Genetic Counseling 101 TCHAPP Conference February 7, 2014

1. Sarah Scollon, MS, CGC Certified Genetic Counselor Genetic Counseling 101TCHAPP ConferenceFebruary 7, 2014

2. Objectives 1. The role of a genetic counselor. 2. Identifying patients who would benefit from a genetics evaluation. 3. How a genetics evaluation can affect the care of your patient.

3. What is a Genetic Counselor? • Health professionals with specialized graduate degrees and experience in the areas of medical genetics and counseling. • Members of a health care team, providing information and support to families who have members with congenital anomalies or genetic disorders and to families who may be at risk for a variety of inherited conditions. www.nsgc.org

4. Roles of a Genetic Counselor • Identify families at risk. • Investigate the problem present in the family. • Interpret information about the disorder. • Analyze inheritance patterns and risks of recurrence. • Review available options with the family. www.nsgc.org

5. Roles of a Genetic Counselor • Provide supportive counseling to families. • Serve as patient advocates and refer individuals and families to community or state support services. • Serve as educators and resource people for other health care professionals and for the general public. www.nsgc.org

6. Educational Background • Enter the field from a variety of disciplines, including biology, genetics, nursing, psychology, public health, and social work.  • Masters Degree (typically a 2 year training program) • Currently 34 colleges and universities across the United States and Canada with master's degree programs in genetic counseling. • Typical class size is 4-8 students • UT Houston has a program • Board Certification • Licensure available in 18 states (not available in Texas)

7. Coursework • Academic coursework • medical genetics, epidemiology, statistics, cytogenetics, counseling theory, ethics, etc. • Clinical experience • clinical rotations throughout training • clinical internship rotation during the summer between first and second year • must fulfill logbook requirements • Thesis project

8. “Traditional” Settings • Prenatal Genetics • General Pediatric Genetics • Adult Genetics • Cancer Genetics (primarily adults)

9. Expanding Roles of Genetic Counselors • Laboratory • Industry/Sales • Metabolic • Education • Cardiology • Research • Neurogenetics • ART/Infertility • PGD • Public Health • Newborn Screening • Hematology • Ethical, legal, social (ELSI) • Psychiatric • Teratology • Support Groups

10. Which Patients Should I Refer?

11. Family History • 3 Generation pedigree • Congenital anomalies • Intellectual disability • Diseases that run in the family and ages of diagnosis • Early deaths • Consanguinity • Ethnicity

12. General Pediatric Genetics • Reasons for referral: • Abnormal newborn screening • Metabolic disorders • Intellectual disability/developmental delays • Growth disorders/Skeletal dysplasia • Multiple congenital anomalies • Physical features suggestive of genetic disorder (i.e café au lait spots in neurofibromatosis type 1) • Family history of a genetic disorder

13. Texas Children’s Pediatric Genetics Clinic Referral can be made in EPIC with Genetics referral form Phone:832-822-4280 Fax: 832-825-4294

14. Case Examples • 3 month old male presents with a failed newborn hearing screen and follow-up audiology exam showing sensorineural hearing loss. The family reports no family history of hearing loss. • 6yr old male with a history of congenital heart disease and delayed milestones. Family is worried as his teachers are now raising concerns for learning difficulties in school.

15. Pediatric Cancer Genetics • Reasons for referral: • High risk tumors (i.e. retinoblastoma, adrenocortical carcinoma, rhabdoid/ATRT, rhabdomyosarcoma before age 3) • Family history of cancer especially with early ages of onset • Diagnosis of cancer along with developmental delay or congenital anomalies • Polyposis conditions • Physical findings suggestive of genetic condition (i.e. skin findings with cancer)

16. Baylor Pediatric Cancer Genetics Clinic Staff message or email: splon@txch.org sxscollo@txch.org Phone: 832-824-4685 Fax: 832-825-4276

17. Case example • 9yr old male diagnosed with glioblastoma. Upon physical exam you note hyperpigmented macules. His mother had been diagnosed with endometrial cancer at the age of 37yrs. His father reports a family history of colon cancer in several of his relatives. • 7yr old female originally presented because parents had noticed several episodes of bloody stools. She has since seen GI where a colonoscopy was performed and juvenile polyps were detected.

