VI. PEDIATRIC GENETIC TESTING

DNA-based clinical testing is available for over 900 genetic diseases, and research-based testing is offered for hundreds of others. Such testing can aid in making diagnoses, assessing recurrence risks, and providing accurate prognoses. Often genetic testing is initiated prior to the onset of symptoms. This type of testing is known as pre-symptomatic or predictive genetic testing, and is typically offered for adult-onset diseases such as Huntington's chorea or certain types of cancer. Huntington's chorea, or Huntington's disease, is a progressive, fatal, neurological condition that affects movements and memory. Individuals who carry the gene for Huntington's disease usually begin showing symptoms around age 40, though this can vary dramatically between individuals and families. The types of cancer that can be associated with inherited DNA mutations include breast cancer, ovarian cancer, and certain types of colon cancer.

Though DNA-based clinical testing has become a part of routine management for numerous diseases, it presents a unique set of circumstances that separate it from other types of testing. Since a number of genetic mutations are inherited from parents, testing either children or parents will often reveal increased risk for other family members. In the cases of autosomal dominant conditions such as Huntington's disease or Hereditary Breast and Ovarian Cancer syndrome, an affected parent has a 50 percent chance of passing on the defective gene to his or her child.

There are a number of ethical issues associated with the use of pre-symptomatic testing for adult-onset disorders. One important area of discussion focuses on whether genetic testing for these diseases should be initiated in children. Several professional organizations, including the American Academy of Pediatrics and the American Society for Human Genetics, have formal positions stating that children under the age of eighteen years should not undergo genetic testing for adult-onset disorders. The American Society for Human Genetics states: "if medical or psychological benefits of a genetic test will not accrue until adulthood, as in the case of … adult-onset diseases, genetic testing generally should be deferred" (American College of Medical Genetics, pp. 1233–1241), and the World Federation of Neurology Research Group on Huntington's Chorea explicitly recommends not testing any minors.

These policies are driven by the argument that since these are adult-onset disorders for which there is no treatment or medical intervention during childhood, there is no medical benefit to testing. Additionally, children are unable to understand the complexities involved in the testing and therefore cannot provide informed consent. Testing these children, then, potentially could be seen as harmful, as it takes away their right not to know their genetic status.

Proponents of genetic testing in children argue that there are situations when the benefits of testing, either medical or emotional, outweigh the potential harms. This article will explore these arguments in detail, and present a proposal for appropriate use for predictive tests in children.

Pre-symptomatic genetic testing for adult-onset disorders typically involves a detailed informed consent process. This process can include discussions of the natural course of the disease, prognosis, risks to other family members, and treatment options. Some informed consent processes, such as the one outlined by the Huntington's Disease Society of America, require a psychiatric assessment to determine how test results will be viewed, and what potential reactions might occur. This process can be lengthy and challenging for an adult, and would not be possible for a child. The question, then, is raised as to whether parents can consent for the pre-symptomatic genetic testing for children.

Medical decision making for adults is largely guided by respect for persons and autonomy, whereas in pediatrics it is guided by beneficence. With regards to adult medicine, medical decisions made by competent adults who have undergone an appropriate informed consent process are typically respected. In a pediatric setting, the parents traditionally have had the responsibility of medical decision making, where a competent adult is challenged to make decisions not for his or her own care, but for the child's. This is based on the assumptions that parents are typically interested in maintaining their children's best interests and safety; parents are in a position to know what those best interests are by virtue of knowing their children better than anyone else; parents usually must deal with the financial, emotional, and practical aspects of such decisions; and Western society typically has strived to maintain privacy and parental control within a family unit whenever possible. In other words, the autonomy of parents traditionally is respected as long as it supports the benefit of the child; the challenge then becomes balancing the rights of the children with the rights of parents.

Can Predictive Genetic Testing be Harmful?

There are some situations where the desires of the parent, regardless of how well meaning, may not be in the best interest of the child. In the case of pre-symptomatic genetic testing, a parent often has a need to know what the genetic status of a child is, but that information may or may not be beneficial to the child, and even could be harmful. The purpose of an informed consent process for pre-symptomatic testing is to enable individuals to make decisions about whether they want this information, and to consider how it might affect how they live their lives. A child who has undergone genetic testing will never have the option not to know the results of that information. A positive test result in a child may result in potentially serious psychosocial affects on relationships, family, school performance, and self-concept. This is particularly true if the child has watched a great deal of suffering on the part of the parent. A negative test result can lead to survivor guilt or feelings of being ostracized from affected family members. Many adults choose not to undergo testing due to the psychological burden of incorporating a test result into their lives and futures, and opponents of predictive genetic testing in children feel that children should be offered that same freedom from knowledge.

Personal experience can also interfere with a child's ability to understand the complexities of a positive result, or the reassurance of a negative result. For example, a positive DNA test for the genes associated with Breast and Ovarian Cancer syndrome confers a lifetime risk of developing breast or ovarian cancer of approximately 50 to 80 percent, not 100 percent. Conversely, a negative test result for this child reveals that her risk of breast cancer is not zero, but rather that of the general population, which is approximately 10 percent. A child who has watched her mother die from breast cancer may view this positive result as a prediction of her future and a death sentence, instead of indicating an increased risk. This is a heavy burden to place on a child who is already struggling with the loss of a parent.

