbearing. This growth, however, has been partially offset by a loss of births with Down syndrome due to prenatal screening. The loss varies with geographic region, but overall, the prevalence of Down syndrome is roughly 70% of what it would be if prenatal screening were not available. Interestingly, the most growth in the Down syndrome population occurred among Hispanics and Native Americans. So, unlike the near elimination of Tay-Sachs disease in many Ashkenazi Jewish communities, the prevalence of Down syndrome is dropping, but not close to disappearing, at least in the US.

Other factors may affect the Down syndrome birth frequency, such as changes in maternal age distribution, availability of abortion, and access to health insurance. For example, in the highly unlikely event that every woman 35 and older refrained from pregnancy, the birth frequency of Down syndrome in the US and many Western European countries would be reduced by more than 50%. On the other hand, if abortion were to become illegal (not highly unlikely), then presumably the birth frequency of Down syndrome would increase. Limiting access to good medical care (unfortunately also not highly unlikely in the US) could lower the overall prevalence of Down syndrome because of reduced survival.

Current trends suggest that, for the immediate future, prenatal screening will continue to reduce the birth prevalence of Down syndrome. It is becoming increasingly easier for women to undergo prenatal screening and more difficult to just say no. This is due to aggressive marketing by commercial labs of “newer, better, bigger, cheaper” screening tests like NIPT; the dearth of time and resources devoted to unbiased education about Down syndrome and the pros and cons of screening tests; inequitable social distribution of medical resources and social support; and the rarity of long, difficult discussions between pregnant women/couples and their providers about whether they should even enter the prenatal screening cascade to begin with. It also does not help matters that the current US President lacks any moral decency and takes pleasure in mocking people with disabilities.

Although I am a strong supporter of women’s reproductive rights and well-informed, gut-wrenching decisions to terminate a pregnancy, it is becoming increasingly difficult to provide ethical justification for further expansion of prenatal screening, or expanded carrier screening for that matter. This is something that society needs to address but particularly genetic counselors because we are in the thick of it.

As I have previously argued, almost no research has been conducted that has tried to demonstrate whether prenatal screening can improve the medical, social, and emotional lives of people with disabilities and their families. Some women undergo prenatal screening because they think it will prepare them for raising a child with Down syndrome, but we really can’t tell them if screening does help or if it is worth their emotional and psychological investment. Carrying out such research is critical. If we can demonstrate broader benefit of prenatal screening, then we can open up a dialogue with the disability community rather than continue the shouting matches, and offer greater and more equitable justification for NIPT and other screening technologies.

Or we can continue shouting at or dismissing one another.

 

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Euphemisms, Chucklers, Pet Peeves, And Wincers: Thoughts On Our Professional Vocabulary

Words are the clothes thoughts wear.

– Samuel Beckett

I struggle with words. I struggle when I counsel patients to find just the right words to explain genetic complexity while also trying to engage them in a counseling relationship. I sometimes catch myself silently groaning at the stream of what sounds like the absolutely wrong choice of words pouring out of my mouth. I wind up feeling like the voice of the parents in those Charlie Brown cartoon specials; just Wah-Wah-Wah, nonsense utterances that have no meaning or relevance to the central characters. I struggle to understand the psychological meaning of the words patients use to express their thoughts, fears, anxieties, understandings, and misunderstandings. I agonize over these blog postings, repeatedly re-working them until they have the right tone and tenor but still I always feel slightly dissatisfied with some detail of the never-quite-finished product. A close friend says that for him the wrong word is like a flat note in a musical composition. One jarring note and it takes a while for your ear to re-adjust.

So yes, I confess that I am overly obsessed with words. It is yet one more of those Devil-and-Angel aspects of my personality. Good and bad must co-exist else neither exists at all. That obsession is the impetus for this blog posting – exploring the deeper meanings, ramifications, and implications of the vocabulary of genetics, medicine, and reproduction.

I start with words that make me wince. I have previously written about products of conception, habitual aborter, and mutant. Let me add incompetent cervix and birth defect to that list. Even though these words are not used with dark intent, they say a lot about underlying unconscious attitudes and biases. Incompetent cervix is clearly a term created by men for women. Would a man who has difficulty attaining or maintaining an erection ever be said to have an incompetent penis? Birth defect is no better, though in all honesty I catch myself using it from time to time. Just another malfunctioning piece of machinery, a mistake, a reject, an inferior product of conception. And don’t get me started on crack babies. These are all judgmental and harmful words, weaponized to induce blame, shame, and guilt.

