Thursday September 28, 2017

GC-103 – DNA-direct: A trial of a new approach to genetic service delivery

BEDARD, Angela C, NUK, Jennifer E, LAWRENCE, Chalaine, SUN, Sophie, SCHRADER, Kasmintan A

Affiliations: BC Cancer Agency, Abbotsford

Introduction: Cancer genetics services for the population of BC and Yukon are provided by the BC Cancer Agency’s Hereditary Cancer Program (HCP). With increasing demand for cancer genetics services, there has been a resultant increase in the HCP’s wait list. The program has given consideration to alternate modes of service delivery in order to alleviate wait times for patients. One of these alternatives is providing an abbreviated pre-test telephone appointment to expedite the testing process. This method has been trialled successfully in the Netherlands, and was termed DNA-direct. In April 2017 the HCP began to trial the DNA-direct approach.
Methodology: The process used by the Dutch group was adapted, with permission, for use by the HCP. The process included triage of eligible patients, a brief telephone appointment, and mailing a post-appointment testing package. The criteria for patient inclusion were geographic location (patient lived outside of driving distance from HCP clinic), eligibility for index genetic testing not pending review of family medical records, and fluency in English. A ratio of 5 DNA-direct appointments were scheduled in lieu of 2 traditional pre-test appointments. The telephone appointment included reviewing reason for referral, updating pertinent family history, targeted questions for relevant history not included in medical record, abbreviated psychosocial assessment, and review of genetic testing process. A post-appointment testing package mailed to the patient included a cover letter, test requisition, consent form, and patient education fact sheet. The time spent for case preparation, appointment, and follow up were tracked for each case. Once results are received, all patients will be scheduled for a typical results disclosure appointment.
Results: Over a 6-week time span, 31 patients had a DNA-direct appointment. There was a 94% acceptance rate for the appointment type. The average time spent was 5 minutes for case preparation, 14 minutes for the appointment, and 11 minutes for follow up. The indications for testing included query hereditary breast and ovarian cancer syndrome, MLH1 promoter hyper-methylation screening, and colorectal polyposis syndromes. Return of results will range from 1 – 3 months from the initial appointment. All patients consented to re-contact for quality assurance and research. After results are delivered, the MICRA questionnaire will be administered, to compare coping and adaptation to test results between those who had DNA-direct appointments vs. traditional appointments.
Conclusion: The DNA-direct approach has demonstrated significant efficiencies with respect to pre-test genetic testing appointments. Patient satisfaction and distress levels will be gauged before considering broader adaptation of the process. This approach may be one of several to help address extended wait times in our field.


Thursday September 28, 2017

GC-108 – Patient outcomes of genetic counselling: assessing the impact of different approaches to family history collection

SLOMP Caitlin, MORRIS Emily, INGLIS Angela, LEHMAN Anna, AUSTIN Jehannine

Affiliations: University of British Columbia, Vancouver

Background: Documentation of family history (Fhx) is fundamental to the practice of genetic counselling (GC). Various approaches for obtaining Fhx have been employed, often motivated by a desire to increase efficiency. However, no studies have evaluated whether different modalities for collection of Fhx data influence patient outcomes. Pre-appointment phone calls have the theoretical advantages of: a) helping to clarify expectations and initiate rapport building, and b) allowing the patient and counsellor to more fully attend to the content of the GC session.
Objectives: We sought to test the hypothesis that more dramatic improvements in patient outcomes (specifically, empowerment and self-efficacy) of psychiatric GC would occur when Fhx was collected via telephone prior to the appointment (FhxPrior) as compared to when Fhx was collected during the appointment (FhxDuring).
Methods: We used data from our specialist psychiatric GC clinic, where as routine clinical practice, patients complete the GC Outcomes Scale (GCOS, measuring empowerment) and Illness Management Self-Efficacy Scale (IMSES) immediately prior to the appointment (T1) and at one-month follow-up (T2), and timing/method of Fhx documentation is recorded. Standard practice for the clinic is to collect Fhx by phone prior to the appointment, but a proportion of Fhx are collected during the appointment (e.g. when a patient cannot be reached in advance). Study inclusion criteria required: 1) that clinical care (including T2 follow up) was completed between 1 February 2012 and 31 January 2017, 2) that Fhx was obtained from the patient him/herself, and 3) that the psychiatric GC appointment was conducted in person (rather than by telephone or videoconference). To test differences in patient outcomes between groups, we conducted one-way between-groups analyses of covariance (ANCOVAs) on T2 GCOS and IMSES scores using baseline T1 scores as the covariate.
Results: Complete data were available for 240 patients and were used for analysis (FhxPrior, n=206; FhxDuring, n=34). There was no difference in T2 GCOS scores between groups after controlling for T1 scores (p=0.412, d=0.12), but T2 IMSES scores were significantly higher for FhxPrior than FhxDuring after controlling for T1 scores (p=0.011, d=0.44). GCOS and IMSES scores increased significantly from T1-T2 for patients overall (p<0.0005, d=1.2 and p=0.004, d=0.25 respectively).

