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Genetic Testing at Birth-Is it too Early?

 

UntitledI recently saw a 50-something year old man for a cancer genetic counseling session. When we got to the concept that mutations in the BRCA genes may increase someone’s risk to develop breast and/or ovarian cancer, he was amazed. He said to me, “If the technology exists for someone to know his or her genetic risk to develop cancer, and there may be something to do to reduce these risks, wouldn’t it make sense to learn this information when someone is young?”

I was pleased to hear this question since it proved to me that he was really paying attention, and although he didn’t realize it, he touched on an issue which is very timely in the world of genetics and ethics.  The issue of whole genome sequencing (reading through all of someone’s genes to look for variation) is a hot topic in genetics. Currently, the reasons we might order any genetic testing are if there is an underlying medical issue for the individual, a family history of an issue, or if someone is from an ethnic group that has known founder mutations for particular diseases. When we do this sort of testing, we are looking for relevant mutations in one or more genes or chromosomes.

But recently, scientists have introduced the notion of testing the entire genome of all newborns-even those who are seemingly healthy. (Note: I am not talking about the Newborn Screening panel—AKA “heel stick test” or “PKU test”—which is mandatory in the United States, and tests for about 30-55 diseases, depending on the state).  And to make things sound even more exciting, the first baby to ever have his genome sequenced prenatally was born last month in California!

Back in November 2012, Nicole blogged about her discomfort of whole genome testing, as opposed to targeting the genetic testing to the medical issue at hand.  When we do whole genome sequencing, we are going to learn about that person’s traits, carrier status, predispositions to childhood and adult-onset disease,  and we may even diagnose a disease, possibly presymptomatically (ie- before the person even starts exhibiting symptoms). Some might think that all this information is great, since it’s better to know now than to be surprised when it happens.

Others believe that this type of testing for newborns is unethical. Here are a couple of reasons why:

1-The genes belong to the child, not the parents. Shouldn’t it be up to that child to make this decision?

2- Say we learn that the child is genetically predisposed to having Parkinson’s disease. This most likely will not happen for another 50 or so years, and it may never happen at all.  Does he want to be that person who is just waiting to get sick? This may cause anxiety, stigma, and may change the way his family and friends perceives him.

3- If someone learns from a young age that he has a genetic predisposition to a condition, he may ignore the other (non-genetic) risk factors. For example, let’s say someone learns that he has a genetic variant that leads to a high chance of developing diabetes. He may not try to eat healthy foods or exercise or go for checkups because he believes that his genes alone will determine his risk for diabetes. This is what we call “genetic determinism.”

I told my patient that he did not realize that he had opened up a can of worms and that we would need a whole new session just to discuss his question. But he definitely got me thinking.

 

Updating Your Carrier Screening

update carrier screening croppedWhen I was at a recent sisterhood event at my synagogue, a friend of mine approached me to ask if she should “do her genetic testing again” since she and her husband were first tested in 2007 and have not been tested since. I answered with an emphatic “YES!” I appreciated that she knew to even ask this question, but our conversation got me thinking. Do other people know that new diseases are regularly being added to the Ashkenazi  Jewish panel?

The best time to get screened is well before a pregnancy. Since the 1980s when Tay-Sachs testing was introduced to the Ashkenazi Jewish world, there has been much progress in the realm of genetic testing. Currently, we screen for about 18 diseases that are common in this population. And testing for Sephardi and Mizrahi Jews as well as Jews of mixed ancestry has become more commonplace. But someone who was tested in 2001, for example, and was negative, is not “in the clear” since many more diseases have been added to the panel since then.