In some contexts, benign words can be manipulative, such as high risk. Every patient has a unique and flexible definition of high. But when professionals say high risk it can create a disproportional sense of worry and anxiety. For example, it is often said women 35 and older are at high risk of having a baby with Down syndrome. You can try to soften that by saying higher but the patient mostly hears the high part of that word. In fact, though, the chance that a 38-year-old woman will not have a baby with an aneuploidy is 99%. Those are pretty good odds in my book. But the presumably unconscious and unstated attitude of health care providers is that aneuploidy is an unacceptable outcome – a risk, not a probability – when they show a woman a graph or table displaying age related odds without an objective reference point to put the numbers in context. That is a lot scarier than reframing it as barely 1%, as well as sounding like an unstated scolding – “Well, if you hadn’t waited so long to have a baby, you wouldn’t have this problem.”

Some words are euphemisms. Family balancing – using reproductive technologies to choose the sex of a baby for non-medical reasons – comes to mind. It is fine and normal to want a baby of a particular gender. There are also different cultural imperatives and norms, and complicated psychological reasons why a particular gender is strongly desired.Calling it balancing glosses over the darker implications of reinforcing, and profiting from, sexism. And it implies that a family of all girls, all boys, or varying gender mixes might be out of balance.

Family balancing is a cousin to gender swaying. At first I honestly thought it referred to someone like David Bowie who seemed to fluidly float along the gender spectrum. As I have come to learn, gender swaying describes the practice of trying to increase the odds of having a baby of a particular gender by using folk methods and pseudoscientific techniques, like ovulation timing, cervical PH, and, my personal favorite, positive and negative ions in the air that can be affected by artificial lighting (just why would artificial lighting be found, uh, “down there”?). Somehow it seems more ethically innocuous than family balancing, maybe because the success rate is usually not statistically significantly greater than 50%. But family balancing and gender swaying are on the same moral spectrum. Another euphemistic term is fetal reduction, which neutrally smooths over the rougher ethical edges when a medical procedure transforms a quadruplet pregnancy into a twin pregnancy.

In genetic counseling, we try to reciprocally engage our patients to make the experience more counseling than lecturing. But there is still an underlying power dynamic that can sneak between the cracks and that can remind the patient who is in charge. An example is when we say that we take a family history. Although it is not how we intend to use the word, taking implies that I have the power to assume ownership of story that belongs to the patient, a story that is deeply personal. And by taking it, I now own this intimate knowledge and transform it into something that I reframe into a medical context that gives me power by “interpreting” it for the patient. The message can be “I know what you think about your family history, but let me tell you what it really means.” Perhaps too this power differential  underlies some of the unease many genetic counselors have about Direct To Consumer genetic testing – it diminishes our gatekeeper role of controlling access to genetic testing.

Along those lines, think of the power relationship implied by medical consultation notes that state that the patient denies a family history of genetic disease or drug use or certain symptoms. Denies? Like they are suspected of lying or a criminal activity, and I am the Grand Inquisitor trying to drag the truth out of them? Were these patients ever expecting the Spanish Inquisition?

Not all of my vocabulary pondering is dark. Some reflect my personal pet peeves on usage. I am not a Language Fascist who tries to enforce arbitrary grammatical rules because, dammit, that’s the right way. On the contrary, I love language for its variety, constant evolution, playfulness, and wonderfully creative adaptability. But a few words rub me the wrong way. Pre-existing condition is an ear-sore for me. How can something be pre- to existing? Either something exists or it doesn’t. They are existing conditions. Of course, this mild upset is nothing compared to the outrage I feel at the pig-headed, uninformed, downright nasty views about pre-existing conditions expressed by the President of the United States and his lackey Director of the Office of Management and Budget, they who are too shameful to be named. Now there’s a pair of bad hombres you’d love to rope with Wonder Woman’s Lasso of Truth. Another “earitation” is when someone writes “The patient was told to return in 3 weeks time.” In that sentence, the word time belongs in the Department of Redundancy Department; the same information is communicated if the word is omitted. For my internal ear, it is a jarring note.