18. Prenatal • Preconception • Pre-implantation Genetic Diagnosis (PGD) • Infertility • Abnormal screens/ultrasounds • Teratogens • Advanced maternal age • Carrier screening/status • Known genetic disease in the family • Child recently diagnosed with genetic condition

19. Baylor Prenatal Clinic • Complete an EPIC order (MFM) or request for services form. • http://women.texaschildrens.org/MFM • Phone: (832-826-7500) • Fax: 832-825-9402 • prenatalgenetics@texaschildrens.org

20. Case Examples • At a well child check for a 3yr old female, her mother informs you she is pregnant. She brings up a concern in her family history. She explains that her brother has intellectual disabilities. Recently her sister’s son was diagnosed with Fragile X syndrome. She is concerned for the risk to her daughter and her current pregnancy. • You currently follow a family with a 4 year old son with known sickle cell trait. After an anemia work-up for his 2yr old brother the family was surprised to learn he has beta thalassemia trait. They are currently considering their 3rd pregnancy.

21. Adult Genetics Clinic • Neuromuscular disorders • Huntington’s disease • Early onset Alzheimer’s disease • Connective tissue disorders • Cardiovascular disease • Adult Cancers

22. Baylor Adult Genetics Clinic Referrals: (P): 713-798-7820 (F:): 703-798-6450 EPIC referral for Adult Genetics

23. Case Examples • 7yr old female presents to clinic with a fever. You are saddened to learn that her mother was recently diagnosed with breast cancer at the age of 27yrs. Her doctor ordered BRCA testing and she is negative. She shares with you an extensive family history of cancer including her mother dying of breast cancer in her 30s, an uncle with sarcoma and a nephew recently diagnosed with a brain tumor. She is very concerned for the risk of cancer in her daughter. • You meet with a young family for their son’s well child visit. When you review the family history the father shares that his grandfather had suffered from Huntington’s disease. His own father is now beginning to show signs of the disease. He understands he may be at risk and is concerned for his son. However, he is not sure he would want to know this information himself.

24. What about Insurance Coverage? • Genetic testing often must go through a pre-authorization process with insurance • Letters of medical necessity • Peer to peer review • Change in CPT codes in 2013 • Newer technologies not always covered

25. Introducing the Idea of a Genetics Referral • Barriers: • Beliefs about genetics • Affects the family unit • Issues of guilt/blame • Raise concerns for the future • Concerns about genetic testing and privacy

26. What about Privacy? Genetic Information Nondiscrimination Act (GINA) of 2008 • Federal law • Protects people from genetic discrimination in health insurance and employment. • Cannot use genetic information to: • Make decisions about eligibility for health insurance • Make decisions about health insurance premium, contribution amounts, or terms of coverage • Hiring, firing, promotion or pay • Limit, segregate, classify or otherwise mistreat an employee www.ginahelp.org

27. What does GINA not cover? • Current Health Status • Insurance: • U.S. military who receive their care through Tricare. • Veterans who receive care through the veterans administration • The Indian Health Service • Federal employees enrolled in Federal Employee Health Benefits Plan • Employment: • U.S. military and federal employees • Employers with fewer than 15 employees www.ginahelp.org

28. www.ginahelp.org

29. How will a genetic evaluation benefit my patient?

30. What will happen at the visit? • Family may receive a phone call prior to the visit to gather family or medical history information • On the day of the visit: • Physical examination • Detailed medical history • Discussion of genetic testing options if appropriate • Blood draw for genetic testing may occur • All genetic testing is optional • Following the visit: • May need to obtain medical records • Referral to specialist for further investigation • See family back in future

31. The Role of a Genetic Counselor in the Visit • Case preparation • Most often see patient with physician (in many settings counselors are unable to bill or sign orders) • Obtain family history/medical history • Explain genetic concepts/testing to the family • Provide psychosocial support • Explain inheritance and reproductive options • Identify resources/support organizations for the family

32. Genetic Testing

33. Standard Karyotype

34. Beyond the Karyotype (Single Gene) • Sequencing: Reads through gene letter by letter. • Deletion/Duplication analysis: Looks for missing or extra pieces of the gene.

35. Beyond Single Gene Testing • Chromosomal Microarray (CMA): Analyzes changes in copy number over a large number of genes simultaneously. • Next Generation Sequencing: New sequencing technology that allows for mass parallel sequencing of thousands of genes at once.

