Chapter 064. The Practice of Genetics in Clinical Medicine (Part 5)

Molecular analysis is generally more informative if testing is initiated in a symptomatic family member, since the identification of a mutation can direct the testing of other at-risk family members (whether they are symptomatic or not). In the absence of additional familial or environmental risk factors, individuals who test negative for the mutation found in the affected family member can be informed that they are at general population risk for that particular disease. Furthermore, they can be reassured that they are not at risk for passing on the mutation to their children. On the other hand, asymptomatic family members...
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Chapter 064. The Practice of Genetics in Clinical Medicine (Part 5) Chapter 064. The Practice of Genetics in Clinical Medicine (Part 5) Molecular analysis is generally more informative if testing is initiated in asymptomatic family member, since the identification of a mutation can direct thetesting of other at-risk family members (whether they are symptomatic or not). Inthe absence of additional familial or environmental risk factors, individuals whotest negative for the mutation found in the affected family member can beinformed that they are at general population risk for that particular disease.Furthermore, they can be reassured that they are not at risk for passing on themutation to their children. On the other hand, asymptomatic family members whotest positive for the known mutation must be informed that they are at increasedrisk for disease development and for transmitting the alteration to their children. Clinicians providing pretest counseling and education should assess thepatients ability to cope with test results. Individuals who demonstrate signs andsymptoms of emotional distress should have their psychosocial needs addressedbefore proceeding with molecular testing. Generally, genetic testing should not beoffered at a time of personal crisis or acute illness within the family. Patients willderive more benefit from test results if they are emotionally able to comprehendand absorb the information. It is important to assess patients preconceived notionsof their personal likelihood of disease in preparing pretest educational strategies.Often, patients harbor unwarranted fear or denial of their likelihood of geneticrisk. Genetic testing has the potential of affecting the way individual familymembers relate to one another, both negatively and positively. As a result, patientsaddressing the option of molecular testing must consider how test results mightimpact their relationships with relatives, partners, spouses, and friends. In familieswith a known genetic mutation, those who test positive must consider the impactof their carrier status on their present and future lifestyles; those who test negativemay manifest survivor guilt. Family members are likely to differ in their emotionaland social responses to the same information. Counseling should also address thepotential consequences of test results on relationships with a spouse or child.Parents who are found to have a disease-associated mutation often expressconsiderable anxiety and despair as they address the issue of risk to their children. When a condition does not manifest until adulthood, clinicians will befaced with the question of whether at-risk children should be offered moleculartesting and, if so, at what age. Although the matter is debated, several professionalorganizations have cautioned that genetic testing for adult-onset disorders shouldnot be offered to children. Many of these conditions are not preventable;consequently, such information can pose significant psychosocial risk to the child.In addition, there is concern that testing during childhood violates a childs right tomake an informed decision regarding testing upon reaching adulthood. On theother hand, testing should be offered in childhood for disorders that may manifestearly in life, especially when management options are available. For example,children at risk for familial adenomatous polyposis (FAP), associated withalterations in the APC gene, may develop polyps as early as their teens, andprogression to an invasive cancer can occur by their twenties. Likewise, childrenat risk for MEN type 2, which is caused by mutations in the RET proto-oncogene,may develop medullary thyroid cancer early in childhood, and the issue ofprophylactic thyroidectomy should be addressed with the parents of children withdocumented mutations (Chap. 345). Informed Consent When the issue of testing is addressed, patients should be stronglyencouraged to involve other relatives in the decision-making process, as moleculardiagnostics will likely have an impact on the entire family. Informed consent formolecular testing begins with detailed education and counseling (Fig. 64-3). Thepatient must fully understand the risks, benefits, and limitations of undergoing theanalysis. Informed consent should include a written document, drafted clearly andconcisely in a language and format that is comprehensible to the patient, whoshould be made aware of the disposition of test results. Informed consent shouldalso include a discussion of the mechanics of testing. Most molecular testing forhereditary disease involves DNA-based analysis of peripheral blood. In themajority of circumstances, test results should be given only to the individual, inp ...