Another, perhaps more justifiable, pet peeve is when an author or speaker says something along the lines of “there was a 500% reduction in disease occurrence following this intervention” or “a five fold reduction in occurrence.” Sorry, just flat out impossible. Nothing can be reduced by more than 100% or 1 fold. After that, it ceases to exist (unless of course it were pre-existing) or it becomes an imaginary number*. If the number of cases of a disease decreases from 500 patients to 100 patients, that is an 80% reduction. Or there are one fifth of the number of cases that occurred prior to the intervention. And I don’t believe I am being a kvetcher here. Accuracy in statistical analysis and interpretation is at the very core of the scientific process and discourse, so it is critical to use the right words to describe research results.

There are some words that make me smile when I hear them, such as Captain Underpants’ arch-nemesis Professor Pippy Pee-Pee Poopypants or HMS Boaty McBoatface (okay, they have nothing to do with genetic counseling but even if your inner mind is not permanently mired like mine in the 8 year old boy phase, these names make you chuckle). Similarly, I smile when I hear surgeons describe large breasts as generous. How nice that someone has generous breasts! It almost sounds like a description of a wet nurse. A long time favorite is Instant Baby Formula, which I first encountered 45 years ago when I was a stock clerk at a Brooklyn grocery store. Just add water, and Voila! You have a baby. What could be simpler? None of the icky bother of 9 months of pregnancy or the agonies of labor.

I would love to hear from the Good Readers of The DNA Exchange about their thoughts on the vocabulary of genetics and medicine. What in our professional lexicon makes you irritated, raises your moral hackles, induces euphemistic groans, or you just enjoy? Given the widespread employment of genetic  counselors in laboratories, is there some new Lab Vocab starting to emerge?

As Raymond Carver once wrote in a NY Times piece, “That’s all we have, finally, the words, and they better be the right ones.” So let us make sure we think carefully about them, choose and use them wisely, never weaponize them, and remember to enjoy them.


  • – Yes, I know that this is not technically an imaginary number. I am just employing poetic license.

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Why Me?

“We tell ourselves stories in order to live.” – Joan Didion

Even after decades of clinical experience I am still struck by the sometimes random and sometimes cruel nature of the occurrence of genetic and congenital conditions. You meet a family with 3 successive children with a profoundly serious recessive condition and the next carrier couple that you see have 6 unaffected children. A grandmother watches her husband, son, and grandchildren die from Li-Fraumeni cancers, and then you encounter a TP53 mutation in a young woman with breast cancer and a family history devoid of other cancers. A gene panel reveals that a woman has dodged a BRCA1 mutation in a pedigree overflowing with breast cancer – but she has a pathogenic APC mutation and not a single relative with colon cancer or polyposis. An adopted woman learns she is pregnant the same day she is contacted for the first time by her biological family and told that her biological father just died of Huntington disease.

We consult the Codex of OMIM or the Oracle of Bayes, and then tell scientific stories of skewed mendelian ratios or stochastic processes (Literal translation: Shit happens), stories as much for ourselves as for our patients. My favorite (non)explanatory story is “a multifactorial combination of genetic and environmental factors.” Come on, please. What human trait is not the result of a combination of genetic and environmental factors? We can wind up committing the original sin of genetic counseling – responding only with cold, meaningless facts to patients’ cris de coeur for comfort, validation and acknowledgment of their emotional states, their quest for a psychologically meaningful understanding and acceptance of their situation, and the need to make sense of their suddenly upturned lives. We should be forgiven though. Genetic counselors are only human and who among us is without sin? None of us were immaculately conceived.**

Patients will fill this void with their own stories. It was that stress in my life. They used to spray insecticide all the time in my neighborhood and now every house on my block has someone with cancer. Then there are the somewhat morally judgmental plaints – I am a vegan, I exercise daily, and put no poisons in my body; my sister eats only fast food, smokes, drinks, and has a new boyfriend every weekend, but I am the one who gets cancer and it’s just not fair. Or it must have been the manufacturing plant down the road with that awful chemical smell (How come no one ever lays the blame on pleasing aromas like cinnamon buns in the oven, freshly roasted coffee, or the sensual curry infused scent of an Indian kitchen?).

If Joseph Campbell was right, mythopoesis is as innate as erythropoiesis. Our minds can’t help but tell stories like our marrow can’t help but make blood. So let me offer my own mythological explanation of the epidemiology and distribution of genetic and congenital disorders – Pedigrus Rex, the god and ruler of pedigrees. Pedigrus is definitely  in the classic Greco-Roman tradition of a powerful god ready to unleash his power at a mere whim or perception of insult, without the slightest thought to consequences. As much Zeus as Trickster.