Conclusion: Our data support previous findings regarding the important positive outcomes of psychiatric GC for patients, and suggest that obtaining Fhx via telephone prior to a psychiatric GC appointment may lead to greater increases in patient self-efficacy as compared to obtaining Fhx during the GC appointment.


Thursday September 28, 2017

CG-110 – Exploring the influence of prenatal aneuploidy screening on maternal-fetal bonding: Development of a theoretical model

HIPPMAN, Catriona; AUSTIN, Jehannine

Affiliations:University of British Columbia, Vancouver, B.C., Canada

Background: The maternal-fetal bond (MFB) is the affectionate relationship between mother and fetus that precedes the development of the maternal-infant bond, which is crucial to child social and cognitive development. Given rapid technological advances in prenatal aneuploidy screening (PAS), emerging evidence that– regardless of result– it may have a negative impact on MFB suggests an urgent need to improve our understanding of the impact of PAS on MFB.
Objective: To explore the impact of PAS on MFB.
Methods: Pregnant women (26-34wks) who had made a decision about PAS were recruited from healthcare providers’ offices and community events to participate in semi-structured (45-60 minute) interviews. Data analysis informed data collection using the constant comparative method. Interviews were recorded and transcribed verbatim. Constructivist grounded theory was used in data coding to generate categories and a cohesive theoretical model. Reflexive journaling and peer debriefing were used to enhance credibility, confirmability, and dependability of results.
Results and Conclusion: Interviews were conducted until saturation was reached (N=27; chose PAS, -ve result-13, chose PAS, +ve result-3, no PAS-11). Overall, MFB development evolved in four parallel domains: physical, emotional, cognitive, and spiritual. MFB ‘activities’ in each domain interacted with other domains to strengthen or weaken MFB. Women who chose PAS, in particular those who planned to terminate in the event of a diagnosis, experienced a ‘pause in the pregnancy’– actively resisting MFB development in the cognitive domain to put the brakes on overall MFB development. After receiving reassuring results, there was a delay (~1wk) before women were able to re-connect with the MFB. This negative impact on the MFB appears transient; women who chose PAS were as likely to achieve a strong MFB in the 3rd trimester as women who chose not to have PAS. Our findings provide insight into patients’ experiences that can enhance clinicians’ ability to empathize with patients as they engage in PAS choices and outcomes.


Thursday September 28, 2017

GC-141 Analysis of PGD Outcomes at Olive Fertility Centre Inc.

