Cobie S. Whitten, PhD.

“This is such an exciting time in “personalized medicine” – there is a vast amount of genetic information potentially available to each of us. At best, the information can inform individual and familial decisions, reduce disease risk, and empower healthcare consumers. But as with any burgeoning field, there are significant potential risks. You want objective, non-profit driven experts to partner with throughout the process. Genetic Support Foundation, an independent nonprofit organization, is a trusted leader in the field offering objective and up-to-date genetic services.”

— Cobie S. Whitten, PhD., Olympia, Washington

The Changing Landscape of Genetic Counseling

The landscape of the genetic counselor workforce has shifted dramatically in recent years, in large part due to new opportunities for genetic counselors in genetic testing laboratory settings.  According to the Professional Status Survey conducted by the National Society of Genetic Counselors, the number of genetic counselors who report a laboratory as their primary work setting has doubled in the past 4 years and nearly tripled in the past 10, with 21% of genetic counselors reporting a laboratory setting as their primary workplace in 2016.  And this likely under-represents the percentage of genetic counselor who are employed by laboratories, as many who work for labs but see patients in clinics likely report their primary work setting as clinical.  


In an analysis of genetic counselors licensed in the state of Washington (presented at the NSGC meeting in 2016) we noted that 42% of genetic counselors were employed by commercial laboratories in 2015 as compared 22% in 2011.  At the same time, the percentage of genetic counselors licensed in Washington state in clinical positions decreased  from 60% in 2011 to 42% in 2015.  


While genetic counselors play important roles in laboratory settings, what does this shift in employment mean for the field of genetic counseling?  What does it mean for patient care at a time when genetic counseling services are more needed than ever?  


Many hospitals are struggling to recruit and retain genetic counselors for their practices and are looking for alternatives when there aren’t independent genetic counseling services locally available.  One option many medical practices are relying on is genetic counseling services provided by the testing laboratories.  


While lab-based genetic counseling services are filling an important need, there is a conflict of interest inherent in this arrangement.   Genetic counselors’ primary objective has historically been to help patients navigate difficult medical genetic information and decisions, supporting their autonomy.  But as laboratory employees, genetic counselors must also consider their employer’s interests, which includes increasing the uptake of genetic testing.


Challenges regarding conflict of interest in research and healthcare are not new, however this is an area of increasing concern in genetics.   


For more on this topic check out our commentary recently published in Genetics and Medicine and read our recent post, published on Harvard Law Bill of Health blog, written with our colleagues Marsha Michie and Megan Allyse.


An important part of our mission at Genetic Support Foundation is to address issues related to conflict of interest and to provide options for independently developed educational resources for patients and providers and genetic counseling services that are free from the commercial bias.  

Why you should support GSF

As the end of the year draws near, I have been thinking a lot about what GSF means to me, and why I think you should consider making a gift to GSF this year.

It has been an amazing opportunity to work with GSF as a genetic counselor.  To be able to walk with people during incredibly important and often very difficult times in life.  To try to help people make meaning of the uncertain or unimaginable when it comes to their health or that of a loved one.  To offer support and understanding and hope.   Whether it is through our work in supporting an expectant couple through the grief of the diagnosis of a life limiting condition in their unborn baby; or helping a cancer patient and their adult child recognize the tremendous power of genetic information for prevention of future cancers in a family with a strong inherited susceptibility.  This work is profoundly important and I believe it is critical that our profession keep focus on our patients first, and not be compromised  by commercial interests.

Posted in News on Nov 29th, 2016

Chromosomal Microarray (CMA)

Chromosomal microarray (CMA) is a technology that the American College of Obstetricians and Gynecologists now recommends be offered as a first-tier test for any woman undergoing diagnostic testing to replace the standard karyotype that has been used in practice for prenatal diagnosis for decades. This is a big change in practice; while the result may be an increase in the number of genetic differences that can be diagnosed through prenatal testing, it also comes with more uncertainty for expectant parents and healthcare providers who are trying to make sense of the results that may come from this testing.