Pedigrus rex

Sometimes he is benevolent. Let’s see, I will render that woman pregnant after she has given up, exhausted from years of unsuccessful fertility treatments. Sometimes he is terribly unkind (Pedigrus Wrecks?). Hmmm, I think I will give a tetralogy of Fallot to that baby with severe ichthyosis. Hey, why not introduce yet another common mutation in another gene to the Ashkenazim? Sometimes he is astonishingly trivial in his malevolence, like making my pedigree software malfunction after having entered a hugely complex family history. Usually, though, he is emotionally indifferent, just going about his business of indiscriminately sowing the seeds of sadness, joy, shock, and love into the soil of human reproduction. We may try to appease him with sacrifices in our temples or try to understand his motives by consulting seers and prophets in our clinics. Mostly, though, he is beyond comprehension and placation.

This is not to lessen the importance of providing medical and scientific explanations. Many patients want technical information and often that is why they come to us. The beam of knowledge sheds some light for them but does not fully illuminate. They will integrate the scientific story into their own narrative – but on their own terms. It is only part of what they are seeking. Our duty to patients is not discharged once we have given them a recurrence risk or a name to their child’s condition. We need to help them create a psychologically meaningful narrative, a life story, that helps them cope and adapt to their situations, to grow and move on.

The Greek tragedies teach us that we have the ability transform sadness into love, shock into acceptance, fragility into strength, denial into hope. Suffering (pathos) turns into recognition (anagnorisis) and reversal (peripeteia). Humanity trumps divinity by telling stories that work emotional miracles. We can all be greater than gods.

“Mythology, in other words, is psychology misread as biography, history, and cosmology.”
― Joseph Campbell, The Hero With a Thousand Faces

Thanks to Emily Singh for help with the graphics.


** Let me digress here and correct a common “mythconception” about the term Immaculate Conception. Most people use the term to describe a conception that occurred without the benefit of sexual intercourse. This is quite incorrect; this is confusing Immaculate Conception with Divine Conception. Immaculate Conception refers to Mary, the mother of Jesus, and not to the conception of Jesus. In Roman Catholic doctrine, Mary, who was the product of conjugal relations between her parents Joachim and Anne after years of infertility, was the only human ever conceived without Original Sin on her soul, i.e., she was immaculately conceived. Jesus, on the other hand, was the product of Divine Conception by the Holy Spirit. He could not have been conceived in the usual style because that would have tainted him with Original Sin, a trait he would have inherited from Mary’ s husband Joseph. Mary learned of her pregnancy at The Annunciation, traditionally 9 months before Christmas on March 25th, when the Angel Gabriel announced to her that “the Holy Spirit would come upon thee” resulting in the miracle of divine conception in Mary’s virginal womb that was unblemished by sin or sex, and without Joseph’s, er, assistance (Joseph had his own visit from an angel who sort of explained the situation to him. So you  might understand why Joseph was deserving of sainthood.).

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Barriers or Filters?

 

Both good and bad can be said about Direct to Consumer (DTC) genetic testing. Some of the tests offered are probably better labeled Dreck To Consumer. Please, somebody, issue a cease and desist order for MTHFR testing. Or better yet, make it a criminal offense, punishable by sentencing to hard time at the Clockwork Orange Folic Acid Supplementation Rehabilitation and Penal Colony.

On the other hand, I am betting that established labs that currently offer clinically useful genetic testing will be migrating toward a greater presence in some form in the DTC market. This trend will be driven, by among other things, the demand on the part of some patients because of the convenience factor, the increasing uptake of BRCA testing by unaffected women, and by the potential income source it would create for labs. Whether clinicians like it or not, some form of DTC testing will probably play an increasing role in patient care in the near future. We will need to adapt to it, even if it makes some of us feel uneasy. My prediction is that we will initially see the most significant inroads in the area of DTC germline testing for cancer predisposition gene panels that include BRCA, Lynch, and their kindred.