BUTLER Rachel, GUIMOND Colleen, LEE Nora, JING Chen, YUZPE Albert

Affiliations: Olive Fertility Centre Inc. Vancouver, BC

Introduction: Pre-implantation Genetic Diagnosis (PGD) has been offered as a service at Olive Fertility Centre (OFC) since the clinic’s inception in February 2013. Patients are guided through the PGD protocol by a multidisciplinary team including a reproductive endocrinologist, a nurse coordinator, a genetic counsellor, as well as a member of the finance department. The medical and genetic portion of the counselling process is, in itself, complex but is further confounded by the financial aspect since IVF is not covered by the BC Provincial Health Insurance Plan. Before committing to treatment, patients want to know the chances of obtaining a pregnancy given their age, as well as genetic and fertility history. To this end, outcomes from OFC’s PGD patient population were compiled to give patients a better understanding of our success rates.
Materials & Methods: Each couple undertaking PGD undergoes an IVF cycle. Embryos are grown to the blastocyst stage and tested sequentially, first for aneuploidy by means of NGS and then for PGD by karyomapping. Patient data including the PGD/CCS results are entered in an electronic medical records system (eIVF). Data was mined to extract patient demographics, genetic history, IVF cycle information, embryo number, PGD testing results and outcomes.
Results: To date, 65 patients have completed 101 IVF/PGD cycles resulting in the formation of 364 blastocysts.
Single Gene PGD: Forty-three (66.2%) patients had a single gene disorder. Twelve (27.9%) patients did more than one IVF cycle. A total of 240 blastocysts were tested. Seven patients had no blastocysts to test, 4 had only aneuploid embryos, 4 had euploid embryos that were affected with the mutation, 4 had euploid carrier embryos and 24 (55.8%) had euploid, unaffected embryos. For the 26 patients that transferred euploid carrier or unaffected embryos, the pregnancy rate per transfer was 81.1%, with 70% of these pregnancies ongoing. The cumulative pregnancy rate for patients who had an embryo transfer was 92% with 83.3% of these patients currently pregnant or delivered.
Chromosome Rearrangement PGD: Twenty-two (33.8%) patients had chromosome rearrangements, with translocations accounting for 72.7% of cases. Eleven (50%) patients did more than one IVF cycle. Of the 124 blastocysts tested, 36.2% were euploid (normal or balanced). Fourteen patients had at least one euploid embryo. For the 10 patients that transferred a normal or balanced embryo, the pregnancy rate was 50.0% per transfer, with 66.7% of these pregnancies ongoing. The cumulative pregnancy rate for patients who had an embryo transfer was 70% with 85.7% of these patients currently pregnant or delivered.
Conclusions: A review of the demographics and outcomes of the PGD program at Olive Fertility are summarized. This information can be used in counselling new clients in terms of expectations of success following PGD cycles at our Centre.


Thursday September 28, 2017

GC-142 What to expect when she’s expecting: The development of multidisciplinary obstetrical and neonatal management guidelines for Long QT Syndrome types 1 and 2 in British Columbia

MCINTOSH Sarah1, HATHAWAY Julie, GREWAL Jasmine, RYCHEL Valerie, BOS Hayley, SHERWIN Elizabeth, KRAHN Andrew, ARBOUR Laura

Affiliations: 1Dept of Medical Genetics, University of British Columbia; BC Inherited Arrhythmia Program

Background: Although the majority of women with Long QT syndrome (LQTS) types 1 or 2 have uneventful pregnancies, extra monitoring of the mother, fetus and newborn from conception to the postpartum period is warranted to prevent adverse outcomes. Maternal issues include choice and titration of beta-blocker and monitoring for cardiac events, especially in the higher risk postpartum period. Fetal growth surveillance is required due to the association between beta-blockers and intrauterine growth restriction (IUGR). The newborn must be followed carefully due to the possibility of adverse effects of beta-blocker exposure in utero or through breast milk.
To date, no comprehensive guidelines exist to guide clinicians on best practices for obstetrical and postpartum management of LQTS. Frequent clinical dilemmas prompted the BC Inherited Arrhythmia Program to form an expert group to develop Provincial consensus guidelines. The expert team, comprised of an obstetrician and cardiologist from a high-risk cardiac obstetric clinic, pediatric and adult electrophysiologists, geneticists, and a perinatologist are holding ongoing meetings to review the literature, build consensus, and invite input from primary care providers.
Recommendations: These consensus guidelines, currently in development, will provide specific expert-level recommendations including:
• Titrate beta-blocker up through the latter stages of pregnancy due to increasing blood volume and excretion, and back down to pre-pregnancy levels in the postpartum period
• During labour, anaesthesia, and delivery: avoid potential triggers for ventricular arrhythmia such as QT-prolonging medications, electrolyte imbalance, excessive bleeding and prolonged 2nd stage pushing
• Monitor fetal growth by ultrasound at 18, 28 and 36 weeks, with follow-up scan in two weeks and referral to obstetrician if any growth concerns identified
• Monitor for signs of beta-blockade (drowsiness, hypotension, bradycardia, and hypoglycemia) in the newborn and breastfeeding infant
• Perform ECGs on day 1 and 3 weeks of life
• Discuss genetic testing for LQTS (if known mutation in family)
Conclusion: The development of multidisciplinary obstetrical and neonatal management guidelines for LQTS types 1 and 2 will provide a foundation for further national and international practice guidelines. Evaluation from patient and provider perspectives will determine next steps.


