Self-pay, expanded carrier screening Developed by Ms. Shawna Morrison, Dr. June Carroll, and Dr. Judith Allanson Last updated May 2016

Disclaimer This presentation is for educational purposes only and should not be used as a substitute for clinical judgement. GEC-KO aims to aid the practicing clinician by providing informed opinions regarding genetic services that have been developed in a rigorous and evidence-based manner. Physicians must use their own clinical judgement in addition to published articles and the information presented herein. GEC-KO assumes no responsibility or liability resulting from the use of information contained herein.

Objectives Following this session the learner will be able to: – Refer to their local genetics centre and/or order genetic testing appropriately regarding private, physician ordered genetic testing – Discuss and address patient concerns regarding private, physician ordered genetic testing – Find high quality genomics educational resources appropriate for primary care

Self-pay, expanded carrier testing supports patient autonomy and may help some couples avoid long wait times for genetics consults Physicians ordering testing need to be informed about the conditions on the panels and prepared to provide both pre- and post-test counselling Currently expanded carrier screening is not standard of care Pearls

Case 1: Julie and Chris A healthy non-consanguineous newlywed couple Both are 33 years old Chris is of German and English ancestry and he believes there may be some Ashkenazi Jewish ancestry Julie is of French Canadian and Northern European ancestry Planning to start their family

Case 1: Julie and Chris Julie’s cousin, Jean, is the same age and also recently married Jean was offered a family planning carrier screening panel which was partly covered by her health insurance Jean lives in Boston, MA

Case 1: Julie and Chris Julie would also like to have this panel and understands that she would have to pay for the test herself She needs you to order the test She has brought all the completed paperwork to you Physician signature here______________

Why carrier screening? To facilitate informed reproductive decision making by identifying couples at risk of having an affected child with a recessive disorder Ideal timing is during the preconception period Henneman et al., 2015 Eur J Hum Genet Allows for:  Greatest number of options  More time for informed decision making

What are Canadian recommendations for ethnicity- based carrier screening? Geneticseducation.ca > Point of Care Tools > Ethnicity-based screening in Canada

What are Canadian recommendations for ethnicity- based carrier screening?

Geneticseducation.ca > Point of Care Tools > Ethnicity-based screening in Canada What are Canadian recommendations for ethnicity- based carrier screening?

SOGC.org > Clinical Practice Guidelines > Genetics What are Canadian recommendations for ethnicity- based carrier screening? May 2016 Watch for updated recommendations by the Society of Obstetricians and Gynaecologists of Canada

Geneticseducation.ca > Genetics Centres What are Canadian recommendations for ethnicity- based carrier screening? Connect with your local genetics centre for more on your local population e.g. French Canadians from Saguenay-Lac-Saint-Jean or Charlevoix regions

Why expanded carrier screening? Individuals are screened regardless of ancestry or geographic origin (‘pan-ethnic’ or ‘universal’ screening) Leads to the detection of more carriers and carrier couples Henneman et al., 2015 Eur J Hum Genet Technology is advancing and costs are decreasing

Self-pay, expanded carrier screening

Is not standard of care Does not replace current screening guidelines Self-pay, expanded carrier screening

Pre-test counselling  Are voluntary  Screen for conditions of variable severity  Screen for conditions with different modes of inheritance e.g. not all are recessive  Assume accurate paternity for risk assessment  Do not rule out risk in the event results are negative  May be diagnostic or reveal information about an individual’s personal health  Are voluntary  Screen for conditions of variable severity  Screen for conditions with different modes of inheritance e.g. not all are recessive  Assume accurate paternity for risk assessment  Do not rule out risk in the event results are negative  May be diagnostic or reveal information about an individual’s personal health Patient is aware that expanded carrier screening panels:

Pre-test considerations May be an option to not screen for all available conditions Consider excluding: Disorders which usually present in adulthood and genetic testing cannot distinguish between childhood or adult onset (e.g.  1-antitrypsin deficiency) Genes where variants have low/no clinical utility (e.g. MTHFR) Conditions where the most appropriate approach to screening is something other than genetic testing, often because of low penetrance (e.g. hereditary hemochromatosis)

Pre-test considerations Most companies offer whole exome sequencing as the testing method This method improves sensitivity of testing across ethnicities Limited detection of some types of mutations Laboratories are likely to report variants which are classified as ‘likely’ pathogenic How will you counsel for a variant? Will your local genetics clinic provide support?

Post-test counselling and considerations Genetic counselling through testing company may be available +/- extra fee You (ordering provider) should have a plan to provide accurate information and follow up to patients, including: Risk counselling and review of options Test partner if one member of the couple is a carrier Additional testing e.g. biochemical testing for non-Ashkenazi Jewish (AJ) member of a couple where the AJ member is a carrier of Tay Sachs disease Significance of this information for other family members who may also be carriers

Back to Julie and Chris Julie and Chris are found to both be carriers of known pathogenic mutations in the cystic fibrosis gene, CFTR You refer the couple to your local genetics for follow-up counselling

Your local genetics centre Geneticseducation.ca > Genetics Centres

Expanded carrier testing supports patient autonomy and may help some couples avoid long wait times for genetics consults Physicians ordering testing need to be informed about the conditions on the panels and prepared to provide both pre- and post-test counselling Currently expanded carrier screening is not standard of care Pearls

Resources Genetics Education Canada – Knowledge Organization Edwards JG, Feldman G, Goldberg J, et al. Expanded carrier screening in reproductive medicine-points to consider: a joint statement of the American College of Medical Genetics and Genomics, American College of Obstetricians and Gynecologists, National Society of Genetic Counselors, Perinatal Quality Foundation, and Society for Maternal-Fetal Medicine. Obstet Gynecol 2015;125(3): Henneman L, Borry P, Chokoshvili D, et al. Responsible implementation of expanded carrier screening. Eur J Hum Genet [Epub ahead of print] Society of Obstetricians and Gynaecologist of Canada (SOGC)