Many people ask me, “If I am already married, why should I bother updating my testing? It will only make me more anxious as I continue having children.” My response is that I’d rather find out that you are both carriers of the same genetic disorder by doing a blood test, rather than finding out after you have an affected child. There are other options besides for stopping childbearing, rolling the dice with each pregnancy, and breaking up! Other family planning options include testing the fetus early in the pregnancy, using an egg or sperm donor, and adoption. In-vitro fertilization with pre-implantation genetic diagnosis (PGD) is another great alternative for couples who want to know their child’s genetic status before it is even in-utero. By doing genetic testing this early on, a couple will avoid getting pregnant with an affected embryo and will circumvent any ethical or issues related to Jewish law that may arise.  Robin’s Story, a short public service announcement on MyJewishGeneticHealth.com, will open your eyes as to the importance of updating your screening and learning your options. And be sure to register to watch Dr. Lieman’s longer webinar about PGD and Chani’s lesson about preconception carrier screening!

Finally, while testing for diseases that are common in specific populations is currently recommended by professional genetics groups, there are labs who are now offering screening for many more diseases. These expanded carrier screening panels claim to be “one size fits all” and are marketed to all ethnicities, but a negative result on a broader screening does not fully eliminate the risk of having a child affected with one of the tested disorders, it only reduces the risk. Furthermore, expanded carrier screening does not cover all diseases that could affect offspring.

I wish I could go into every synagogue, preschool, sisterhood, and other places where women in their childbearing years hang out to remind them to update their carrier screening! But since that is impossible, please take the time to mention it to your family and friends and help me spread the message. Let’s avoid heartache together!

Genetic Screening Sunday

carrier screening PSAMost of my Sundays involve errands, and then some dedicated time to relaxing and recharging before the upcoming week. This past Sunday I spent ~8 hours at a screening event that we ran at YU, open to Yeshiva College and Stern College students and alumni, and community members in Washington Heights. Registration opened ~3 weeks ago, and we were almost at capacity within days. We ended up screening ~140 individuals (not too shabby if you ask me!).

Screening events such as this one are really great, but also very challenging. They are great because it enables a large audience to benefit and pursue carrier screening in a convenient and centralized location. Screening events are challenging because of all the planning, coordination, and logistics which are involved in counseling and testing literally hundreds of people at a time.

One of the things which made this event run so smoothly is a new video we created as a tool to teach people about Jewish carrier screening. We decided to make this short video around the same time that I filmed the video for our new GeneSights lesson about Preconception Carrier Screening. Some of the more amusing parts of the day were all of the “You’re the woman from the video!” comments that I got. You can access the full GeneSights lesson by signing up and signing in here.

Even though it was a very long day, luckily, we had a ton of help! Special thanks to all our physicians, genetic counselors and genetics fellows, volunteers from the YU Medical Ethics Society, volunteer genetic counseling students, and our phlebotomists! (Anna, Ariella, Aryeh, Avi, Barrie, Carol, Chana, Chris, Emily, Jon, Mickey, Pauline, Sam, Sara Malka, Sara Malka [yup there were 2], Shirley, Susan, Tehilla, Temima, Yocheved, and Yosef). We could not have done it without you! A big thanks to Estie Rose, our genetic counselor who organized the event. The day went so smoothly, and in my opinion, was a big success. Now it’s time to wait for the results and begin the never ending process of follow up. Since 1 in 3 Ashkenazi Jews is a carrier for one of the conditions we screen for, I guess we’ll be expecting ~47 carriers from this screening event. That’s a lot of follow up!

If you missed the event but would still like to be screened, check out these great instructions on how!

Back to the Swing of Things

swingWelcome back! Summer vacations have come to an end, we’ve passed the Labor Day mark, school is back in session, and we’ve reached the never ending season of Jewish holidays. We’re finally (almost) back to regular swing of things.

Here at the Program for Jewish Genetic Health, we’re also really excited about kicking off the New Year. We recently reflected on some of the projects we’ve been working on, and have realized that we have quite a bit to be proud of!

We’ve been trying to spread information and education about genetics and how it impacts the Jewish community. This past January, Estie wrote an article for the Jewish Press  talking about the importance of preconception carrier screening, and just this past August, she wrote another article explaining the importance and utility of genetic counseling. I wrote an article which appeared in the Jewish Press about BRCA related hereditary cancers and the usefulness of genetic testing.