Thursday September 28, 2017

GC-148 The gynecology-oncology BRCA (GO-BRCA) Pilot Project: Oncologist-mediated genetic testing of the BRCA1/2 genes for women with ovarian cancer.

DESMARAIS Stephanie1, KOHUT Ruth, PERRIER Renee, GLAZE Sarah, and SWEENEY Pam

Affiliations: 1Hereditary Cancer Clinic, Alberta Children’s Hospital, Calgary

Objectives: To ensure women with epithelial ovarian cancer in Southern Alberta have timely, seamless access to BRCA1/2 testing, while preserving informed choice and genetic counselling support in disclosing results. GO-BRCA was driven by a need to challenge existing care models, given a doubling of referrals to the Hereditary Cancer Clinic (HCC), due to the “Jolie effect”. Access to timely genetic testing is vital, as treatment may depend on BRCA1/2 status.
Methods: BRCA1/2 testing was historically offered after a pre-test genetic counselling session at the HCC. During GO-BRCA, (2016-01-25 to 2017-03-31), pre-test genetic counselling was facilitated by the gynecology-oncology (GO) team, in parallel with a referral to the HCC. The HCC disclosed results and provided post-test genetic counselling. GO-BRCA was a proof-of concept pilot, modeled after the UK Mainstreaming Cancer Genetics Program.
The GO team was oriented to pre-test genetic counselling by the HCC’s geneticist team lead. Support materials included key discussion points, BRCA1/2 test ordering instructions, and frequently asked questions. For patients, the GO team was given a brochure, a 2-page personal/family history form, and, a 5-minute video, to facilitate informed consent. Members of each team shadowed the other’s clinics to better understand clinic flow and logistical issues.
To evaluate acceptability of, and satisfaction with, GO-BRCA, qualitative surveys were issued to the GO team at the outset and close of the pilot, and to patients at the time of testing and at results disclosure.
Results: 121 women opted for BRCA1/2 testing during GO-BRCA; 85 results are complete to date. Time from HCC referral to results disclosure for women with ovarian cancer pre-GO-BRCA (June 2013-December 2015) compared to the GO-BRCA cohort was, on average, 309 days (median 275 days), versus 162 days (median 142 days). By eliminating pre-test meetings with the HCC, results were returned to patients 52% faster. Capacity of the HCC to see patients for other indications was increased by 121 hours. Of 59 women who returned pre-test surveys, 97% felt they made an informed choice about genetic testing, and 93% felt the GO-BRCA process worked well. Of 32 women who returned post-test surveys, 97% were happy they had testing, and 100% reported expectations were met, and were happy testing was offered by the GO team, versus at a separate HCC appointment. The GO team felt it was a feasible model to provide genetic services, provided they had adequate education and support from the HCC.
Conclusion: GO-BRCA provided BRCA1/2 genetic test results to women with ovarian cancer 52% faster than the usual model, and is accepted by patients and the GO-team. Elimination of pre-test meetings for ovarian cancer patients increased the HCC’s capacity by 121 hours. This model will become the provincial standard for ovarian cancer. Expansion to other oncology specialists is anticipated.


Friday September 29, 2017

GC-104 – Behavioural changes after psychiatric genetic counseling: an exploratory study

INGLIS, Angela1,2, HUYNH, Stephanie1, MORRIS, Emily1,2, AUSTIN, Jehannine1,2

Affiliations: 1Department of Medical Genetics, University of British Columbia, Vancouver, Canada

