Case #1 - Negative Results

Hey there!

This week I talk about a case I had observed during my training that has stuck with me through the years for one particular reason. This is also the first of many cases that I want to write about, so stay tuned!

Background:

A non-consanguineously married couple (i.e., individuals who are not closely related to each other outside of marriage), came with a history of two pregnancy losses. In their first pregnancy, the fetus was identified to have hydrocephalus, an abnormal buildup of cerebrospinal fluid in the brain, which could be attributed to the chicken pox infection during the pregnancy. In the second pregnancy, the fetus was had a lethal form of skeletal dysplasia, which is an abnormal development of a baby's bones, joints, and cartilage. They came to the clinic at about 12 weeks into their third pregnancy, worried about the recurrence risk and to understand the chances of a healthy pregnancy.

Now, along with giving them the rundown about what are genes, chromosomes, genetic v/s hereditary, and all of that, they were also advised to undergo a few tests.

The first test was a karyotype for both partners. A karyotype is essentially a picture of the chromosomes that is used to determine the chromosomal number and structure. A structural problem in the chromosomes is one of the common causes of pregnancy losses. The karyotype results were normal for both partners.

Along with the karyotype, a whole exome sequencing was suggested to check if the couple were carriers for genes related to bone deformity, or skeletal dysplasia. We have thousands of genes that are identical and present in all our cells. These genes give instructions for normal body functioning. Think of it like a manual for how to make the human body and its functioning. If there is a typo, or a change in any of the genes, the instructions are not read correctly, leading to an error in the body. A whole exome sequencing test was suggested to read all the genes and check for typos that may have happened in any of the genes that give instructions for skeletal development. This test was performed for both partners to check if the skeletal dysplasia identified in the second pregnancy was inherited or de novo, i.e., had happened in that pregnancy as an isolated event and not been passed on by the couple.

Ideally, in cases where there is a fetal anomaly, the best option to get maximum clarity is to perform genetic testing on the fetus itself. However, this usually does not happen because of lack of information or awareness. A lot of times, the families are also not in the emotional headspace to understand the importance of testing. In such cases, the next best option is to test the couple to confirm if the anomaly is genetic and to differentiate between inherited v/s de novo genetic disorders.

This test was also uninformative as the couple were not identified to have any changes in genes related to skeletal dysplasia, or any other genes.

So, a hereditary issue was ruled out, with the exception of a small possibility of germline mosaicism. Germline mosaicism is a situation where the changes in the genes are limited to the germ cells, or sperm and egg, only. These changes are usually not picked up on regular genetic testing because they are present in a very small population of cells that are not being tested.

Anyway, the point I’m trying to make is that both tests were uninformative. So now what? And why am I telling you about this couple?

The couple were called for a post test counseling session where the test results were explained. In the absence of a confirmed genetic cause, the couple did not get the answers that they were looking for. And here’s why I am writing about this case -

While we were discussing the options of follow up scans and closely monitoring the fetal growth parameters, the lady brought up the option to terminate the pregnancy because of her fears of losing the current pregnancy as well. This is where we need genetic counselors.

As an observer to this case, I could sense that she was going through a lot of emotions including -

Fear and anxiety about the possibility of another pregnancy loss or having a child with severe health issues. This fear was compounded by the previous two losses and the unknowns associated with the current pregnancy.

Grief and sadness about already having endured the heartbreak of losing two pregnancies, which is a significant emotional burden. The thought of facing another loss had amplified her grief.

Confusion and uncertainty due to lack of a confirmed diagnosis.

Stress and overwhelm on managing the emotional, physical, and medical aspects of recurrent pregnancy losses, especially when facing the complexities of genetic testing and counseling.

A genetic counselor is well-suited to address these emotions for several reasons:

Specialized Knowledge: Genetic counselors have extensive training in genetics, genetic testing, and hereditary conditions. They can provide clear, accurate information to help the couple understand their situation and the implications of their test results.

Emotional Support: Genetic counselors are trained to offer empathetic support, helping individuals process complex emotions and providing a safe space to discuss their fears and concerns.

Decision-Making Assistance: They can guide the couple through their options, helping them make informed decisions about their pregnancy based on the available information and their personal values and preferences.

Resource Provision: Genetic counselors can connect the couple with additional resources, such as support groups, mental health professionals, and specialists in maternal-fetal medicine, to provide comprehensive care.

Risk Assessment: They can help assess the risk of recurrence and explain the probabilities in a way that is understandable, which can help the couple manage their expectations and plan for the future.

Continued Care: Genetic counselors often provide ongoing support throughout the pregnancy and beyond, ensuring that the couple receives the help they need at different stages of their journey.

It’s been over 3 years and I still remember this session. It illustrates the profound impact that recurrent pregnancy losses and uncertain genetic test results can have on a couple's emotional and psychological well-being. By addressing both the informational and emotional needs of the couple, we, as genetic counselors, play a crucial role in helping couples, families and individuals navigate the challenges of recurrent pregnancy losses and the uncertainties of genetic testing.

That’s my first case for this series and I hope you liked it!

Is there anything you would have done differently? Let me know!

Best,

Simran.