36. Chromosomal Microarray https://www.bcm.edu/cancergeneticslab/index.cfm?pmid=14209

37. Possible Results • Testing in Proband (first family member tested) • Positive- A change in the gene was identified that is know to cause disease. • Negative-A change in the gene was not identified. • Variant of Unknown Significance- A change in the gene was identified that is rare or has never been seen before. The clinical significance of the change is unknown. • Parental studies • Familial studies • No clinical action at this time. • Known familial mutation: yes or no answer

38. Familial Mutation Testing • Important to determine if genetic testing has been performed in previous family members. • If mutation is known in the family, testing for ONLY the familial mutation is required. • Comprehensive testing is NOT required. • Known mutation testing is often significantly less expensive.

39. Predictive Genetic Testing for Adult Onset Conditions in Children • i.e. adult onset cancer syndromes, adult onset neurological disorders, Huntington disease. • “Angela Jolie Effect” • Standard of care has been NOT to test minors until adulthood. • Screening (if any) typically does not begin until the early to mid-20s or 10 years before the earliest diagnosis in the family • Ask families to consider the effects of this information on the child • Medical exceptions • Technical report: Ethical and Policy Issues in Genetic Testing and Screening of Children. ACMG policy statement. March 2013

40. Genetic Testing Turnaround • Most often a blood draw (in some cases a skin biopsy may be needed). • Standard genetic testing: 4-6 weeks • Familial genetic testing: 3-4 weeks • Panel testing/ whole exome sequencing: approx 3 months

41. Expanding Roles in the Genomic Era • Whole exome sequencing became clinically available at the end of 2011 • Allows sequencing of all 20,000 genes at once • Decreasing “diagnostic odyssey” • Incidental findings • Whole Genome Sequencing on the horizon

42. Whole Exome Sequencing Outcomes • Baylor Medical Genetics Laboratory reported in New England Journal of Medicine on first 250 patients for whom whole exome sequencing was ordered. • Approximately 80% were children with neurological phenotypes. • Reported 25% molecular diagnostic rate.

43. Roles of Genetic Counselors in Genomics • Creating recommendations for informed consent • Laboratories • Part of multidisciplinary teams interpreting variants • Return of Results • Research

44. BASIC3 BaylorAdvancingSequencingIntoChildhoodCancerCare NHGRI RFA-HG-10-017 Clinical Sequencing Exploratory Research (U01) Cancer Risk? GBM Sharon E. Plon, MD, PhD (PI) Will Parsons, MD, PhD (PI) Stacey Berg, MD (co-Investigator) Murali Chintagumpala, MD (co-Investigator)

45. What can the referring provider expect? • Referring providers and PCPs are informed of the outcomes of consult and results of genetic testing. • Recommendations based on consult will be provided to referring physician/PCP. • Family is provided with a genetic counseling letter and a copy of results for their records.

46. Benefits of a Genetic Diagnosis • May answer the question, “why?” for the family • Can provide guidance for screening/surveillance • A genetic diagnosis may help with obtaining services • Identify potential treatment options • Identify other family members at risk/not at risk • Family planning

47. Screening and Prevention in Action • Skeletal Dysplasia Clinic • Metabolic Clinic • Neurofibromatosis Clinic • Cardiovascular Genetics Clinic • Cancer Screening and Prevention Clinic

48. References and Resources References • National Society of Genetic Counselors- www.nsgc.org • American College of Medical Genetics- www.acmg.net • American Board of Genetic Counseling- www.abgc.org • Ross L, Saal H, David K et all. Technical Report:ethical and policy issues in genetic testing and screening of children. Genetics in Medicine. March 2013; 15(3): 234-245 • Uhlmann, Wendy, Schuette, Jane L. , Yashar, Beverly, Eds. A Guide to Genetic Counseling. Hoboken, NJ. John Wiley and Sons, Inc. 2009. 2nd edition. • Yang Y, Muzny DM, Reid JG et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med. 2013 Oct 17;369(16):1502-11. Epub 2013 Oct 2. • www. ginahelp.org Resources • Genereviews www.genetests.org/by-genereview/ • My46- www.my46.org/learning-center • Newborn Screening Fact Sheets: www.newbornscreening.info/Parents/facts.html

49. Acknowledgements • Texas Children's Hospital Advanced Practice Provider Conference organizers • Dr. Sharon Plon • Baylor/TCH Genetic Counselors