The Primary Care Physician:
The Primary Source
of Genetic Testing Information
Copyright University of Washington 2007
Imagine this…
Dr. Step is wrapping up the summer camp physical for his
10 year-old patient, Jay. He has addressed Jay’s
 Warts
 Emerging myopia
 Safety counseling
Time is up.
Jay’s mother, Lisa, stands up to leave and says, “By the
way, my husband, Tim, has just been diagnosed with colon
cancer, and his doctors are calling it familial adenomatous
polyposis. I heard there is a genetic test for FAP. Should
Jay be tested?”
Genetic Counseling
• What is FAP and what causes it?
• Who else in the family could get FAP?
• Should we be tested for FAP?
• How can we cope with FAP?
Genetic Testing
• What kind of genetic test is it?
• How would the genetic test be used?
• Where can I find a lab that does the test?
• What is involved in ordering this genetic test?
• How can I answer all the questions that the
family has?
Where is Lisa going to go
for an answer?
71% of American adults say they would most
likely ask their primary care physician about a
genetic disorder present in their family.
Genetic Testing: A study of consumer attitude
AMA March 1998
Where is Dr. Step going to go
for answers?
A text book?
Out of date
A journal?
Highly focused
A colleague?
Expertise varies
A Web site?
www.genetests.org
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National Institutes of Health
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SPONSORING INSTITUTION
University of Washington
Seattle, WA
GeneReviews
• Genetic disease descriptions
• >380 Reviews (April 2007)
• One new Review added each week
• Expert-authored, peer-reviewed
• Current information on genetic test use in diagnosis,
management, genetic counseling
• Links to genomic databases, patient resources,
PubMed citations, policy statements/guidelines
International Laboratory Directory
615 Clinical and research laboratories
1370 Inherited diseases
• 1080 clinical tests
• ~290 research only
Genetics and prenatal diagnosis clinics
• United States: ~ 1000 clinics
• International:
~ 100 clinics
Educational Materials
• Genetic counseling and testing concepts
• PowerPoint slide show presentations on genetic
testing resources
• Illustrated Glossary of >220 terms
• Links to GeneticTools, a curriculum for teachers of
primary care physicians
Genetic Counseling
 What is FAP and what causes it?
 Who else in the family could get FAP?
 Should we be tested for FAP?
 How can we cope with FAP?
FAP
Summary
Diagnosis
Clinical Description
Differential Diagnosis
Management
Genetic Counseling
Molecular Genetics
Resources
References
ACP-Associated Polyposis Conditions
Summary
Disease description
• Colon cancer syndrome
• Polyps develop 7-36 years
• Colon cancer at 34-43 years
Diagnosis/testing
• Caused by mutations in APC
• 95% of patients have identifiable APC mutations
Genetic counseling
• Autosomal dominant
ACP-Associated Polyposis Conditions
Clinical Description
• Colorectal adenomatous polyps: average 16 years
• Colon cancer: average 39 years
• Other features: osteomas, dental abnormalities,
desmoid tumors
• Extra-colonic cancers (small bowel, stomach, pancreas
thyroid, CNS, liver, bile ducts)
Genetic Counseling
 What is FAP and what causes it?
 Who else in the family could get FAP?
 Should we be tested for FAP?
 How can we cope with FAP?
ACP-Associated Polyposis Conditions
Genetic Counseling
Mode of Inheritance
• Autosomal dominant
Risk to Family Members
Parents of a proband.
• 75-80% of probands have an affected parent
• 20-25% have a de novo mutation
Sibs of a proband.
• If a parent has FAP, risk is 50%
• If neither parent has FAP, risk is low
Offspring of a proband.
• 50% risk
Genetic Counseling
 What is FAP and what causes it?
 Who else in the family could get FAP?
 Should we be tested for FAP?
 How can we cope with FAP?
Genetic Testing





What kind of genetic test is it?
How would the genetic test be used?
Where can I find a lab that does the test?
What is involved in ordering this genetic test?
How can I answer all the questions that the
family has?
Types of Genetic Tests
 Cytogenetic
 DNA
 Metabolic
ACP-Associated Polyposis Conditions
Molecular Genetic Testing
Direct DNA tests
Test Method
Mutation Detection Rate
Sequence analysis
up to 90%
Mutation scanning
and protein truncation
testing (PTT)
~80-~90%
Protein truncation
testing (PTT)
~80%
Duplication/deletion
analysis
~8-12%
Linkage
If no mutation is detected, linkage testing can be considered in families
with more than one affected member.
Test Availability
Clinical
mutation scanning
de novo mutation
Genetic Testing






