Genetic Counseling & Alport Syndrome

1. Genetic Counseling& Alport Syndrome Chelsea Alexander, MS, CGC Genetic Counselor University of Minnesota Medical Center Fairview

2. Overview • Genetic Counseling • Genetic Counseling in Alport Syndrome • Genetic Testing • Examples

3. What is a Genetic Counselor?

4. Educational Background of a Genetic Counselor • Master’s degree in human genetics or a related major • Certified by the American Board of Genetic Counseling • Qualified to work in a variety of settings: • clinics-(majority) • commercial labs • research labs • state health departments • pharmaceutical companies etc.

5. What is genetic counseling?

6. Family Questions… What is a “genetic condition”? What is genetic testing? What can this testing tell us? What does this result mean? What impact may this have on family members? How do we inform our family?

7. Genetic counseling is…. Genetic counseling is the process of helping people understand and adapt to the medical, psychological, and familial implications of the genetic contributions to disease. National Society of Genetic Counselors 2006

8. Role of Genetic Counselors • What is the chance of a genetic condition based on family and personal medical history (pedigree)? • What are important medical and family concerns? • Discuss, coordinate, and interpret genetic tests • Educate individuals about genetic conditions • Provide counseling/support regarding genetic information (implications for family members)

9. What else? • Provide supportive counseling, especially around time of new diagnosis, pregnancy, etc. • Serve as patient advocates (insurance, referrals). • Serve as a genetics resource. • Research related to medical genetics and genetic counseling.

10. Goals of Genetic Counseling • For Families and Individuals to: • Understand their family history and how it may be related to a condition • Discuss and understand the impact of genetic conditions on relatives and the immediate family • Participate in decision making about their medical care • Provide education that is meaningful for families • Discuss genetic testing options and implications • Assist with referrals to support groups and other health care providers

11. Genetic Counseling in Alport Syndrome? • See families at a time of: • New Diagnosis: Education, family history, inheritance, testing, resources and support • Genetic Testing: Coordinate, review test results and clinical meaning • Pregnancy: Partner carrier testing, reproductive options • Teens/Young adults: Age appropriate education, reproductive issues, etc

12. Genetic Testing • What is it? • A type of medical test (usually blood) that attempts to identify changes in chromosomes and/or genes. • May be used to attempt to confirm or rule out a suspected genetic condition. • Assist in determining a person’s chance of developing or passing on a genetic disorder. • Has both benefits and limitations. • What do results mean?

13. Genetic Information Nondiscrimination Act www.genomicslawreport.com/index • Title I: prohibits health insurers from requesting/requiring genetic information for decisions about coverage, premium rates, or preexisting conditions. • Title II: prohibits most employers from using genetic information in decisions of hiring, firing, or terms of employment.

14. What GINA does NOT do… • Routine tests that do not examine DNA, RNA or chromosomal changes. • Coverage does not extend to: • Life insurance • Disability insurance • Long-term care insurance • Not a mandate for coverage of tests. • Employment provisions generally do not apply for employers with >15 employees • Does not prohibit decisions based on manifestation of disease/disorder. • Some Federal Health Services

15. Example of genetic counseling

16. Pedigree symbols

17. Genetics “lingo” • DNA- Hereditary material in humans and almost all other organisms in the cell and is capable of self-replication • Gene- A hereditary unit consisting of a sequence of DNA that has a specific location on a chromosome and determines a particular characteristic in an organism. • Mutation/Gene Change- Change in the DNA sequence. • Pedigree- A chart of an individual's ancestors used in human genetics to analyze inheritance of certain traits, especially of familial diseases.

18. Norwegian/Finnish Native American/Irish microhematuria Microhematuria + proteinuria or renal failure

19. X-linked Recessive Norwegian/Finnish Native American/Irish microhematuria Microhematuria + proteinuria or renal failure

20. X-linked Inheritance • Genes located on the X chromosome • Women = two X chromosomes • Men = one X chromosome and one Y • COL4A5 gene in Alport syndrome: • A women can carry a gene change and usually may have hematuria, but some women experience more severe symptoms. • Fathers are not expected to pass X-linked traits to their sons.

21. Women with X-linked Alport syndrome: • 1 chance in 2 (50%) that a son will have Alport syndrome • 1 chance in 2 (50%) that a daughter will be a carrier like the mother

22. If the father has X-linked Alport syndrome: • All of his daughters will inherit the genetic change (carriers) and may or may not have symptoms. • None of his sons would be expected to have Alport syndrome.

23. Norwegian English/Irish microhematuria Microhematuria + proteinuria or renal failure

24. Autosomal Recessive Norwegian English/Irish microhematuria Microhematuria + proteinuria or renal failure

25. Autosomal Recessive • Recessive inheritance (at conception): • 25% chance of having a child with Alport syndrome • 50% chance of having a child who is a carrier • 25% chance of having a child who does not have Alport syndrome and is not a carrier • The parents of a child with Alport syndrome are obligate carriers • Approximately 50% of carriers exhibit persistent or intermittent microhematuria.

26. Italian English/Irish microhematuria Microhematuria + proteinuria or renal failure

27. Autosomal Dominant Italian English/Irish microhematuria Microhematuria + proteinuria or renal failure

28. Autosomal Dominant • 50% chance of having a child with Alport syndrome with each pregnancy • Not related to gender • Most individuals have an affected parent

29. Genetic Counseling Services • Genetic Counseling at UMMC • http://www.uofmmedicalcenter.org/Specialties/GeneticCounseling/S_044824 • Minnesota Genetic Counseling Association • MNGCA, http://mygenepool.org/ • National Society of Genetic Counselors • NSGC, http://www.nsgc.org/

30. References • R. Artuso, et al. Advances in alport syndrome diagnosis using next-generation sequencing. Euro J Human Genetics 2012; 20: 50-57. • M. Bekheirnia, et al. Genotype-phenotype correlation in X-linked alport syndrome. J. Am Soc Nephrol 2010; 21: 876-883. • J. Hertz, et al. Clinical utility gene card for: alport syndrome. Euro J Human Genetics 2012; 20. • M. Slajpah, et al. The importance of non-invasive genetic analysis in the initial diagnostics of alport syndrome in young patients. Pediatr Nephro 2005; 20: 1260-1264. • Genetests, http://www.ncbi.nlm.nih.gov • Genetics Home Reference, “Genetic Testing” • http://ghr.nlm.nih.gov/handbook/testing?show=all • NIH, http://www.genome.gov/24519851/ • National Society of Genetic Counselors, • www.nsgc.org