Another  factor that could drive DTC testing is that genetic counselors are sometimes viewed by clinicians, labs, and consumers as barriers to genetic testing. For patients, just finding the time in their busy lives for an hour long appointment and verifying insurance coverage for the consultation is no mean feat. Then there is the genetic counseling ethos of nondirectiveness and genetic counselors’ obsessive urge to (over?)educate patients, which can result in some patients coming out of the session saying No Thank You to genetic testing for now, much to the chagrin of their referring care providers. Not to mention the lack of genetic counseling manpower in some parts of the country. From this perspective, you start to understand why some critics claim there can be a reduced uptake of genetic testing when a genetic counselor is an intermediary between patient and laboratory.

Genetic counselors might cringe at the thought of patients entering the genetic testing pathway without having worked through the emotional implications, and possibly partially blind to the clinical and personal implications of positive, negative, and uncertain results. We somewhat paternalistically view ourselves as guardians of our patients’ medical and emotional well being. While genetic testing may be important for patients, at least for unaffected patients genetic testing is rarely an urgent matter. It can take place today, next week, a few months, next year, or at some point in the vague future. Perhaps that is not so terrible because a test result delivered at the wrong moment might backfire by causing the patient to go into a psychological tailspin and possibly wind up avoiding risk reducing and screening strategies. In this way, genetic counselors are more like filters than barriers, helping ensure that nobody takes a deep dive into their gene pool without first pausing and taking a deep breath.

This response may be partially and subconsciously influenced by the fact that our jobs depend on the steady stream of patients seeking genetic testing. DTC also takes away some of the “gatekeeper” power inherent in our positions. Conflict of interest affects us in ways that can make us too uncomfortable to acknowledge that it might it shape our beliefs and attitudes.

Enter DTC into this drama, stage right. If you are a patient who has a few hundred bucks to spare, you can avoid carving a chunk of precious time out of your busy schedule to set up a genetic counseling appointment (and maybe 2 or 3 appointments, depending on the provider’s policy of requiring separate appointments for counseling, test, and results disclosure), avoid those incomprehensible (non)explanations of benefits from health insurers, and with saliva testing skip the unpleasantness of a blood draw (although saliva collection has its own icky issues). Those forward-thinking online genetic counseling services that are unaffiliated with specific labs may help mitigate some of these perceived barriers, but maybe not enough for the majority of patients. DTC labs make it pretty easy to sign up for genetic testing, no muss, no fuss, never needs ironing. If I am honest with myself, in some situations – and maybe more often than I am willing to acknowledge – the “hassles” of genetic counseling may very well serve to discourage a goodly number of patients from undergoing genetic testing.

One concern about DTC is the way that labs may try to portray their tests to patients. Labs typically strive to act in patients’ best interests and try to make sure that patients get the genetic testing they need. By and large I find them to be just as committed as I am to providing excellent patient care. But at the end of the day they are businesses, and even if they have noble aspirations, it is in their best interests for as many patients as possible to undergo genetic testing. This can subtly influence their advertising under the rubrics of patient education and patient empowerment.

The best example I can think of to illustrate this point is the websites of many labs that offer cancer genetic testing, DTC or otherwise, which often cite the high end of disease risks in hereditary cancer syndromes. Labs aren’t lying to patients when they quote 80-90% lifetime breast cancer risks or whatever. But it certainly makes their genetic tests look more clinically critical than, say, the 40-50% risks found in some studies. It’s not that the 40-50% risk is necessarily closer to the “true” risk than 80-90%. The point is that there a range of risk estimates out there and which risks one chooses to present can be influenced by many factors.

Here is one lesson I have learned from ~34 years of genetic counseling with about a jillion patients: Nobody undergoes genetic testing until they are emotionally ready. Sometimes that readiness is thrust upon the patient, such as when a patient is diagnosed with cancer and has to make treatment choices fairly quickly. But for unaffected patients, some emotional triggering event(s) needs to occur before they make a genetic counseling appointment. Examples of triggering events might include reaching an age when the patient’s own parent was diagnosed with cancer or when their own child reaches the age the patient was when the patient’s parent was diagnosed; having a false positive “scare” on a mammogram; a recent cancer diagnosis in a loved one; a media celebrity such as Angelina Jolie sharing a personal cancer story; reaching a certain stage in life where, as one patient put it, “It was time to start acting like an adult” (which I suspect for many people is the incipient stages of facing their own mortality); having a grandchild; or gazing at your child one day and realizing that you might want to be around for your kindergartener’s college graduation.