2Department of Psychiatry, University of British Columbia, Vancouver, Canada

Background: There is currently limited data relating to the effect of genetic counseling (rather than information) on patients’ health behaviors. With its focus on strategies to protect mental health, psychiatric genetic counseling (PGC) is conceptually positioned to produce health behavior changes. Indeed, research shows that PGC leads to increased patient empowerment and self-efficacy – both of which are necessary for patients to engage in behavior change. No studies have yet examined if PGC can evoke patient health behavior changes.
Methods: we conducted semi-structured interviews with eight patients with a personal history of psychiatric illness who had received PGC in Vancouver, Canada within the previous year, to explore its effect on health behaviors. Interviews focused on (i) experience with PGC services, (ii) perception of the etiology of mental illness and risk of developing symptoms, (iii) views on their past and current behavior and ability to change, and (iv) changes in their behavior since their PGC session. Guided by grounded theory, we used a constant comparative approach to data analysis.
Results: Participants reported increases in use of protective behaviors such as exercise, improving sleep habits, adhering to prescribed medication, seeking professional help and engaging in self-care. Participants reported increased sense of control, confidence and acceptance of their psychiatric disorder after PGC. This arose from having their feelings of guilt, shame, fear and hopelessness, and misconceptions and/or uncertainties about the etiology of psychiatric disorders and recommended risk-reducing behaviors addressed. PGC reframed participants’ initial perception of mental illness by separating cause into controllable and uncontrollable factors, discussing strategies to address the controllable factors and reiterating that everyone has a varying degree of susceptibility –some may be higher than others- but symptoms of mental illness are not predetermined.
Conclusion: Overall, participants reported health behavior changes and improved mental health outcome after PGC. Future studies could explore these changes quantitatively.


Friday September 29, 2017

GC-114 – Who are the cardiologists early to adopt integration of genetic counselors into clinical practice?


Affiliations: Stanford Center for Inherited Cardiovascular Disease, Stanford

Introduction: Genetic counselors (GCs) are increasingly involved in cardiology, as practice guidelines now recommend genetic counseling for individuals with inherited heart diseases. The 2016 NSGC Professional Status Survey indicates 10% of clinical GCs counsel patients in cardiology. Little is known about cardiologists who have integrated GCs into their practices.
Aim: To characterize cardiologists who have been early-adopters of integrating genetic counselors into their clinical services and explore their experiences with GCs.
Methods: We used a mixed methods design with a one-time online survey followed by telephone interviews with a subset of participants. Using the NSGC cardiovascular special interest group and our professional networks, we recruited cardiologists who care for patients with inherited heart disease and/or work with GCs. Survey questions covered physician demographics and how GCs fit into their practice. Survey results were used to inform purposive sampling for interviews; we selected cardiologists who work most closely with GCs, and aimed for a mix of adult and pediatric cardiologists from a variety of institutions and cardiac subspecialties. Interview data was transcribed and analyzed using elements of grounded theory.
Results: Eighty-five cardiologists completed the survey. The majority reported at least some of their patients are seen by a GC without involvement of a geneticist (85.9%). Of those, most had a GC in their cardiology department (74.6%, for a mean of 6.4 years, mean of 1.6 GCs per department). Nearly all reported the GC they work with is specialized in cardiovascular genetics (98.6%). Cardiologists who work with a GC predominantly work in an academic hospital setting (97.2%), and most early-adopters perform research (91.7% with 62.1% specifically researching genetics). Many staff a clinic dedicated to inherited heart disease (67.1%) and a mean of 34.2% of their patients have inherited heart disease. Cardiologists who do genetics research have been working with a GC for almost twice as long (mean 8.3 years vs. mean 4.7 years, p=0.001), and have more GCs in their department (mean 1.3 vs. mean 1.9, p=0.01) compared to those who do not do genetics research. Interviewees highly value GCs, feel GC training is rigorous, and appreciate the cardiovascular expertise of the GC(s) they work with. Billing, reimbursement, and funding for GC services has been a significant challenge in integrating GCs into cardiology.
Conclusion: Cardiologists who involve genetic counselors in their patients’ care work in academic hospitals and, in most cases, have genetic counselors embedded in their cardiology department. Those who do genetics research are the earliest adopters and have more GCs in their department. These cardiologists value the role, training, and expertise of GCs.


Friday September 29, 2017

GC-117 – Targeted Genetic Screening in Familial Late Onset Alzheimer Disease

GUIMOND, Colleen, GREENWOOD, Talitha, DWOSH, Emily, VILARINO-GUELL, Carles, FARRER, Matthew, HSIUNG, Ging-Yuek Robin, SADOVNICK, A. Dessa

Background: Alzheimer disease (AD) is the most common form of dementia. Although single gene causes of AD have been identified in individuals with early onset disease (< age 65 at first symptoms), the vast majority of AD is thought to result from the multifactorial interaction of inherited risk factors and environmental influences, with advancing age playing the largest role in AD development.

Methodology: Here we present data from 11 well-documented families selected for late onset disease (>65 years at first symptoms) and a striking family history of dementia in keeping with an autosomal dominant pattern of inheritance. At least one individual from each family underwent targeted sequencing for a panel of 177 genes associated with neurological disease.

