The Power of Incidental Findings

Imagine that you are a geneticist that receives a patient in your clinic with a rare genetic disorder. Your patient is a 3 year old girl with severe learning dificulties. After looking at her sample under the microscope you find nothing of note and so you dismiss the case as inconclusive. Up until recently, that was the normal scenario for most cases in the genetics clinic. Today however, with next generation sequencing techniques, we are able to look at base pair level resolution, about 10,000 times the resolution microscopy can afford. At a later date, the resources become available to you and decide to carry out a next generation sequencing analysis for the patient and both parents.

With the results in hand, you identify a candidate mutation most likely to have caused the observed symptoms. You look then at the parents’ genotype to see whether the mutation is inherited and find that the father is not the real biological one, i.e. you are faced with an incidental finding of non-paternity. This is one example of pieces of information contained in the genetic material, not related to the diagnosis, but necessary to carry out the analysis. Incidental findings like these have the potential of dramatically affecting the lives of patients and their families.

How should we deal with incidental findings capable of dramatically affecting families? The answer is not simple. For instance, when non-paternity is identified, the case could be dismissed as non-analyzable to avoid the complex ethical ramifications of such a revelation on the family.

Let’s consider another incidental finding, such as detecting that one of the parents is a carrier of the disease that is causing the mutation in the patient. Such a finding may imply that future children from the couple may also inherit the mutation. Should parents be informed or should they be allowed to choose whether they find out or not?

There are many other incidental findings where strong arguments can be made either for or against informing the family. One example is the discovery of a malignant variant for the APOE gene in the patient, implicated in early onset Alzheimer’s. This is something for which the patient was not tested, but still it has the potential of having a life changing effect on the patients or their parents. Another example is the finding of a malignant mutation for BRCA2, which increases by 70% the chances of developing breast cancer in female carriers. There are many other incidental findings such as these where practitioners are undecided on how to manage that information sensibly.

What it is clear though is that incidental findings will have to be dealt with on an individual basis. Informing the family will depend on the possible effects of the information found as well as personal circumstances. Here I have just limited my exposition to a few common examples of current challenges, but as technology progresses and more patients and families are sequenced, many new conundrums are likely to appear, requiring new ethical debate.

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