Poster Presentations

Poster Session Objectives:

At the end of this session, participants will be able to:

  • Identify ongoing research around the country.
  • Communicate with colleagues from around the country.
  • Promote research collaboration.
  • Extend opportunities for members to discuss and examine research and clinical work in a supportive, collaborative environment.


THURSDAY SEPTEMBER 12 at 6:00-7:30 p.m.



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GC-101 Utilization of normal adjacent tissue for germline confirmation

JESSEN, Jaime, JACOB, Karine, DESAULNIER, Melissa, RACHER, Hilary

1Impact Genetics, Bowmanville, ON, Canada.


Background: Mismatch repair (MMR) somatic tumor variants found in reflex testing of normal DNA can confirm or rule out a diagnosis of Lynch Syndrome.

Objectives: In this discussion, we review a case from 1999 in which we were able to extract DNA from normal adjacent tissue (NAT) within the FFPE tumor sample slides and provide confirmation of an underlying MMR germline pathogenic variant consistent with Lynch Syndrome.

Design/Method: Immunohistochemistry was performed on this patient’s tumor sample which showed loss of MSH2 and MSH6 expression and absence of the V600E BRAF change; there was no loss of MLH1 or PMS2. Next-generation sequencing (NGS) and Multiplex Ligation-dependent Probe Amplification (MLPA) were performed on tumor and normal adjacent tissue DNA extracted from FFPE tissue for MLH1, MSH2, MSH6, PMS2 and EPCAM genes.

Results: MLPA identified two pathogenetic deletions of MSH2; del2->8 and c.1697delA (p.Asn566Ilefs*24) in tumor DNA. MLPA performed on DNA from NAT also identified the deletion of MSH2 del2->8 supporting that this patient has Lynch syndrome. This deletion was confirmed using two independent MLPA kits (MRC Holland P003-D1 and P248-B1).

Conclusions: This case illustrates the capability of confirming underlying Lynch syndrome by using DNA obtained from NAT present in FFPE tumor samples. This is a valuable tool when the proband is deceased and DNA obtained from blood is not available.

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GC-102 An interesting case of synchronous endometrial and ovarian carcinomas analyzed through mismatch repair somatic tumor genetic testing

JESSEN, Jaime1, RACHER, Hilary1, DESAULNIER, Melissa1, MATEVSKI, Donco1, DESMARAIS, Stephanie2, PERRIER, Renee2, JACOB, Karine1

1Impact Genetics, Bowmanville, ON, Canada.

2Alberta Children’s Hospital, Calgary, AB, Canada.


Background: The diagnosis of the simultaneous occurrence of adenocarcinoma of the uterus and the ovary remains challenging as they could represent two independent primary tumors or metastatic dissemination from one site to another.

Objectives: In this discussion, we review a case of synchronous endometrial and ovarian cancer in which the identification of the same MSH2 somatic variants in both tumor types showed evidence of clonal lineage.

Design/Method: Immunohistochemistry was performed on this patient’s ovarian (tumor A) and endometrial (tumor B) samples which showed loss of MSH2 and MSH6 expression, and intact nuclear expression of PMS2. Mismatch repair somatic tumor testing using next-generation sequencing was performed on both tumor samples for MSH2 and MSH6 genes.

Results: The same two MSH2 somatic, pathogenic nonsense variants (c.2034T>A (p.Tyr678Ter) and c.1216C>T (p.Arg406Ter)) were identified in the two tumors samples from this patient. Both variants were confirmed by Sanger sequencing in DNA from (tumor A) and in DNA from (tumor B) and were not detected in the patient’s extracted from DNA from blood, consistent with the previously reported negative MSH2 germline results.

Conclusions: In this patient, the identification of the same MSH2 somatic variants in both tumor types is suggestive of the presence of clonally related tumors. Given that neither MSH2 variant was detected in this patient’s blood reduces the likelihood that this patient has Lynch syndrome.

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GC-103 A challenging case of endometrial cancer low tumour cellularity: utility of alternative methods for variant confirmation

JESSEN, Jaime1, RACHER, Hilary1, PERRIER, Renee2, VAN GALEN Pauline2, DESMARIS, Stephanie2, BUCHNER Nicholas1, DESAULNIER, Melissa1, FRAYLING, Ian M.3

1Impact Genetics, Bowmanville, ON, Canada.

2Alberta Children’s Hospital, Calgary, AB, Canada.

3University Hospital of Wales, Cardiff, UK.


Background: Mismatch Repair (MMR) genetic testing to assess for somatic pathogenic variants in colorectal and endometrial tumour samples can explain the abnormal IHC and/or MSI tumour results in those patients with normal MMR germline (constitutional) testing.

Objectives: In this discussion, we review a challenging low tumour cellularity endometrial case with IHC MSH6 absent staining and normal MSH6 constitutional testing.

Design/Method: FFPE tumour and normal adjacent tissue DNA was extracted. Next-generation sequencing (NGS), sanger sequencing and allelic-specific PCR (AS-PCR) were performed for MSH6 coding regions. Variant classification was assessed using the criteria outlined by the International Society for Gastrointestinal Hereditary Tumours (InSiGHT).