Results: DNA samples from 20 affected individuals with late onset AD from 11 families identified 17 rare, missense variants with a minor allele frequency below 1% from publically available databases. In addition, mutations with proven pathogencity for AD and Parkinson disease were identified in Presenilin 2 (PS2) and DNAJC13 genes, respectively. Two individuals were found to be heterozygous carriers of causative mutations for recessive neurological conditions including early onset parkinsonism and Wilson disease with mutations identified in PARK2 and ATP7B, respectively.

Conclusions: This study has two important findings. Firstly, identification of a previously reported pathogenic mutation in an established gene known to cause early onset AD is further evidence that PS2 may play a role in late-onset AD as well. This information may guide testing options available to families presenting with late onset familial forms of AD for whom limited testing is currently recommended. Secondly, the identification of numerous missense variants in biological pathways related to neurological functioning adds to our understanding of the complexity of AD development and lends credence to the underlying multifactorial model of disease development even in families with apparent dominant disease.


Friday September 29, 2017

GC-132 Cascade Recanting: The Impact of Variant Reclassification in a Provincial Cardiogenetics

BARTELS Kirsten1, HATHAWAY Julie1, BURNELL Lindsay2, WONG Eugene3, VIRANI Alice4, ARBOUR Laura2, KRAHN Andrew1

Affiliations: 1St. Paul’s Hospital

2Victoria General Hospital

3University of British Columbia

4BC Women and Children’s Hospital

Presenter Institution: BC Inherited Arrhythmia Program, St. Paul’s Hospital, Vancouver BC

Background: Rapidly evolving genomic technologies have resulted in an exponential increase in the availability of clinical testing and allele frequency data in population databases. While this has led to new insights into the complexity of human sequence variation, it has also raised important challenges with respect to variant interpretation. In 2015, the American College of Medical Genetics (ACMG) developed stringent criteria in an effort to improve and achieve consensus in variant interpretation. However, applying these criteria to previously reported variants has led to a surge in their reclassifications. Little is known about how often these occur and how they impact clinical care. We report on the frequency of laboratory initiated clinically relevant variant reclassifications in the BC Inherited Arrhythmia Program (BCIAP) and their resulting clinical implications. Methods: Retrospective chart review of all probands who underwent genetic testing prior to, or during, an evaluation in the BCIAP from April 2013 to June 2017 was conducted. Data on probands (and relevant relatives) including diagnosis, genetic testing offered, initial and updated variant interpretation and resulting change to diagnosis/management was collected. Results: A total of 510 diagnostic genetic tests were offered to probands seen in the BCIAP. Reclassifications predicted to impact diagnosis (variant of unknown clinical significance (VUS) to likely pathogenic (LP)/pathogenic (P) or vice versa) were reported in 12/510 (2.35%) tests for 11 different variants in 12 probands. In 6 cases, variants were reclassified from LP to VUS and the remainder from VUS to LP. Eight variants (73%) were in Long QT syndrome (LQTS) associated genes and 5 (63%) were downgraded from LP to VUS. Reclassifications changed medical management in 1/12 (8%) probands. Thirty-nine family members (38 living, 1 deceased) underwent relevant targeted testing; 21 (20 living, 54%) were tested for a variant that was downgraded from LP to VUS. For 86% (18/21) of these relatives, the variant was in a LQTS gene. Seven had their medical therapy ceased and diagnosis removed, 10 had a change in the cardiac screening frequency and 3 saw no change to their management. Conclusion: Clinically significant variant reclassifications initiated by the laboratory were reported in approximately 2% of proband tests. This is likely an underestimate, as clinical laboratories are not required to proactively provide variant interpretation updates. Additional work is needed to adequately capture the extent of variant reclassifications in our program. Thus far, reclassifications appeared to impact the medical management of a small minority of probands (8%) but resulted in a change in management for 44% of relatives. Further research is needed to expand on the impact, both medically and psychologically, that these reclassifications have on families.