Over the past year, we launched our GeneSights online education platform, as well as three lessons; Genetics 101, Hereditary Breast and Ovarian Cancer (BRCA1 and BRCA1), and Inflammatory Bowel Disease: Crohn’s Disease and Ulcerative Colitis. Our next lesson:  Preconception Carrier Screening: Tay Sachs and many other diseases, has already been filmed, and we’re planning to launch it this October or November!

We’ve given numerous in-person talks and educational events in and around the NY area as well as in Memphis, TN, Chicago, IL, and Phoenix, AZ. In addition to community education, we’ve focused on educating Rabbis, community leaders, and healthcare providers about some of these important issues. We have a number of new educational events scheduled and in the works for the upcoming year!

Aside from being able to help coordinate carrier screening at our clinical offices at Montefiore, we’ve also held a community screen this year at Columbia University. Our annual community screen for Stern College, YU, and the Mount Sinai Washington Heights community is coming up soon, and will be on November 10th, 2013 (hope to see you there!).

To me, the fall has always felt like a time of new beginnings. As I child, I loved going back to school, learning new things, and getting a fresh new start. Here at the Program for Jewish Genetic Health we have lots of new and exciting projects in the works. We’re hoping that this upcoming year will be a fantastic one for our PJGH family, and for yours.

(And to get back on my soap-box for one more minute, as I’ve done now on numerous occasions, I’ll remind you to find out more about your family medical history. If you’ll be with family over the holidays, use this opportunity to speak with them and gather this important and potentially lifesaving information!)

A Plea for Being Prepared

I recently was introduced to a young woman at a party.When she heard that I am a genetic counselor, she said, “What a coincidence, I need to speak with a genetics expert! You see, I am engaged and my fiancé was tested for Tay-Sachs but I think we may need to do some more genetic testing before we get married.” Feeling good that she met me at the right time, I told her to set up an appointment at our office. “Great,” she replied, “Because we are getting married in 2 weeks and I would like to know the results by the wedding date. “ I tried to dissuade the young woman from getting tested now, since the results would not be back in time for the wedding, and she did not need the extra stress.  I told her to enjoy her wedding and contact me before contemplating her first pregnancy. “But we want to get pregnant the night of the wedding,” she replied.

This was not the first time I have heard of this.  In some sects of Orthodox Judaism and other religions, couples decide against contraception; they believe that family planning is up to God.  And sometimes, even couples who do use methods of birth control may be surprised to get pregnant.  My point is, whether or not you take contraceptive measures, there is always a chance you could get pregnant.   And this could have added implications if the couple is at increased risk for offspring with a genetic disease.

I am not trying to scare you; I am merely trying to set the stage for my position on carrier screening.  If a couple finds out that they are both carriers of a recessive disease such as Tay- Sachs, this means that there is a 1 in4 (or 25%) chance of having an affected child with each pregnancy. Wouldn’t it be better for such a couple to know that they are at risk before getting pregnant? Instead of achieving a pregnancy naturally and taking that 1 in 4 chance, a carrier couple may decide to do in vitro fertilization with pre-implantation genetic diagnosis (what genetics people call “IVF with PGD”). Other couples may opt to use an egg or sperm donor (who is not a carrier of the same disease), and others might decide to adopt or not have children at all. My point is that if a couple knows before getting pregnant, they have more reproductive options available to them.

And what about those couples who do not plan their pregnancies to the day? For instance, consider the woman who decides against using contraception on her wedding night, or the couple whose methods do not do the trick. Those people (ie, could be anyone!) ought to know their carrier status sooner rather than later. It’s always better to be prepared than to find out during a pregnancy when difficult decisions may be on the table, or even later with the birth of an affected child.  So remember that you cannot plan everything in life-but for those things that you DO have control over (like going to get screened), why wait?

Click here for a short PSA on the importance of getting tested

Are we sure we really want to go there?

DNA code analysisAs an Ashkenazi Jew and someone who was pregnant several times in the late 1990s and early 2000s, I witnessed, from the perspective of a patient, the stepwise increase in the number of Jewish genetic diseases for which carrier testing was available.  When I moved into this scientific realm professionally in 2006, I realized that that was only the tip of the iceberg.  What had started out as population testing for one disease only (Tay-Sachs) in the 1970s rapidly advanced gene-by-gene, to the point where now we readily can test for carrier status for at least 18 of the so-called “Ashkenazi Jewish genetic diseases.”

