I GENETIC RISK ASSESSMENT ^311 ^391
Genetic testing is poised to play a greater role in the practice of obstetrics and gynecology. With the success of the Human Genome Project, a growing number of diseases are now known to have a genetic contribution.
In addition to conditions widely understood as having a genetic contribution, such as fragile X syndrome, neural tube defects, and hemoglobinopathies, other conditions commonly seen in gynecologic practice—for example, diabetes mellitus, hypertension, cancer (breast, endometrial, ovarian, and colon), and cancer syndromes (such as hereditary breast and ovarian cancer syndrome and Lynch syndrome)—are also known to have a genetic contribution. Identification and management of genetic risk factors have the potential to affect the quality and length of a woman’s life. Genetic risk factors that may be identified in a particular patient include the relatively common ones associated with cancer and heart disease, as well as more specific ones that may be discovered through the patient’s family or medical history (Box 3-12).The list of medical conditions that have, or are suspected to have, a genetic contribution continues to grow as new genetic risks are discovered, and additional tests for these conditions are continually developed. The National Center for Biotechnology Information of the National Institutes of Health provides a resource for reviewing these conditions and tests (available at www.ncbi.nlm.nih.gov/gtr/). Clinicians need to maintain competence in the face of this evolving science, including the ability to identify patients within their practices who are candidates for genetic counseling, genetic testing, or both.
Genetic risk assessment has an especially important role in preconception and prenatal screening. The testing may affect a patient’s decisions regarding her reproductive choices. Genetic risk assessment not related to reproductive care has the potential for identifying factors that will affect the patient’s health and possible longevity.
The purpose of testing in this case isBox 3-12. Red Flags for Genetic Conditions ^
• Family history of a known or suspected genetic condition
• Ethnic predisposition to certain genetic disorders
• Consanguinity
• Multiple affected family members with the same or related disorders
• Earlier than expected age of onset of disease
• Diagnosis in less-often-affected sex
• Multifocal or bilateral occurrence of disease (often cancer) in paired organs
• Disease in the absence of risk factors or after application of preventive measures
• One or more major malformations
• Developmental delays or mental retardation
• Abnormalities in growth (growth restriction, asymmetric growth, or excessive growth)
• Recurrent pregnancy losses (two or more)
Data from National Coalition for Health Professional Education in Genetics. Genetic red flags. Available at: http://www.nchpeg.org/index.php?option=com_content&view=arti cle&id=59&Itemid=75. Retrieved on September 26, 2013.
to identify risks that may be modified by changes in lifestyle or therapeutic interventions (see also the “Cancer Screening and Prevention” section later in Part 3 and the “Cancer Diagnosis and Management” section in Part 4).
Family History
A family history that may identify genetic risks should be gathered. Women should be informed of genetic risks and offered appropriate counseling and testing. Specific counseling is needed for testing that may have medical or psychosocial consequences. Counseling includes outlining the risks, benefits, and alternatives to genetic testing and should be neutral. Pretest and posttest counseling facilitate women’s access to appropriate health care. Most obstetrician-gynecologists are capable of basic genetic risk identification and counseling, but referral may be needed for comprehensive counseling. Personnel with more advanced training, such as genetic counselors and medical geneticists, are appropriate for patients with common and more unusual abnormalities.
Assisted Reproductive Technology
Genetic services also may play a role in assisted reproductive technology. Gamete donors should be screened for heritable disorders through evaluation of pedigree, counseling, and—when appropriate—testing procedures. In some circumstances it is possible to identify embryos affected by certain diseases before implantation, in which case the affected embryos are not transferred. Preimplantation genetic testing often is used in instances when the potential disease might have a significant effect on the health of the future child. Consideration of such screening can raise ethical issues that the health care provider, genetic counselor, and patient should openly discuss before implementation.
Ethical Issues
Ethical issues related to the use of information gathered as a result of all genetic risk assessments need to be anticipated and discussed with the patient at the first genetic counseling session. Concerns about the effect of information about genetic conditions on such factors as employability and insurability have been raised. The Genetic Information Nondiscrimination Act of 2008 is designed to prohibit discrimination in health insurance coverage and employment based on genetic information. Patients should be encouraged to consider the importance of relatives being made aware of genetic disorders in the family, and confidentiality issues must be considered carefully (see also the “Human Resources” section in Part 1). The patient should be informed prospectively about policies regarding the use of information and legal requirements. Ordinarily, information may not be revealed without the patient’s express consent. However, there may be situations in which the information may not be protected. The health care provider should be familiar with state or federal requirements regarding genetic screening, reporting, disclosure, breach of confidentiality, and discrimination based on genetic information.
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