Genetic Testing Process Toolkit

Informed Consent & Pre-Test Counseling Checklist

Informed consent is an important step in the genetic testing process. In addition to being required by state laws and laboratories, thorough pre-test counseling will save you time when you discuss genetic testing results with the family. Discussion of these key points helps prepare the family for the potential outcomes and limitations of genetic testing. Use the accompanying handout on clinical examples and talking points for further illustration and practice.

Checklist
Communicate goals of testing Information about the test Purpose of testing Description of the disorder that will be tested for Ability of test to detect disease Potential benefits, risks, and limitations of testing See risks and benefits table (below) Confidentiality protections Genetic discrimination risks and protections Assess family goals and expectations Set Expectations Potential results Positive Negative Variant of uncertain significance May need parental/family testing Unanticipated results Non-paternity Consanguinity Different genetic alteration identified than anticipated (in whole genome analysis) Diagnosis unrelated to patients presentation (e.g., diagnosis of an adult-onset syndrome) Logistics of testing Payment and insurance pre-authorization Disclosure of results Phone vs. in person Who can results be disclosed to? Anticipated turn-around-time Potential specimen retention Document the informed consent discussion in the patients medical record

Published September 2013 NCHPEG All rights reserved

Benefits, Risks and Limitations of Genetic Testing

Potential Benefits Diagnose or identify the cause of a childs symptoms End search for a diagnosis Inform personalized management and treatment Provide prognostic information for the patient Identity recurrence risk to other relatives Potential Limitations/Risks Possibility of uncertain variants or unanticipated results (e.g., consanguinity, non-paternity) Possibility of a false negative or not coming to a diagnosis; May not identify all possible gene mutations Treatment/management may not be clear with some results If predictive testing, not all patients with a gene mutation will go on to develop the disease Increases anxiety Causes blame, guilt, or secrecy in the family Labels a patient with a diagnosis or specific risk, increasing concerns about discrimination

Psychological and social issues related to genetic testing The importance of psychosocial issues necessitate that the genetic counseling and informed consent process always accompany the genetic testing process. Most patients report being satisfied with their testing decisions Some degree of uncertainty associated with all test results that can result in anxiety Some patients may react negatively to either a positive or negative test result o Survivor guilt in a mutation-negative individual o No cause for neurologic symptoms identified in mutation-negative yet symptomatic individual o Guilt for potentially having passed on a mutation o Difficulty adjusting to an unanticipated incidental finding Social issues o Child bearing o Selecting a career o Selecting a marriage partner o Screening in childhood o Insurability o Employability

Resources
American Medical Association: Informed Consent

Published September 2013 NCHPEG All rights reserved

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 determine 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

Genetic Testing Process Toolkit

Collaborating with and referring to genetics
Genetic counseling is the process of helping people understand and adapt to the medical, psychological and familial implications of genetic contributions to disease. This process integrates risk assessment, education, and counseling. In some cases, it includes the offer and interpretation of genetic testing. The purpose is to help the patient and family to interpret and adapt to the genetic information, and make informed decisions based on his or her understanding of risks. Genetic counseling is best provided by specialists with knowledge and experience in clinical genetics, such as genetic counselors, physician geneticists, and advanced practice nurses trained in genetics. All providers, however, play a role in the genetic counseling process by: identifying patients who would benefit from genetic counseling, including patients who have personal or family histories suggestive of a hereditary syndrome; providing referral to genetic counseling services, informing patients about the reasons for and benefits of genetic counseling; helping patients identify what family medical information will be necessary for risk assessment; using the outcome of the genetics consultation to identify screening, risk reduction, and management plans; and answering questions for patients. Genetic counseling is also appropriate for patients at increased risk who do not wish to pursue genetic testing, and in cases where the patients risk status is uncertain. For questions about the need for referral, consult with the specialist.

Locating A Genetics Professional

American College of Medical Genetics: www.acmg.net National Society of Genetic Counselors: www.nsgc.org GeneTests Clinic Directory: www.genetests.org

published July 2012 NCHPEG All rights reserved

Checklist for Collaboration with a Genetics Professional

How to use this tool: This tool outlines the information you should include when referring a patient for genetic evaluation. You can print and fill it out for a patient, adapt it to use as a clinic form in your own practice, or transcribe the elements into an electronic referral form or template.
Reason for Referral/History of Presenting Illness:

Developmental History On time () Gross Motor Fine Motor Speech Review of Systems and Physical Exam () if normal Constitutional Eyes ENT/Audiology Cardiovascular Respiratory Gastrointestinal Genitourinary Comments: Musculoskeletal Skin Psychiatric Endocrine Hematology Allergy Immunology Delayed () Regression ()

Labs / Studies Normal () EEG EMG BAER MRI CT LP Metabolic Genetic Family History () if applicable DD MR/ID Stroke Headache/ Migraines Seizures Consanguinity Other Unremarkable Describe relationship to patient Abnormal () If abnormal, explain

published July 2012 NCHPEG All rights reserved