Until recently, testing was performed in a gene by gene manner, resulting in additive costs that reached the thousands of dollars.  Fortunately, breakthroughs in technology have led to significant progress in reducing the costs associated with screening for many diseases at the same time.   Now, a single DNA sample can be assessed on a “chip” or an “array” that simultaneously can survey many mutations in many disease genes .  If a mutation is detected by the array, then that individual is said to be a “carrier” of the associated genetic disease.  Remember, carriers themselves do not and will not exhibit symptoms of that disease, but offspring of carrier couples are at risk to be affected.

Okay, now here is where the “are we sure we really want to go there” question comes into play.  Right now, we are still testing for the common mutations in the relevant disease genes with these “targeted” arrays.  But there are other rarer mutations in those same genes that have been described to be disease-associated that are not being assessed routinely. So, some carriers are being missed.    If we wanted to look at each disease gene in its entirety, we could instead be using a technology called gene sequencing.  With gene sequencing, each position in the gene is “read” and then cross-compared to the normal sequence.  Many companies and laboratories are thinking about/developing sequencing platforms for the purpose of carrier identification, with the goal of missing fewer carriers.

So what’s the downside? The downside is that we will not only pick up the common+rarer disease mutations, but we will also pick up changes that we cannot interpret properly because we have not seen them before (these changes are called “variants of unknown significance”).  They could be disease-causing in offspring of carrier couples, but alternatively they could be benign.  If we as professionals can’t interpret these properly, what do we tell the patients?

And you know what makes me even more anxious? The alternative concept of sequencing ALL of someone’s genes (their genome) for carrier identification, as opposed to just focusing the sequencing on a targeted subset of genes, such as the subset that causes the Ashkenazi Jewish diseases.  In that scenario, not only will we be grappling with the variants of unknown clinical significance, but also with findings throughout the genome that are incidental/unanticipated. These findings could include mutations that lead to adult-onset disease in the carriers themselves, some of which diseases have no treatments or cures.

Only time will tell where the field is heading, and advances in technology coupled with decreasing costs may be the ultimate drivers here.  I think we should pause and think about how vast the ocean is before taking the plunge.

Thinking Outside the Lines


A few weeks ago, Emily, one of my fellow genetic counselors, saw an Ashkenazi Jewish young woman and her mother for counseling. The reason for their visit was because the mother has a BRCA mutation, which means that she carries a genetic mutation which dramatically increases her risk to develop breast and ovarian cancer. It also means that each of her children has a 50% risk of inheriting the same mutation.

As in any genetic counseling session, Emily took a detailed family history. Her questioning led her to learn some new facts about the young woman: she was only half Ashkenazi, and she and her husband had already done some carrier screening for common diseases in the Ashkenazi population that could affect offspring a few years earlier, and were found to be genetically ‘compatible.’  Emily recommended that she update her panel, despite her only being half Ashkenazi, since she was not tested for the whole battery of tests that is available today. The thought of updating had never crossed her mind. The young woman also had BRCA testing on that day, which at the time, was more anxiety-provoking since its potential results carried more ramifications to her own health.

About 2 weeks later, the results were in. It turns out she was a carrier for 3 ”Ashkenazi Jewish” diseases that she was not tested for earlier! A triple carrier! Had Emily not taken the time to take the family history and think about things that were beyond what the patient came to talk about, this may have not been picked up. This story has a happy ending –the young woman was negative for the BRCA mutation (phew!) and her husband tested negative for all 3 diseases.  But unfortunately it does not always end this well.

Emily’s story makes me want to remind you that genetic information can be difficult to sort through. That is why I am encouraging you to have a genetic counselor explain it all in English and make sure all the proper testing is ordered.  Thinking outside the lines comes with proper training and therefore, if you have any concerns about your genetic health, I strongly encourage you to seek professional help in this realm. You never know.

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