First let me give some background on why the CMA test is different than the karyotype using the analogy of a library.  The nucleus of each of our cells contains our genetic information.  Imagine the nucleus to be like the library of the cell.  Each of us have about 20,000 pairs of genes, and each of these genes could be considered to be like an individual instruction book that tells the body how to build a specific protein that will have a specific job in our body.  The proteins that are built from our genes do everything that our bodies need to grown and function.  Our genes, (aka instruction books) are organized on chromosomes.  In this analogy, consider each chromosome to be like a large bookcase.  


The karyotype is a picture of the chromosomes and basically allows us to look at and count these bookcases.  In doing this we can see if there are any extra or missing bookcases (chromosomes).  Typically humans have 23 chromosomes inherited from their mother and 23 from their father in matched pairs, so 46 all together.  An extra or missing chromosome causes specific genetic conditions.  For instance, a baby with Down syndrome has inherited an extra copy of the 21st chromosome.    


The karyotype can also allow us to see if there are big structural changes in the chromosomes.  You could imagine this to be a scenario in which a few book shelves had been completely removed from the bookcase (so now a 10 shelf bookcase is a 7 shelf bookcase, for example).  This type of big change can be seen in looking at a picture of the chromosomes.  


The chromosomal microarray (CMA) test is different in that it allows us to see smaller genetic changes than can be seen by looking at the karyotype.  These changes are often referred to as Copy Number Variants, or CNVs.  A CNV is a segment of genomic information that has been duplicated or deleted.  So think of this as the equivalent of a few books on a shelf that have been removed (a deletion) or there are multiple copies of the same few books on the shelf (a duplication).  


Sometimes CNVs are known to cause genetic conditions resulting in health and developmental concerns.  Sometimes we are unsure what will result with certain CNVs.  Other times we see CNVs that appear to be completely normal variations, in which case we do not think they will cause any health or developmental concerns.  


With the karyotype, we usually have a pretty good idea of generally what to expect when we find  an extra or missing chromosome, or when there is a large change in the structure of a chromosome.  


But with CNVs, the meaning of the results is often much less clear.  Sometimes a CNV will be reported as being of “uncertain significance” which means that we just don’t know enough about it yet to determine if it is likely to cause health and/or developmental concerns or not.  Sometimes we find a CNV that we think will cause a health problem, but exactly what that will be or how severe it will be is unknown.  Sometimes when there is uncertainty, it will be recommended to test the parents to see if ether of them also have the same CNV.  This may provide some reassurance if a parent has the same CNV and they are in good health.  But we know there can be differences in how these variants are expressed from parent to child.  Furthermore, there can be situations in which a parent learns they also have the variant identified in the baby or their child, and rather than providing reassurance it leads to more questions.  Is there something wrong with me?  Did I pass on something harmful to my baby?  


Formerly, the American College of Obstetricians and Gynecologists recommended chromosomal microarray be considered  as a prenatal testing option in instances where there were abnormalities seen on ultrasound.  This is because in about 6% of those cases, CMA would provide an explanation that karyotype could not.  In other words, there would be a CNV (a few extra or missing books on a shelf) that karyotype could not see that could provide an explanation for the ultrasound findings.  


Research has found that in cases where ultrasound and karyotype are normal, a significant CNV that is believed to be likely associated with some health or developmental effect will be seen in 1.7% of cases.  Considering this, ACOG now recommends that CMA be made available to ALL women considering diagnostic testing such as amniocentesis.  


This means that more babies will be diagnosed with genetic conditions that would not have been identified from the traditional karyotype test.  It also means that many more families will be receiving information about their babies that may be unclear.  As genetic tests become increasingly complex, it is of utmost importance that women and couples receive pretest genetic counseling so that they can really understand all of the potential benefits, drawbacks, and uncertainties inherent with these tests.  

