Chapter 064. The Practice of Genetics in Clinical Medicine (Part 6) pot

Chapter 064. The Practice of Genetics
in Clinical Medicine
(Part 6)

Follow-Up Care after Testing
Depending on the nature of the genetic disorder, posttest interventions may
include (1) cautious surveillance and appropriate health care screening, (2)
specific medical interventions, (3) chemoprevention, (4) risk avoidance, and (5)
referral to support services. For example, patients with known pathologic
mutations in BRCA1 or BRCA2 are offered intensive screening as well as the
option of prophylactic mastectomy and oophorectomy. In addition, such women
may be eligible for preventive treatment with tamoxifen, or enrollment in a
chemoprevention clinical trial. In contrast, those at known risk for Huntington's
disease are offered continued follow-up and supportive services, including
physical and occupational therapy, and social services or support groups, as
indicated. Specific interventions will change as translational research continues to
enhance our understanding of these genetic diseases and as more is learned about
the functions of the gene products involved.
Individuals who test negative for a mutation in a disease-associated gene
identified in an affected family member must be reminded that they may still be at
risk for the disease. This is of particular importance for common diseases such as
diabetes mellitus, cancer, and coronary artery disease. For example, a woman who
finds that she does not carry the disease-associated mutation in BRCA2 previously
discovered in her family must be reminded that she still requires the same breast
cancer screening recommended for the general population.[newpage]
Genetic Counseling and Education
Genetic counseling should be distinguished from genetic testing and
screening, even though genetic counselors are often involved in issues related to
testing. Genetic counseling refers to a communication process that deals with
human problems associated with the occurrence or risk of a genetic disorder in a
family. Genetic risk assessment is complex and often involves elements of

uncertainty. Counseling therefore includes genetic education as well as
psychosocial counseling. Genetic counselors may be called upon by other health
care professionals (or by individual patients and families) to address a broad range
of issues directly and indirectly related to genetic disease (Table 64-1). The role of
the genetic counselor includes the following:
Gather and document a detailed family history;
Educate patients about general genetic principles related to disease
risk, both for themselves and for others in their family;
Assess and enhance the patient's ability to cope with the genetic
information offered;
Discuss how nongenetic factors may relate to the ultimate expression
of disease;
Address medical management issues;
Assist in determining the role of genetic testing for the individual and
family;
Ensure that the patient is aware of the indications, process, risks,
benefits, and limitations of the various genetic testing options;
Assist the patient, family, and referring physician in the interpretation
of the test results; and
Refer the patient and other at-risk family members for additional
medical and support services, if necessary.
Table 64-1 Indications for Genetic Counseling
Advanced maternal (>35) or paternal (>50) age
Consanguinity
Previous history of a child with birth defects or a genetic disorder
Personal or family history suggestive of a genetic disorder
High-risk ethnic groups; known carriers of genetic alterations
Documented genetic alteration in a family member
Ultrasound or prenatal testing suggesting a genetic disorder
The complexity of genetic counseling and the broad scope of genetic

diseases have led to the development of specialized, multidisciplinary clinics
designed to provide broad-based support and medical care for those at risk and
their family members. Such specialty clinics are well established in the areas of
cancer and neurodegenerative disorders. The multidisciplinary teams are often
composed of medical geneticists, specialist physicians, genetic counselors, nurses,
psychologists, social workers, and biomedical ethicists who work together to
consider difficult diagnostic, treatment, and testing decisions. Such a format also
provides primary care physicians with invaluable support and assistance as they
follow and treat at-risk patients.
The approach to genetic counseling has important ethical, social, and
financial implications. Philosophies related to genetic counseling vary widely by
country and center. In North American centers, for example, counseling is
generally offered in a nondirective manner, wherein patients learn to understand
how their values factor into a particular medical decision. Nondirective counseling
is particularly appropriate when there are no data demonstrating a clear benefit
associated with a particular intervention or when an intervention is considered
experimental. For example, nondirective genetic counseling is employed when a
person is deciding whether to undergo genetic testing for Huntington's disease
(Chap. 365). At this time, there is no clear benefit (in terms of medical outcome)
to an at-risk individual undergoing genetic testing for this disease, as its course
cannot be altered by therapeutic interventions. However, testing can have an
important impact on this individual's perception of the future and his or her
interpersonal relationships and plans for reproduction. Therefore, the decision to
pursue testing rests on the individual's belief system and values. On the other
hand, a more directive approach is appropriate when a condition can be treated. In
a family with FAP, colon cancer screening and prophylactic colectomy should be
recommended for known APC mutation carriers. The counselor and clinician
following this family must ensure that the at-risk family members have access to
the resources necessary to adhere to these recommendations.
Genetic education is central to an individual's ability to make an informed

decision regarding testing options and treatment. Although genetic counselors
represent one source of genetic education, other health care providers also need to
contribute to patient education. Patients at risk for genetic disease should
understand fundamental medical genetic principles and terminology relevant to
their situation. This includes the concept of genes, how they are transmitted, and
how they confer hereditary disease risk. An adequate knowledge of patterns of
inheritance will allow patients to understand the probability of disease risk for
themselves and other family members. It is also important to impart the concepts
of disease penetrance and expression. For most complex adult-onset genetic
disorders, asymptomatic patients should be advised that a positive test result does
not always translate into future disease development. In addition, the role of
nongenetic factors, such as environmental exposures, must be discussed in the
context of multifactorial disease risk and disease prevention. Finally, patients
should understand the natural history of the disease as well as the potential options
for intervention, including screening, prevention, and—in certain circumstances—
pharmacologic treatment or prophylactic surgery.