If my observation about what leads patients to genetic testing is correct, it will be interesting to see if affordable, convenient, DTC genetic testing will itself become the trigger event that nudges patients into undergoing genetic testing. Would this be good or bad? Will we see a rapid proliferation of genetic testing for hereditary cancer or other syndromes if DTC testing becomes widely available? Will this translate into clinical gains that are also economically cost effective, such as increased uptake of risk-reducing surgery and high risk screening? Who will watchdog labs to assure that they offer a quality, uniform, and trustworthy product that patients can depend on without first doing in depth research about depth of coverage, variant calls, and the other arcana of genetic testing? If recent calls for cancer genetic testing for essentially everyone, such as the proposal by Dr. Mary-Claire King or Canada’s Screen Project, become widely embraced, will DTC be the most efficient way to deliver the service? Will life insurers start requiring genetic testing before a consumer is eligible for a policy? How often will untrained care providers and patients misinterpret test results? Will it turn out that genetic counselors are barriers to genetic testing or are they filters who help ensure that the appropriate patients get the appropriate testing at the appropriate time in their lives? Will genetic counselors wind up largely becoming, as I have predicted for years, phenotype counselors who meet with patients after genetic testing?

Nobody knows the answer to these questions, although a lack of data has never been a barrier to strong opinions. This is the time to plan research studies that can help address them. The genetic counseling profession needs to continuously adapt and evolve. But it needs to do so without losing its soul.

 

Thanks again to Emily Singh for help with realizing the graphics.

 

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Are We Ready For This?

Recent advances in genetic testing technology have us poised on the brink of a new paradigm of prenatal diagnosis – prenatal screening for all genetic and chromosomal conditions. Okay, not all disorders, but lots. Non-invasive Prenatal Testing (NIPT), whole exome sequencing, and expanded carrier screening are close to being available and affordable to a large proportion of the population. This is the culmination of a trend that began with the introduction of amniocentesis in the late 1960s, followed by ultrasonography, maternal serum screening, microarrays, and cell free placental DNA in maternal serum. From a strictly technical standpoint, each technology, while far from perfect, was an improvement on its predecessors in terms of accuracy, detection, false positive rates, and the range of  detectable genetic conditions.

On the surface, this sounds like progress, and it is, in many ways. These technologies can contribute to the reduction of the incidence genetic conditions, some of which are pretty serious, a long-standing goal of medical genetics since its inception, as Nathaniel Comfort has pointed out. But technological advances often outstrip the ethical and social means with which to appropriately assess, modify, and utilize them in fair, just, and meaningful ways. So I ask these questions of the sage and thoughtful readers of The DNA Exchange: Just because we can perform prenatal screening for nearly everything genetic, should we? Who should be making this decision?

There are many competing and intertwined narratives about the history of prenatal diagnosis. Let me offer one such narrative to provide ethical and historical angles. During the 1970s and early 1980s, amniocentesis was primarily offered to women of “advanced maternal age” because of the well-documented increase in the incidence of trisomy with maternal age. At the time, in the US women 35 and older represented about 5% of the pregnant population, and this group accounted for about 20% of pregnancies with Down syndrome (this statistic has since changed considerably). While such a policy could be viewed as discriminatory and prejudicial against people with disabilities, the goal of the policy did not seem to be the elimination of genetic disability. Rather, the effect and likely the intent of the policy was to level the reproductive playing field for “older” mothers. During the 1970s, women made great strides in expanding their social and economic opportunities and in taking some measure of control over their reproductive lives with birth control and the availability of safe, legal abortion. Women could now readily attend most colleges and graduate schools, had more career opportunities, and did not feel as much social pressure to retire to motherhood after high school. However, one of the perceived obstacles for delayed childbearing was the greater risk of Down syndrome and other trisomies. Amniocentesis removed this perceived obstacle and consequently women felt freer to delay childbearing until such time as they felt that they and their partners were ready.

Over the decades, mission creep worked its way into prenatal screening. With the gradual incorporation of ultrasound and maternal serum screening into most pregnancies, regardless of maternal age, the detection rate for Down syndrome increased, and critics of prenatal diagnosis raised the specter of the theoretical elimination of all people with Down syndrome. While such an outcome never seemed likely for a variety of social, cultural, individual, and economic reasons, that could be viewed as the intent of prenatal screening. But still, aneuploidy represents only a small portion of all genetic and congenital disorders.

But it is a qualitatively different ethical story with universal NIPT and the expanding number of conditions it can screen for, the prospect of carrier screening for hundreds of genetic conditions for all couples, and talk of whole exome screening of fetuses. That is making quite a profound statement to and about people with a wide range of physical and developmental abilities.

