Genetic Testing Process Toolkit

Informed Consent Tips & Talking Points

Implications of a negative test result

Key Point Like many other screening or diagnostic tests, the sensitivity of genetic testing is less than 100%. A normal or negative result could be a false negative, and does not rule out: 1. the possibility of an alteration in this gene/area of interest that the testing was unable to detect, or 2. An alteration in another area of the genome not assessed on this test, which may be associated with the syndrome of interest. Why is this Important for My Patient? It is important for the family to understand that a negative test result does not rule out the possibility that the patient has the suspected genetic syndrome or a related disorder. Genetic testing can produce results that require additional testing or interpretation. Example A patient undergoes GFAP genetic testing for Alexander Disease. The laboratory test is not designed to detect mutations in the promoter region of the gene. If patient has a mutation in the promoter region, this would explain her clinical diagnosis of Alexander disease based on MRI findings and clinical presentation, but it would not be detected by this particular test.

Testing of family members may be needed to fully interpret the test result
Key Point It may be necessary to test other family members, such as parents or siblings, to interpret the patients genetic testing results. Why is this Important for My Patient? Parents need to understand that a test result may not provide a final answer and that genetic tests require interpretation and familial samples in some cases. Example A patient is found to have two novel (never seen before) and unclassified (may or may not be pathogenic) mutations in the GJC2 gene, which is associated with Pelizeaus Merzbacher Like Disease (PMLD). PMLD is a recessive disorder. Further testing is needed to determine if these two mutations are in cis (on the same chromosome) or in trans (on opposite chromosomes). If they are in cis, then these mutations do not explain the patients symptoms. The best way to determin e whether two mutations are in cis or trans is to test the parents to confirm that each carries one of the mutations.

Published September 2013 NCHPEG All rights reserved

Clinically significant unanticipated findings

Key Point Genetic testing can identify clinically important findings unrelated to the reason for testing. Why is this Important for My Patient? It is important for the family to understand that test results may have implications outside of providing a diagnosis, and in fact, they might learn unanticipated information without learning anything about the etiology childs disease. Example Your patient undergoes genetic testing for multiple nuclear genes involved in mitochondrial function. Testing reveals a single heterozygous mutation in one of these genes. Because all of the genes in this panel are associated with recessive diseases, this does not provide a diagnosis. Rather, this result indicates that this patient is a carrier of a genetic condition that affects mitochondrial function. This could have reproductive implications for this patients and her parents future.

Undisclosed family relationships

Key Point Genetic testing can reveal undisclosed family relationships. Why is this Important for My Patient? Families need to be informed that nonpaternity, or other potentially sensitive family relationships such as consanguinity or incest, can be revealed. Example A patient is diagnosed with Tay-Sachs disease, an autosomal recessive disorder. The patient has compound heterozygous mutations, but confirmatory parental testing only identifies the patients mother to be a carrier. The father is not a carrier. While there is a possibility of a de novo mutation, nonpaternity must be considered.

Payment & insurance pre-authorization

Key Point Testing methods are complex and are evolving. Some insurance companies will not cover genetic testing for this reason, and letters of appeal may need to be written by to argue for the clinical utility of the testing despite the potential limitations of the testing. (Consider obtaining pre-authorization for genetic testing from the patients insurance company before ordering a genetic test.) Why is this Important for My Patient? Many families cannot afford to pay for genetic testing out-of-pocket. It is important to check with the insurance company before testing is ordered to obtain approval before a test is ordered to avoid financial hardship. Example A patient has an insurance company that does not cover the specific CPT codes that are associated with a genetic test. As a result, the genetic test that was ordered is not covered by insurance, and the patient gets a $1,500 bill.

Published September 2013 NCHPEG All rights reserved

Risk of Genetic Discrimination

Key Point While GINA is in place to prevent discrimination based on genetic information, there are still opportunities for this type of discrimination to occur. Parents/patients should take this into account when deciding whether or not to consent to a genetic test. Genetic counseling can help elucidate the types of genetic information that may be revealed that may be potentially problematic for family members. Why is this Important for My Patient? Families need to be aware of the existence and limitations of GINA before testing is done. Example An 18-year old patient undergoes genetic testing to determine if she has inherited her fathers trinucleotide repeat expansion, which causes Huntingtons disease in her family. She receives a positive result. Although GINA protects this patient from employment and health insurance discrimination, this patients life insurance premiums can still increase. Also, if she is found to have onset symptoms, even very subtle ones, health insurance and employment discrimination may still be a risk.

Potential specimen retention

Key Point Many labs use stored DNA for their own research efforts. For questions relate to the type of research done on stored samples, contact the lab if a patient/parent wants additional information before deciding whether or not to allow a sample to be stored for research. Why is this Important for My Patient? Some families may feel uncomfortable with their genetic information, even if it is deidentified, being used for reasons unrelated to their own health. It is important that families understand that they have a choice whether or not to allow the lab to keep and use their samples. Example A genetic testing lab uses de-identified patient samples as controls to perform quality control tests for their newly developed genetic tests.

Plan for results disclosure

Key Point At the time that the sample is sent for testing, it may be good practice to set up a time for the patient/parent to come back to clinic for results disclosure around the time the test results are expected to be available. Having an appointment set up for this can facilitate an expected and dedicated time for discussing the implications of positive, negative, and uncertain testing results. Why is this Important for My Patient? For diagnoses that are potentially devastating, it is important for families to have clear expectations of how and when they will receive results. This eliminates the anxiety and agony that patients may feel while waiting for a phone call. It also allows families to activate their emotional support networks so that friends/families/clergy/etc. are available at the time of results disclosure. Example A patient undergoes genetic testing for neronal ceriod lipofucionosis. The test comes back positive. Based on the knowledge that the testing has a turn-around time of 4-6 weeks, you have set up a time 6 weeks from the time the test was sent for the family to come back to the clinic to receive the results from you in person.

Published September 2013 NCHPEG All rights reserved

Published September 2013 NCHPEG All rights reserved