Ethical Issues in Presymptomatic Genetic Testing for Minors: A dilemma in Li-Fraumeni Syndrome
- First Online:
In 2001, a French expert panel recommended that presymptomatic tests should not be carried out on minors in families affected by Li-Fraumeni syndrome (LFS), flying in the face of possible parental demands for such testing. We decided to investigate the legitimacy of such a recommendation. We conducted a national multicenter survey using self-administered questionnaires mailed to French oncogeneticists in 33 regional centers in France. We aimed to (1) determine the extent to which these doctors were confronted with parental requests for TP53 testing, (2) study how they responded to these requests and the arguments used and (3) assess the attitude of oncogeneticists concerning the normative framework regulating the prescription of tests for minors. Twenty oncogeneticists stated that they had managed at least one LFS family. Eleven of these doctors had been confronted with parental requests for testing and three had prescribed such tests on at least one occasion. The oncogeneticists gave balanced medical, psychological and ethical arguments, highlighting the dilemma they face in the decision-making process. This dilemma is due to the lack of a consensus concerning this recommendation, which aims to protect the minor by limiting presymptomatic tests to cases in which a clear medical benefit can be demonstrated but which prevents the unique situation of particular families from being taken into account. In conclusion, the recommendation has a normative status but first, from a clinical stance, it is difficult to dissociate it from the evaluation of individual family situations, and second, the benefit of a specific medical follow-up for TP53 mutation carriers is currently being investigated.
KeywordsLi-Fraumeni Syndrome Predictive genetic testing Medical ethics Minors
- American-Society-of-Human-Genetics. (1995). Points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents. American Society of Human Genetics Board of Directors, American College of Medical Genetics Board of Directors. American Journal of Human Genetics, 57(5), 1233–1241.Google Scholar
- Beauchamp, T., & Childress, J. (2008). Principles of biomedical ethics, 6th edition.Google Scholar
- Codori, A. M., Zawacki, K. L., Petersen, G. M., Miglioretti, D. L., Bacon, J. A., Trimbath, J. D., et al. (2003). Genetic testing for hereditary colorectal cancer in children: long-term psychological effects. American Journal of Medical Genetics. Part A, 116A(2), 117–128.PubMedCrossRefGoogle Scholar
- European-Society-of-Human-genetics (2008). Genetic testing in asymptomatic minors. https://www.eshg.org/eshgdocs.0.html. Accessed 4 February 2011.
- Lammens, C.R., Aaronson, N.K., Wagner, A., Sijmons, R.H., Ausems, M.G., Vriends, A.H., et al. (2010). Genetic testing in Li-Fraumeni syndrome: uptake and psychosocial consequences. Journal of Clinical Oncology Google Scholar
- Masciari, S., Van den Abbeele, A. D., Diller, L. R., Rastarhuyeva, I., Yap, J., Schneider, K., et al. (2008). F18-fluorodeoxyglucose-positron emission tomography/computed tomography screening in Li-Fraumeni syndrome. JAMA: The Journal of the American Medical Association, 299(11), 1315–1319.CrossRefGoogle Scholar
- National-Comprehensive-Cancer-Network (2010). The NCCN clinical practice guidelines in OncologyT Li-Fraumeni syndrome (Version 1.2010). 2010 National Comprehensive Cancer Network, Inc. http://www.nccn.org/professionals/physician_gls/pdf/genetics_screening.pdf. Accessed 4 Feburary 2011.
- Nichols, K. E., Malkin, D., Garber, J. E., Fraumeni, J. F., Jr., & Li, F. P. (2001). Germ-line p53 mutations predispose to a wide spectrum of early-onset cancers. Cancer Epidemiology, Biomarkers & Prevention, 10(2), 83–87.Google Scholar
- Pelias, M. K. (2006). Genetic testing of children for adult-onset diseases: is testing in the child’s best interests? The Mount Sinai Journal of Medicine, 73(3), 605–608.Google Scholar
- Petitjean, A., Mathe, E., Kato, S., Ishioka, C., Tavtigian, S. V., Hainaut, P., et al. (2007). Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: lessons from recent developments in the IARC TP53 database. Human Mutation, 28(6), 622–629.PubMedCrossRefGoogle Scholar
- Ruijs, M. W., Verhoef, S., Rookus, M. A., Pruntel, R., van der Hout, A. H., Hogervorst, F. B., et al. (2010). TP53 germline mutation testing in 180 families suspected of Li-Fraumeni syndrome: mutation detection rate and relative frequency of cancers in different familial phenotypes. Journal of Medical Genetics, 47(6), 421–428.PubMedCrossRefGoogle Scholar
- Schwarzbraun, T., Obenauf, A. C., Langmann, A., Gruber-Sedlmayr, U., Wagner, K., Speicher, M. R., et al. (2009). Predictive diagnosis of the cancer prone Li-Fraumeni syndrome by accident: new challenges through whole genome array testing. Journal of Medical Genetics, 46(5), 341–344.PubMedCrossRefGoogle Scholar
- The-Children’s-Hospital-of-Philadelphia (2009). Hereditary cancer predisposition program: Li Fraumeni syndrome. 1996–2010 The Children’s Hospital of Philadelphia. http://www.chop.edu/service/hereditary-cancer-predisposition-program/genetic-syndromes-with-cancer-risks/li-fraumeni-syndrome.html. Accessed 4 February 2011.
- Villani, A., Tabori, U., Schiffman, J., Shlien, A., Beyene, J., Druker, H., et al. (2011). Biochemical and imaging surveillance in germline TP53 mutation carriers with Li-Fraumeni syndrome: a prospective observational study. The Lancet Oncology, 12(6), 559–567. doi:10.1016/s1470-2045(11)70119-x.PubMedCrossRefGoogle Scholar
- World-Medical-Association (1998). Declaration of Ottawa on child health. http://www.wma.net/fr/30publications/10policies/c4/. Accessed 11.07.2012.