Genetics for the Primary Care Physician

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? A journal? A colleague? A Web site? Out of date Highly focused Expertise varies www.genetests.org FUNDED BY National Institutes of Health Contract No. N01-LM-3503 SPONSORING INSTITUTION University of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 Sequence analysis Mutation scanning and protein truncation testing (PTT) Protein truncation testing (PTT) Mutation Detection Rate up to 90% Test Availability ~80-~90% Clinical ~80% Duplication/deletion analysis Linkage ~8-12% If no mutation is detected, linkage testing can be considered in families with more than one affected member. 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 Tim 39 y Lisa 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 28 y 39 y Lisa 33 y FAP 50% risk Indeterminant risk 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 AK MI 63 y d. 35 y MVA TX CA 33 y TN 28 y Tim 39 y Lisa FAP 50% risk Indeterminant risk 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 Provider Genetics Professional Patient Staff 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 Suzanne B Cassidy, MD Mary Beth P Dinulos, MD Roberta A Pagon, MD Directories Genetic Counselors Laboratory Directory Coordinator Cynthia R Dolan, MS Roberta Spiro, MA Gina McCullough Grohs Aliya Hashemi Clinic Directory Coordinator Assistant Editors Resources Resources Liaison Kathi Marymee, MS Managing Editor Online Production Editor Editorial Assistant Monica Smersh Miriam Espeseth, MA Carla Gifford Technical Support Database Administrator Sergey Mikhaylov, MS Brad Willson Systems Administrator