New Practice Guidelines for Prenatal Genetic Testing

Important guidelines in the area of prenatal genetics were recently published in the journal, Obstetrics and Gynecology (aka “The Green Journal”).  The American College of Obstetricians and Gynecologists (ACOG) and the Society of Maternal-Fetal Medicine (SMFM) collaborated on two new important references:  Practice Bulletin #162 Prenatal Diagnostic Testing for Genetic Disorders, and Practice Bulletin #163 Screening for Fetal Aneuploidy.  These are the first updated guidelines on these topics in nearly a decade and each offers a thorough assessment on currently available prenatal testing technologies as well important points to consider for any provider who provides prenatal care.  They are companion pieces and we encourage you to read them in their entirety when you have an opportunity. Below we summarize the highlights.  
Practice Bulletin number 162:  Prenatal Diagnostic Testing for Genetic Disorders

In 2007 ACOG shook things up by stating that all women (not just those deemed to have a higher chance to have a baby with a genetic condition) should have the option to undergo prenatal diagnostic genetic testing.  This recommendation did not change with the updated guidelines.  ACOG/SMFM still contend that all women should have the option of prenatal testing, including diagnostic tests such as amniocentesis and chorionic villus sampling (CVS). What has changed are the number of prenatal testing options.  With a growing number of testing choices, the decisions faced by expectant patients and couples are more complex than ever before. From the guideline:  


It is important that patients understand the benefits and limitations of all prenatal screening and diagnostic testing, including the conditions for which tests are available and the conditions that will not be detected by testing.”  


This is a great expectation!  Certainly even providers who think about these tests day in and day out struggle in deciphering the different benefits and limitations of each of these tests, as well as the variable conditions that each test may detect!  While it is perhaps a lofty goal, Genetic Support Foundation agrees wholeheartedly with the importance of this statement above. It is essential that individuals be provided enough information and context to make informed decisions when it comes to prenatal genetic testing.

Key updates with guideline #162:

  • Chromosomal microarray analysis should be the primary offered diagnostic method when ultrasound indicates structural abnormalities in the fetus.  Microarray should be made available to any patient choosing to undergo invasive diagnostic testing.  
  • New research indicates that the risk for miscarriage associated with amniocentesis and chorionic villus sampling may be lower than previously reported.  In the hands of experienced providers, the guideline suggests a miscarriage risk of 0.1% – 0.3%.  

Practice Bulletin number 163:  Screening for Fetal Aneuploidy

This document provides an excellent overview and nice comparison table of the various prenatal screening tests available for the assessment of chromosome conditions in the fetus. Technologies reviewed in detail include serum screening such as the triple and quad screening, combined screening such as first trimester screening, integrated screening and sequential screening and the more recently available cell-free DNA screening. The most important take away is that choices about prenatal screening options are complex.  


No one screening test is superior to other screening tests in all test characteristics. Each test has relative advantages and disadvantages. Screening for aneuploidy should be an informed patient choice, with an underlying foundation of shared decision making that fits the patient’s clinical circumstances, values, interests, and goals.”  


Key points with guideline #163:

  • Women who have any negative screening test should not be offered subsequent screening tests. Parallel testing with multiple screening tests should not be done.
  • Cell-free DNA screening is not a replacement for diagnostic testing.  
  • Any woman with a positive screening test including traditional serum screening or cell-free DNA screening results should be offered follow-up genetic counseling and the option to undergo diagnostic testing.
  • Women who undergo preimplantation genetic diagnosis should be offered aneuploidy screening and diagnostic testing.
  • Cell-free DNA screening for microdeletions is not recommended.  
  • Cell-free DNA screening is not recommended for multiple pregnancies.  

In the future, we will explore some points raised in these two guidelines in more detail including, the potential for toxic knowledge with chromosomal microarray testing and why genetic counseling in these situations. We will also explore the potential issues with predicting a lower risk of miscarriage associated with diagnostic testing at a time when some studies suggest that the risk may actually increase as fewer women undergo these tests and providers become less practiced in performing the procedures.  

One point that we strongly agree with is this:  

“Screening for aneuploidy should be an informed patient choice, with an underlying foundation of shared decision making that fits the patient’s clinical circumstances, values, interests, and goals.”  

Whether you are are patient, a healthcare professional, or policy maker, we at the Genetic Support Foundation hope that you will find information here on our website that will help support this goal.