Genetic counselors: Your partners in clinical practice
ABSTRACTAs our understanding of the human genome has grown, so too has the need for health care providers who can help patients and families understand the implications of these new discoveries for their health care. Increasingly, genetic counselors are working in partnership with physicians to provide a continuum of care from risk assessment to diagnosis. In this article, we explain the process of genetic counseling and its value for patients who have a personal or family history of a hereditary condition.
KEY POINTS
- The sequencing of the human genome has provided valuable information about the genetic causes of many conditions, but it has also uncovered tremendous complexities.
- Genetic counselors are master’s-trained allied health care professionals with specific expertise in identifying and educating patients at risk for inherited conditions.
- Genetic testing should not be ordered without informed consent and without appropriate counseling before and after the test.
- Huntington disease, which is inherited in an autosomal dominant manner, illustrates the need for genetic counseling before predictive testing.
- The National Society of Genetic Counselors (www.nsgc.org) and the American Board of Genetic Counseling (www.abgc.net) provide searchable databases of genetic counselors.
EXPLAINING POSITIVE GENETIC TESTING RESULTS
If genetic testing identifies a mutation, genetic counselors can help patients understand the implications of the results for themselves and for their relatives. Some patients become quite inquisitive, and the genetic counseling session morphs into a graduate-level discussion of genes, DNA, disease pathways, genetic-environmental interactions, availability of gene therapy, and clinical trials. The genetic counselor also makes the patient aware of other resources, such as disease-specific support groups, which may be developed by patients and families to provide support and practical knowledge.
In some cases, attention turns to at-risk relatives, and the genetic counselor may role-play with the patient to rehearse ways to share information with them. Genetic counselors may give patients a letter to distribute to family members with a copy of the patient’s test results, briefly explaining the condition identified and how relatives may find a genetic counselor in their area for their own risk assessment.
WHAT ABOUT GENETIC DISCRIMINATION?
Genetic discrimination is addressed in many genetic counseling sessions.
As defined by the National Human Genome Research Institute, genetic discrimination is “prejudice directed against people who have or may have a genetic disease.”27
In May 2008, the Genetic Information Nondiscrimination Act (GINA) was signed into law, providing some legal protections against genetic discrimination for patients undergoing predictive genetic testing. The law applies to most employers and health insurers but does not protect against discrimination by life or disability insurers. When discussing genetic testing, genetic counselors ensure that patients are aware of their rights and protections.
GINA would not be relevant for a patient who has a medical condition that may affect his or her insurability. For example, someone with thyroid cancer who is found to have an underlying gene mutation may still be denied any type of insurance coverage on the basis of his or her personal cancer diagnosis. However, should that person’s son who has not been diagnosed with cancer opt to undergo predictive testing, GINA would provide protection against employment and health insurance discrimination, as described above.
DIRECT-TO-CONSUMER GENETIC TESTING
As DNA technology has become increasingly complex, so has the task of understanding new tests and their clinical relevance to patients.
In the last several years, more companies have begun to offer direct-to-consumer genetic testing, which may be ordered without the involvement of a health care professional. While some companies hire or work closely with genetic counselors to conduct pretest and posttest genetic counseling, others do not, and preliminary research has found that only a minority of primary care physicians feel prepared to answer patients’ questions about direct-to-consumer genetic testing.28
Genetic counselors stay abreast of emerging technologies and are prepared to answer questions from patients who are considering or have already undergone such testing and from physicians who may wonder if a patient’s direct-to-consumer genetic testing results should affect his or her management.
Direct-to-consumer genetic testing will be discussed in depth in a future article in this series.
EXPLAINING ‘NORMAL’ (NEGATIVE) GENETIC TEST RESULTS
When testing results are normal, patients are educated about the meaning of “normal” results, the residual risk, and screening that might be appropriate in each person’s situation.
Sometimes a normal result does not mean the patient is not at risk for disease—for most diseases, genetic testing is not perfect and cannot identify a mutation in every at-risk family. Patients who have a family history of certain conditions may still face a higher risk despite normal test results. In these situations it is imperative that the family continue to adhere to follow-up recommendations even with normal test results.
Example: Marfan syndrome
Marfan syndrome is an autosomal dominant connective tissue disorder that, if unrecognized, is associated with significant morbidity and mortality. People with Marfan syndrome are at increased risk of aortic aneurysms, which can rupture spontaneously, leading to sudden death.
Although at least 70% of patients with Marfan syndrome have a mutation in FBN1, other patients meeting the clinical diagnostic criteria do not. Despite a normal genetic test result, they should adhere to the same screening guidelines as a person who tests positive.29
This concept—that screening should still be done despite a normal “Marfan test”—may be difficult for patients to grasp without a discussion of the imperfect sensitivity of genetic testing and of their real ongoing risks. Even more difficult to understand is the idea that the patient’s family members should also be screened as though they have the disease, given that the family’s mutation is unknown and predictive testing cannot be conducted.
Further complicating matters, other disorders such as Loeys-Dietz and vascular Ehlers-Danlos syndrome can mimic Marfan syndrome by causing aortic aneurysms, but management recommendations for them are very different.30,31
The appropriate genetic diagnosis for patients with aortic aneurysms can be facilitated by referring them to genetic counselors, who can identify appropriate testing. In this way, physicians can personalize medical management and give screening recommendations specific to the genetic disorder present.
EXPLAINING UNCERTAIN RESULTS
There are three possible results for most genetic tests—positive (a pathogenic or disease-causing mutation was found), negative (normal), and the frustrating “variant of uncertain significance” (VUS).
A VUS result means that an abnormality was detected in the gene, but that there are insufficient data about whether the abnormality alters the function of the gene in question and, thus, leads to disease. Since some gene variants are known to be common in the general population and not linked to disease and others are known to definitely alter a gene’s function and cause disease, a VUS that is clearly unknown poses a challenge not only to patient management, but also to family members seeking personal risk assessments.
Knowledge of how or if specific variants relate to disease is emerging. In time, some variants become reclassified as either disease-causing mutations or benign polymorphisms. However, careful consideration needs to be given to how to explain the abnormal result to the patient and to at-risk family members, as well as to how to explain the clinical implications of the VUS.
Example: Hereditary breast and ovarian cancer syndrome
People with hereditary breast and ovarian cancer syndrome face a lifetime risk of breast cancer of up to 87% and a risk of ovarian cancer of up to 44%. Most families with this syndrome have an inherited change in either the BRCA1 or BRCA2 gene.32,33 Given these risks, prophylactic mastectomy and oophorectomy are among the management options for mutation-positive patients. In the absence of clear genetic counseling, a patient with a VUS might see the “abnormal” test result and believe herself to be mutation-positive and thus at very high cancer risk.
An important role for the genetic counselor is to clarify the pathogenicity of a particular VUS. When a VUS is found, genetic counselors search for information about the variant by reviewing the medical literature, discussing it with the testing laboratory, arranging for family studies when appropriate, and contacting researchers whose work focuses on the gene in question.
Failure to properly research a particular VUS can lead to unnecessary and risky surgical procedures, as well as to falsely labelling relatives as being at risk. Until a VUS is reclassified as a disease-causing mutation, testing for it should not be offered to family members (unless through a research study), nor should medical management be based solely on the results of a particular VUS. In time, a VUS may be reclassified as either a benign polymorphism or a disease-causing mutation, and the genetic counselor will recontact the patient and physician with updated information and recommendations.