Friday September 29, 2017

GC-149 Exploring the perceptions of female carriers of X-linked conditions on having carrier daughters

HEDGES Stephanie1,2, HEWSON Stacy2, MURPHY Jillian3, SHUMAN Cheryl1,2, AMBURGEY Kimberly4, TAVARES Sandra3, CHITAYAT David1,2,5, and MYLES-REID Diane1,5

Affiliations: 1Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

2Division of Clinical and Metabolic Genetics, Department of Pediatrics, The Hospital for Sick Children, Toronto, ON, Canada

3Fred A. Litwin Family Centre in Genetic Medicine, University Health Network, Toronto, ON, Canada

4Department of Neurology, The Hospital for Sick Children, Toronto, ON, Canada

5Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

Genetic counselling is recommended for carriers of X-linked conditions to provide information/education, to discuss recurrence risk and reproductive options, and to explore the utility of reproductive genetic testing. Previous research has been undertaken to explore the perceptions of carrier women regarding having a son with an X-linked condition, as well as the feelings of female carriers regarding carrier testing and reproductive planning. To date, a paucity of research exists exploring female carrier perspectives on having a carrier daughter, specifically regarding the use of prenatal diagnosis to determine carrier status in female pregnancies. Our study aimed to gain insight into the perspectives and emotions of women hemizygote for a pathogenic variant in specific X-linked conditions about transmitting the variant to daughters, prenatal carrier detection, and the reproductive testing options used to do so. Ten women, carriers of four different X-linked conditions, were recruited to participate in our qualitative study. Utilizing a semi-structured guide during telephone interviews, we reviewed participant’s family and reproductive history, and examined views on carrier testing as well as reproductive testing methodologies. Interview transcripts were analyzed via interpretive phenomenological analysis. All ten women support prenatal and preconception carrier testing. Four main motivational themes for this testing emerged from the data: 1) a concern for the daughter to develop symptoms of the condition, 2) the burden for child bearing, 3) a search for knowledge, 4) the desire to plan for the future. The results of our study support the growing literature surrounding the feelings of carrier females about their carrier status including themes of impact on self-identity and relationships, disruption of family planning and a feeling of responsibility. We identified four main barriers to reproductive testing – financial, proximity to services, risk aversion, and emotional burden. Altogether, our study demonstrates the desire for women in this population to have increased access to knowledge of the symptoms associated with carrier status, reproductive testing options, and supports within their communities – all areas that could be better incorporated within the role of the genetic counsellors serving this population.


Friday September 29, 2017

GC-150 Families want predictive genetic testing early in childhood for inherited arrhythmias and cardiomyopathies.


Affiliations: University of Alberta, Edmonton, AB

Background: Assessing the pros and cons of predictive genetic testing in minors is complex and involves consideration of several ethical principles along with the natural history of a disease. Predictive genetic testing is common in childhood for inherited arrhythmias and cardiomyopathies, however, there are mixed opinions regarding the optimal age to perform testing.
Study objective: The objective of this study was to evaluate when, in childhood, families believe that predictive genetic testing should be performed for children at risk for long QT syndrome (LQTS), hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). The study also assessed the importance families place on various ethical factors in determining when predictive genetic testing should be performed.
Method: Individuals over 18 years of age who have or have a partner with a genetic diagnosis of LQTS, HCM or ARVC were invited to complete an online survey. Respondents were asked to select the age that they felt predictive genetic testing should be performed and to rate on a scale of 1 to 5 the importance of 8 potential factors in the decision making process.
Result: In total 210 individuals responded to the survey. The vast majority (92%, 70/76) of families with a diagnosis of LQTS reported that predictive genetic testing should be performed before 5 years of age. In addition, 70% (94/134) of HCM and ARCV families felt that testing should be performed this early. The ethical factor that families rated as most important was beneficence which includes clarifying the need for cardiac screening (4.8/5), prescription of medication for individuals with a genetic diagnosis of LQTS (4.8/5), guiding sport participation (4.4/5), decreasing worry for those found not to carry the familial variant (4.2/5), and having time to adjust to the diagnosis (3.9/5). Non- maleficence was rated as less important with regard to impacting insurability (3.4/5) and creating anxiety for carriers (2.8/5). The least valued ethical principle was autonomy which involves allowing a child to take part in the decision making process (2.5/5).
Conclusion: Regardless of diagnosis, the majority of respondents reported that predictive genetic testing should be offered between 0 and 5 years of age. These findings support having a detailed discussion with the parents of young children at risk for LQTS, HCM and ARVC about the potential impacts of testing. This would allow them to make a personal decision around the timing of testing that is consistent with their family values.