1. The Primary Care Physician: The Primary Source of Genetic Testing Information Copyright University of Washington 2007

2. 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?”

3. 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?

4. 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? Genetic Testing

5. 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

6. 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Out of date A journal?Highly focused A colleague?Expertise varies A Web site?

7. www.genetests.org FUNDED BY National Institutes of Health Contract No. N01-LM-3503 SPONSORING INSTITUTION University of Washington Seattle, WA

9. 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

10. International Laboratory Directory 615 Clinical and research laboratories 1370 Inherited diseases 1080 clinical tests ~290 research only

11. Genetics and prenatal diagnosis clinics United States: ~ 1000 clinics International: ~ 100 clinics

12. 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

13.   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

15. FAP

18. Summary Diagnosis Clinical Description Differential Diagnosis Management Genetic Counseling Molecular Genetics Resources References

19. 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

20. 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) ACP-Associated Polyposis Conditions

21.   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

22. 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 ACP-Associated Polyposis Conditions

23.   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

24. 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?

25.   Cytogenetic   DNA   Metabolic Types of Genetic Tests

26. Test Method Mutation Detection Rate Test Availability Sequence analysis up to 90% Mutation scanning and protein truncation ~80-~90% Clinical testing (PTT) Protein truncation ~80% testing (PTT) Duplication/deletion~8-12% analysis Molecular Genetic Testing Direct DNA tests Linkage If no mutation is detected, linkage testing can be considered in families with more than one affected member. ACP-Associated Polyposis Conditions

27. mutation scanning

28. de novo mutation

29. 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?

30. Diagnostic Predictive Carrier Prenatal Screening Uses of Genetic Testing

31. FAP 50% risk 10 y 39 y Jay Lisa Tim

32. Uses of Genetic Testing Diagnostic Predictive Carrier Prenatal Screening

33. 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

34. Management Surveillance: Family members who have not inherited the disease- causing mutation: Routine colon cancer screening beginning at age 50 years ACP-Associated Polyposis Conditions

35. Testing Strategy Test Tim Mutation detected Direct testing useful Proceed with testing family Direct testing not useful Do not proceed with testing family No mutation detected STOP

36. 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?

37. FAP

38. Hierarchical Search Result

41. 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?

42. 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

43. 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?

44. FAP Jay 10 y 39 y 33 y 28 y d. 35 y MVA 63 y Indeterminant risk 50% risk Amy 6 y Sarah 14 y Tim Lisa

45. 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

46. 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 Genetics Professionals

47. 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

48. Testing Strategy Test Tim Direct testing not useful Proceed with No mutation detected STOP genetic counseling surveillance of all at-risk relatives

49. FAP Jay 10 y 39 y 33 y 28 y d. 35 y MVA 63 y Indeterminant risk Amy 6 y Sarah 14 y 50% risk Tim Lisa AK MI TX CATN

52. Clinic Search Result

53.   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

60. Genetics Professional Patient Primary Care Provider Genetic Counseling and Testing

61. 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 Suzanne B Cassidy, MD Mary Beth P Dinulos, MD Monica Smersh Miriam Espeseth, MA Carla Gifford Editor-in-Chief Associate Editors Assistant Editors Managing Editor Online Production Editor Editorial Assistant Genetic Counselors Laboratory Directory Coordinator Clinic Directory Coordinator Cynthia R Dolan, MS Roberta Spiro, MA Gina McCullough Grohs Aliya Hashemi Database Administrator Systems Administrator Sergey Mikhaylov, MS Brad Willson Staff GeneReviews Principal InvestigatorRoberta A Pagon, MD Directories Technical Support Resources Resources Liaison Kathi Marymee, MS