Genomic Gray Zones

One of the largest issues in the genomics world is the gray area that accompanies it, especially when dealing with diagnosis. There are a myriad of scientific and technical errors in genetic testing. One is incomplete genetic knowledge. As genetic research is only recently developing, the functions of every present gene in the body are only partially understood, leaving room for misinterpretation. Another drawback is the limited predictive value of a disease, where the identification presence of a gene or mutation in the body does not certify a treatment for the disease. The most important factor however, is the variants of uncertain significance. This refers to the ambiguity when it comes to testing. Unlike normal medical procedures, where a blood test can tell you where you are deficient, genetic testing does not. It often involves an amalgamation of different methods, analogous to fitting puzzle pieces to form a picture. Sometimes, these puzzle pieces don't fit together as nicely as we’d like, containing large bumps, ridges and rough areas. In the realm of genomics, these are uncertainties. Uncertainties come in many shapes and sizes for genetic testing. These refer to whether or not a gene is pathogenic or benign. If the result is inconclusive, this may mean that the mutation is rare/newly discovered, or a known gene impacts different populations differently or there is just a lack of research in this area. Either way, there is no way to treat the outcome of the mutation. In the context of patients, uncertainty leads to anxiety - it is hard to discern the cause of an issue and hence treat it. It also complicates clinical decisions, treatments and preventive measures that cannot be executed with complete certainty. 

 

Today’s patient story follows that of Kanamo. The moniker Kanamo, originating from one of the great himalayan peaks, was chosen as it is symbolic of a strong, resilient and grounded structure that is kind to its visitors, similar to the interviewee. 

 

Kanamo is a kind nurturing figure, who like the bulk of society, dreams of having her own children following her marriage, a natural succeeding step. These dreams, however, were brought down during an anomaly scan that happened in the midst of her pregnancy, where the developing fetus showed a multitude of abnormalities, including multicystic kidneys, deformed vertebra, a hole in the septum (wall between heart chambers) and an incorrectly curved aortic arch (to the right instead of the left). This was topped off with an absence of amniotic fluid in the womb, causing Kanamo and her husband to make the heartbreaking decision to terminate. 

 

‘This was the most difficult part of this whole journey. I remember taking several scans, hoping that each one would show a different outcome, but it never did.’ 

 

The combination and expression of these symptoms indicated clear syndromic or genetic nature As a result, she was referred to the clinic. Here, she was advised to undergo two tests – the QF PCR, which tests common chromosome irregularities, and exome sequencing, which inspects the coding regions of the genes. Both of these however, turned out normal, and hence no clear cause was determined, even though the manifestations said otherwise. The clinic made the executive decision to allow Kanamo to take up a 2nd pregnancy, under the guise that this was an anomaly in the system,but there may still be a chance that this could occur again. When asking Kanamo about this uncertainty, she had this to say:

 

‘Obviously as it is uncertain, there is still a chance of success, so I will take this in a positive way. The manner in which I view this issue is up to me, and I choose positivity.’

 

This is a classical example of the limitations of medical discovery. As genomics is an incredibly vast area of study, it is difficult to understand every gene completely. In this way, an inconclusive result does not necessarily mean that an issue is completely resolved, nor does it mean that it isn't. It begs the question in the patient's mind that if all the tests are normal, why did this issue occur?, and if it happened once, what's stopping it from happening again. The best way to deal with this, is to follow Kamano’s example: take uncertainty as just that; uncertainty - incomplete information that cannot form the basis of a decision.