What kind of genetic test is it?
How would the genetic test be used?
How is the genetic test applied in this situation?
What is involved in ordering this genetic test?
How can I answer all the questions that the
family has?
Uses of Genetic Testing
Diagnostic
Predictive
Carrier
Prenatal
Screening
Lisa
Tim
39 y
10 y
Jay
FAP
50% risk
Uses of Genetic Testing
Diagnostic
Predictive
Carrier
Prenatal
Screening
ACP-Associated Polyposis Conditions
Management
Molecular genetic testing: By age 10-12 years
Surveillance: Persons with an APC mutation or at-risk for FAP
who have not undergone molecular genetic testing:
• Annual sigmoidoscopy beginning at age 10-12 years
Colectomy: When polyps appear
ACP-Associated Polyposis Conditions
Management
Surveillance: Family members who have not inherited the diseasecausing mutation:
• Routine colon cancer screening beginning at
age 50 years
Testing Strategy
Test Tim
Mutation detected
• Direct testing useful
• Proceed with testing family
No mutation detected
STOP
• Direct testing not useful
• Do not proceed with testing family
Genetic Testing





What kind of genetic test is it?
How would the genetic test be used?
Where can I find a lab that does the test?
What is involved in ordering this genetic test?
How can I answer all the questions that the
family has?
FAP
Hierarchical Search Result
Genetic Testing





What kind of genetic test is it?
How would the genetic test be used?
Where can I find a lab that does the test?
What is involved in ordering this genetic test?
How can I answer all the questions that the
family has?
Ordering Genetic Testing
Genetic tests may be ordered by any physician.
•
•
•
•
Choosing a laboratory
Pretest counseling and informed consent
Sample logistics and supporting documentation
Test result interpretation and follow-up
Genetic Testing





What kind of genetic test is it?
How would the genetic test be used?
Where can I find a lab that does the test?
What is involved in ordering this genetic test?
How can I answer all the questions that
the family has?
63 y
d. 35 y
MVA
Tim
33 y
FAP
50% risk
Indeterminant risk
28 y
Lisa
39 y
Sarah
14 y
Jay
10 y
Amy
6y
Genetics Consultation
A genetics consultation involves care of an individual
or family to: Providing or arranging for psychosocial support
• Confirm, diagnose or rule out a genetic condition
• Identify / arrange for medical management
• Calculate and communicate genetic risks
• Provide or arrange psychosocial support
Genetics Professionals
Medical Geneticists (MD, PhD)
Certified by: American Board of Medical Genetics
Genetic Counselors (MS)
Certified by: American Board of Genetic Counseling
and/or American Board of Medical Genetics
Testing Strategy
Test Tim
Mutation detected
• Direct testing useful
• Proceed with
genetic counseling
• genetic testing of all at-risk relatives
• surveillance of mutation-positive relatives only
•
Testing Strategy
Test Tim
No mutation detected
STOP
• Direct testing not useful
• Proceed with
• genetic counseling
• surveillance of all at-risk relatives
MI
AK
63 y
CA
33 y
FAP
50% risk
Indeterminant risk
TX
d. 35 y
MVA
TN
28 y
Tim
Lisa
39 y
Sarah
14 y
Jay
10 y
Amy
6y
Clinic Search Result
Genetic Counseling
 What is FAP and what causes it?
 Who else in the family could get FAP?
 Should we be tested for FAP?
 How can we cope with FAP?
Genetic Counseling and Testing
Primary Care
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Principal Investigator
GeneReviews
Editor-in-Chief
Associate Editors
Roberta A Pagon, MD
Thomas D Bird, MD
Cynthia R Dolan, MS
Gerald L Feldman, MD, PhD
Richard JH Smith, MD, PhD
Karen Stephens, PhD
Assistant Editors
Suzanne B Cassidy, MD
Mary Beth P Dinulos, MD
Managing Editor
Monica Smersh
Roberta A Pagon, MD
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Roberta Spiro, MA
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