7/29/2019 Genetic Testing Process Toolkit
1/7
Genetic Testing Process ToolkitInformed Consent & Pre-Test Counseling Checklist
Published September 201 NCHPEGAll rights reserved
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-paternityConsanguinityDifferent 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
7/29/2019 Genetic Testing Process Toolkit
2/7
Published September 2013 NCHPEG
All rights reserved
Benefits, Risks and Limitations of Genetic Testing
Potential Benefits Potential Limitations/Risks
Diagnose or identify the cause of a childs symptoms Possibility of uncertain variants or unanticipated results
(e.g., consanguinity, non-paternity)
End search for a diagnosis Possibility of a false negative or not coming to a
diagnosis; May not identify all possible gene mutations
Inform personalized management and treatment Treatment/management may not be clear with some
results
Provide prognostic information for the patient If predictive testing, not all patients with a gene
mutation will go on to develop the disease
Identity recurrence risk to other relatives 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 individualo No cause for neurologic symptoms identified in mutation-negative yet symptomatic individualo Guilt for potentially having passed on a mutationo Difficulty adjusting to an unanticipated incidental finding
Social issueso Child bearingo Selecting a careero Selecting a marriage partnero Screening in childhoodo Insurabilityo Employability
Resources
American Medical Association: Informed Consent
7/29/2019 Genetic Testing Process Toolkit
3/7
Genetic Testing Process ToolkitInformed Consent Tips & Talking Points
Published September 2013 NCHPEG
All rights reserved
Implications of a negative test result
Key Point Why is this Important for My Patient? Example
Like many other screening or diagnostic tests, thesensitivity 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 ofinterest that the testing was unable to detect, or
2. An alteration in another area of the genome notassessed on this test, which may be associated with
the syndrome of interest.
It is important for the family to understandthat 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.
A patient undergoes GFAP genetic testing for AlexanderDisease. 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 o f family members may be needed to ful ly interpret the test result
Key Point Why is this Important for My Patient? Example
It may be necessary to test other family members, such as
parents or siblings, to interpret the patients genetic
testing results.
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.
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.
7/29/2019 Genetic Testing Process Toolkit
4/7
Published September 2013 NCHPEGAll rights reserved
Clinically significant unanticipated findings
Key Point Why is this Important for My Patient? Example
Genetic testing can identify clinically important findings
unrelated to the reason for testing.
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.
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 Why is this Important for My Patient? Example
Genetic testing can reveal undisclosed family relationships. Families need to be informed that non-
paternity, or other potentially sensitive family
relationships such as consanguinity or incest,
can be revealed.
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, non-
paternity must be considered.
Payment & insurance pre-authorization
Key Point Why is this Important for My Patient? Example
Testing methods are complex and are evolving. Some
insurance companies will not cover genetic testing for thisreason, 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.)
Many families cannot afford to pay for
genetic testing out-of-pocket. It is importantto check with the insurance company before
testing is ordered to obtain approval before a
test is ordered to avoid financial hardship.
A patient has an insurance company that does not cover the
specific CPT codes that are associated with a genetic test. As aresult, the genetic test that was ordered is not covered by
insurance, and the patient gets a $1,500 bill.
7/29/2019 Genetic Testing Process Toolkit
5/7
Published September 2013 NCHPEGAll rights reserved
Risk of Genetic Discrimination
Key Point Why is this Important for My Patient? Example
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.
Families need to be aware of the existence
and limitations of GINA before testing is
done.
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 Why is this Important for My Patient? Example
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.
Some families may feel uncomfortable with
their genetic information, even if it is de-
identified, 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.
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 Why is this Important for My Patient? ExampleAt 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.
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.
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.
7/29/2019 Genetic Testing Process Toolkit
6/7
published July 2012
NCHPEG
All rights reserved
Genetic Testing Process ToolkitCollaborating 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 isalso appropriate forpatientsatincreasedriskwho do notwishtopursue genetic testing, andin
cases where the patientsriskstatus is uncertain. For questions about the need for referral, consult with the specialist.
Locating A Genetics ProfessionalAmerican College of Medical Genetics:www.acmg.net
National Society of Genetic Counselors:
www.nsgc.org
GeneTests Clinic Directory:
www.genetests.org
http://www.acmg.net/http://www.acmg.net/http://www.nsgc.org/http://www.nsgc.org/http://www.genetests.org/http://www.genetests.org/http://www.genetests.org/http://www.nsgc.org/http://www.acmg.net/7/29/2019 Genetic Testing Process Toolkit
7/7
published July 2012
NCHPEG
All rights reserved
Checklist for Collaboration with a Genetics ProfessionalHow 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/Histor y of Presenting Illness:
Developm ental History
On time () Delayed () Regression ()
Gross Motor
Fine Motor
Speech
Review of Systems and Physical Exam
() if normal
Constitutional Musculoskeletal
Eyes Skin
ENT/Audiology Psychiatric
Cardiovascular Endocrine
Respiratory Hematology
Gastrointestinal Allergy
Genitourinary Immunology
Comments:
Labs / Studies
Normal () Abnormal () If abnormal, explain
EEG
EMG
BAER
MRI
CT
LP
Metabolic
Genetic
Family History
() if
applicable
Describe relationship to patient
DD
MR/ID
Stroke
Headache/
Migraines
Seizures
Consanguinity
Other
Unremarkable