We tacitly assume that the majority of pregnant women want such screening at the same time that we offer it to them. Many patients will  assume that because we are offering it, it must be a good thing. Because genetic counselors’ jobs can depend on the offer and uptake of such services, it affects our views and actions in ways that we often cannot fully appreciate or grasp. To some extent, we offer new testing because labs are offering it and because genetic counselors tend to be early adopters of new genetic tests. As much as we like to think that we are objective assessors of genetic technology who always put the best interests of patients first, the complicated human psyche makes for a messier reality. Our perspectives are distorted by being in the center of the storm. Go ahead and disagree with me if you want, but you are by and large wrong. That’s not me trying to sound superior; motivated blindness is a basic foundational principal of human psychology.

Psychological complexity aside, think of this. The medical profession is already doing a less than stellar job of presenting a realistic and unbiased picture of Down syndrome to parents. Remember, too, that more and more prenatal genetic testing happens without the involvement of a board certified genetic counselor and that parents are often not educated about these conditions until after they have received an abnormal test result. Not exactly the best time to seek out and weigh complicated information. Add a few hundred more conditions less common and familiar than Down syndrome, and you can see the makings of a goddamn mess.

So can there ever be an ethical justification for universal prenatal screening of (theoretically) all genetic and chromosomal diseases? Let me offer some suggestions that could serve as a starting point to address this question. One can argue that this framework or one like it should have been in place decades ago. I agree, it should have. I recognize that for people who are opposed to termination of pregnancy under any condition or for some of the staunchest disability advocates, prenatal screening will never be acceptable unless it somehow improves the lives of people with different abilities and their families. But I ask all sides to at least hear me out.

First, many parties should be involved in the discussion about wide scale prenatal testing, à la Cyprus and thalassemia screening. Prospective users, clinicians, labs, ethicists, religious leaders, legal experts, legislators, and most especially the community of people who are affected directly by the conditions in question (let me add “and others” since no doubt I am forgetting some important stakeholders). You will never get everyone to agree on all of the details, but there should be at least broad consensus about the most critical issues among the majority.

Second, more resources need to be devoted to improving the lives of people with genetic conditions and their families. Every newborn should  be able to live full, rewarding, loving, and enjoyable lives as much as humanly possible. This involves large-scale medical, technological, and social innovations and changes. Improving the social attitudes toward disability is a long, slow, frustrating journey but that should not deter us.

Third, related to the above, prenatal genetic testing should also offer some benefit people with the conditions in questions and their families, other than letting them have the same option as everyone else to terminate pregnancies. Right now, people with disabilities and their families get essentially zero benefit from prenatal screening. Or more accurately, very little research has been done to show any benefits.

Fourth, any new technology or test needs to be vetted by those who do not have a vested professional, financial, or personal interest in the technology or test. Intellectual, research, and financial conflicts of interest have ways of distorting our views in subtle ways that we are incapable of appreciating. This is extraordinarily difficult for us to understand and acknowledge (vide supra motivated blindness).

Fifth, better resources need to be developed for parents to become educated about the medical implications of genetic diagnoses, the range of developmental outcomes, the resources available to manage the condition, and the impact on families, particularly in lower socio-economic populations.

Sixth, this information needs to be provided to parents before they decide to enter the cascade of prenatal screening, not after they receive an abnormal test result. Parents have to carefully decide which if any condition(s) is important to their reproductive and family planning.

If all of these recommendations are in place, this will allow parents to make informed choices about whether or not they wish to go down the prenatal screening pathway and for which conditions. For parents who would never consider a termination under any conditions, they should have the option of screening only for those conditions for which prenatal knowledge can help the child and family, with better medical, psychological, or adaptational outcomes. For parents who have carefully weighed these issues and feel that there are certain conditions that they will choose to avoid if they can, then they should be supported in their decisions with safe, legal, and non-judgmental abortion services. For parents who are not interested in prenatal screening, they should be supported in their decision rather than being made to feel like they are sub-standard parents.

We can ignore my plea, just sit back and see what happens. But this would be a big mistake. Although genetic counselors obviously cannot address this issue by themselves, we are in the ideal position to take the lead in organizing, coordinating, and spearheading the discussion. We owe it to ourselves and to our patients.

 

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