Clinical Ethics Case Study 8: Should we carry out a predictive genetic test in our young patient?

Abstract

Referral to the Clinical Ethics Committee: A request for genetic testing in childhood. S, a five-year old boy, has recently been seen with his mother C in the paediatric outpatient clinic. Sadly his father N died from metastatic cancer a few months ago, aged 30 years. Other members of N’s family have died in childhood or early adulthood from various forms of cancer. While N was unwell, it was discovered that he carried a mutation in the TP53 gene associated with Li-Fraumeni Syndrome (LFS). LFS is a cancer predisposition syndrome leading to a high risk of various aggressive cancers, including leukaemia, melanoma, soft-issue sarcoma and pancreatic, colon, brain or breast cancer. LFS runs in families and is inherited as an autosomal dominant trait, such that any child of a person with the TP53 gene change will have a 50% risk of inheriting the same mutation and a resultant high chance of developing one of these cancers. The type or age of onset of these cancers cannot be predicted. When N was unwell, his oncologists suggested that S be referred to a clinical genetics service for genetic testing for LFS. At that time the clinical team thought it was appropriate that testing should go ahead, however the laboratory that received the sample for testing let it be known that they thought it was not appropriate to test because S was a minor and that guidelines on genetic testing in children suggested such a test should not be done routinely. Testing therefore did not go ahead. The genetics team then referred S to a consultant paediatrician, recommending annual surveillance in accordance with professional guidelines written by a paediatric oncology society. This surveillance includes a thorough physical examination, routine blood tests (which may reveal leukaemia, for example), abdominal ultrasound to detect intra-abdominal malignancy and other indicated organ-specific surveillance tests. However, none of these measures have been shown to be effective in reducing morbidity or mortality for LFS. When we (the paediatricians) met S and his mother C in the outpatient clinic, we explained the surveillance programme, but indicated that a cancer, if it were to occur, might reveal itself between the annual checks, and might not be detected even if present. We discussed that there is little evidence that surveillance would improve the prognosis even if her son did carry the TP53 gene change. C was also warned that some screening methods, such as CT scanning, produce radiation in high doses and so could actually increase his risk of cancer if he was affected over and above detecting any abnormality. However, MRI scanning would be used when possible. During this recent appointment, C expressed her disappointment that S was not able to receive a genetic test for LFS. She was finding it difficult to manage his at-risk status and was particularly worried that whenever he developed an illness, or abdominal pain (both relatively common in childhood), he would require potentially complex and unpleasant tests. C said that if she knew his gene status, not only would she have greater certainty about what the future held, but unnecessary investigations might be avoided. We established that S was thriving and was not displaying any signs of ill health. We discussed the various issues with C, and although we felt that gene testing was a reasonable option we were concerned that to test now would deny S any say in the matter and that he might (when old enough) decide he would rather not know his risk status. On the other hand, we were also sympathetic to the idea of C’s parental autonomy to make decisions that were best for her family. If S’s status could be established now then he may be able to avoid further screening, although the uncertainty over the benefit of screening is also a difficult issue to resolve. We are approaching the ethics committee with the following questions in mind: 1. Should S be tested now for Li-Fraumeni syndrome? 2. In cases like this, how should we balance the interests of S with those of C or their wider family? 3. If we decide not to test S, how should this be managed in the clinic and with S over time? Or, If we do test him, how should this result be disclosed to S and when? 4. How should intra-disciplinary conflicts, such as a disagreement between the laboratory and the clinical team, be handled in practice?