The nature of genetic material presents an additional challenge to testing individuals of any age, but these issues can be magnified when dealing with children. By definition, genetic testing often reveals information about other family members, and healthcare providers should consider prior to testing how that information will be addressed. Specifically, genetic testing can reveal cases of non-paternity that can have an adverse affect on the relationship between parent and child.

Can Predictive Genetic Testing be Beneficial?

There are potential benefits to pre-symptomatic genetic testing in children. From a parental standpoint, knowing the genetic status can help parents plan financially and emotionally for their child's future. A positive result may mean long-term care issues that can be offset by advanced financial planning. A parent who is afflicted with a genetic disease may seek comfort in knowing that he or she did not pass on the defective gene to a child, even if symptoms of that disease are years away. In the cases of Huntington's disease and certain types of cancer, an affected parent may not survive long enough for their child to reach adulthood, meaning the parent may die not knowing if their child will suffer a similar fate.

The child herself may be comforted by a negative result. There is a strong argument for the emotional benefit of being able to tell a child who is afraid of the disease of a parent that he or she is unlikely to develop the same disease. This is particularly true in an adolescent, who may have been able to identify his or her own risk through research, even if this information was never discussed at home or with a medical practitioner.

In addition, there are potential medical benefits to be considered. In the case of familial adenomatous polyposis (FAP), a familial colon cancer syndrome, colon cancer has been reported in children as young as ten years of age. Approximately 75 percent of those individuals carrying a DNA mutation associated with FAP will develop pre-cancerous polyps before age twenty. In families where this disease has been identified, children of affected parents have a 50 percent chance of having inherited the mutation. For these children, a positive test result would mean a much more rigorous medical course, involving annual colonoscopies to monitor the development of polyps, and most likely a prophylactic colectomy in the future, both measures that could save lives. A negative test result would spare these children from such invasive screening, and reveal their lifetime risk of colon cancer to be that of the general population.

Though it is generally understood that children do not possess the competence to make medical decisions, the situation is less clear for adolescents. Obviously there is no perfect age that competence can be assumed, nor is there a minimum age at which it can be specified as absent. There are adolescents who are capable of engaging in the informed consent process and making medical decisions for themselves. One would hope that, when possible, the decisions of the parent would encompass conversation with the child or adolescent and involve the minor to whatever degree is appropriate for maturity, interest, and responsibility.

The Rule of Earliest Onset

One proposal for determining the appropriate use of predictive tests is the "rule of earliest onset." Simply put, the rule states that "genetic testing should be permitted no earlier than the age of first possible onset of disease" (Kodish, p.391). This guideline allows for the possibility that medical benefit may outweigh potential harms. Employing this basic rule provides several advantages. First, predictive testing is limited to those children for whom there is a potential medical benefit. Though this does not eliminate the possibility that decisions to test will be fueled by additional motivations, it ensures that benefit to the child will be present. Secondly, by delaying testing until an age when symptoms may occur, one maximizes the likelihood that the now older child can participate in the decision-making process. Finally, it is a family-specific guideline for testing that accounts for variation in the age of onset. For example, even though the majority of Huntington's disease occurs in adults, approximately 10 percent of cases are juvenile. In these families, the disease is typically transmitted through a father whose own disease had an earlier than expected presentation. If predictive testing for a child is being considered, and the history reveals that in this particular family the father is the affected individual and his symptoms developed in his twenties, then the rule of earliest onset for this family would suggest testing an adolescent.

Conclusions

Predictive genetic testing in a pediatric setting is complicated by the complexity of the information, the fact that testing decisions are being made by someone other than the person being tested, and the potential impact of the test results. Traditionally it has been thought that predictive genetic testing should not be offered to children under the age of eighteen, and many professional policies have been developed in support of this.

These policies are based on the assumption that "medical or psychological benefits of a genetic test will not accrue until adulthood." This article has discussed situations where there is arguably either a medical or emotional benefit to the child that would warrant testing, and presented a proposal for the use of predictive genetic testing in pediatrics.

rebecca marsick

eric d. kodish

SEE ALSO: Disability; Eugenics; Eugenics and Religious Law; Genetic Counseling, Ethical Issues in; Genetic Counseling, Practice of; Genetic Discrimination; Genetics and Human Self-Understanding; Infanticide; Infants;Pediatrics; and other Genetic Testing and Screening subentries

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INTERNET RESOURCES

American Academy of Pediatrics. 2001. "Ethical Issues with Genetic Testing in Pediatrics (RE9924)." Available from <http://www.aap.org>.

American College of Medical Genetics. 1995. "Points to Consider: Ethical, Legal and Psychological Implications of Genetic Testing in Children and Adolescents," pp. 1233–1241. Available from <http://www.acmg.net>.

American Medical Association. 1995. "Genetic Testing of Children." Available from <http://www.ama-assn.org>.