Results: Two somatic variants were identified by NGS at a low mosaic level, each estimated to be present in 8% of the cells tested from this patients FFPE tissue block which was consistent with the predicted low tumour cellularity by pathology. Both variants were assessed by Sanger sequencing; however, only trace levels of both variants were detected above background signal. To confidently confirm or rule-out the NGS findings, unique AS-PCR assays were designed. AS-PCR confirmed the presence of both variants in the patients tumour sample as well as the absence of both variants in the patient’s DNA from blood, consistent with previously reported negative germline results

Conclusions: This case illustrates the challenges of low tumour cellularity in somatic tumour testing and the value of using alternative confirmation methods aside from conventional Sanger sequencing to provide confidence in variant calling.

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GC-104 Universal testing of endometrial cancer: Reaching an under-served population (UTERUS Project)

HAWRYSH, Andrea1, DAVIES, Kellie1, TREVORS, Christopher2, RACHER, Hilary2, JESSEN, Jaime2, JACKEL-CRAM, Candice1

1Division of Medical Genetics, Royal University Hospital, Saskatoon, SK.

2Impact Genetics -Dynacare, Bowmanville, ON, Canada.


Background: Mismatch Repair (MMR) somatic genetic testing can be used as a first-tier molecular genetic test to identify both Lynch and biallelic somatic MMR (“Lynch-Like”) patients” by utilizing paired tumor and germline analysis.

Objectives: We aim to present a prospective provincial study for recently diagnosed endometrial cancer patients using paired tumor and germline MMR somatic testing approach. The goal of which is to demonstrate improved ascertainment of at-risk women and timely access to genetic results.

Design/Method: Led by the Division of Medical Genetics at Royal University Hospital (RUH), the program Universal Testing of Endometrial Cancer: Reaching an Under-Served Population (UTERUS) will offer comprehensive paired MMR tumor and germline testing to all RUH patients recently diagnosed with endometrial cancer. All women with endometrial cancer who do not have MMR deficient tumors will be offered panel-based genetic testing. The program was made possible through a $100,000 grant from the Royal University Hospital Foundation’s Women Leading Philanthropy program.

Results: This project will serve all patients with endometrial cancer and hypothesis results are that this approach will lead increasing early detection, improving access to genetic testing for all communities, and ultimately improving patient outcomes by providing universal testing at the time of diagnosis.

Conclusions: The goal is to show this approach to genetic testing will improve timely access and uptake of genetic services, capture data on patient preferences and satisfaction with delivery of genetic services and increase understanding of the role of inherited cancer syndromes other than Lynch syndrome in the endometrial cancer population.

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GC-105 Hereditary cancer genetic testing within an unaffected adult patient cohort

LOHN Zoe1, FOK Alexandra2, RICHARSDON Matthew3, MUNG Sze Wing1, NUK Jennifer1, YUSON Jamie1, JEVON Mandy1, SCHRADER Kasmintan*1,4,5, SUN Sophie*1,6

1Hereditary Cancer Program, BC Cancer, Vancouver, B.C., Canada.

2Canada’s Michael Smith Genome Sciences Centre, BC Cancer, Vancouver, B.C., Canada.

3Department of Interdisciplinary Oncology, The University of British Columbia, Vancouver, B.C., Canada.

4Department of Molecular Oncology, The University of British Columbia, Vancouver, B.C., Canada.

5Department of Medical Genetics, The University of British Columbia, Vancouver, B.C., Canada.

6Division of Medical Oncology, The University of British Columbia, Vancouver, B.C., Canada.

*Equal contributions.


Hereditary cancer genetic testing provides information to aid in cancer prevention and early detection among individuals at high risk of cancer. However, regardless of family history, funding constraints within the public healthcare system have largely limited genetic testing in British Columbia (BC) to only individuals with a personal history of cancer. Funding was attained recently to offer testing to 400 patients previously deemed ineligible for testing. Eligible patients included unaffected adult individuals with a family history meeting provincial testing criteria where no testing has been performed in the family and there is no living testable relative in BC. Indications for referral included: hereditary breast and ovarian cancer syndrome (88%), Lynch syndrome (10%) and other syndrome (e.g. Li Fraumeni syndrome) (2%). Hereditary cancer panel testing was offered to patients (57 gene test which was then expanded to 61 gene test); variants of unknown significance were not reported. Overall uptake of testing was high (89%). Of the 299 patients who have completed testing, 5.3% (N=16) have had a pathogenic or likely pathogenic variant identified including: BRCA1 (2), BRCA2 (2), PALB2 (1), MLH1 (1), MSH2 (1), MSH6 (1), monoallelic MUTYH (2), MITF (1), FH (2), BRIP1 (1), NBN (1), TSC1 (1). Emerging data presented here documents the experience of hereditary cancer genetic testing within an unaffected patient population.

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GC-106 MMR Universal Screening of Endometrial cancers- The MUSE Project: Applications to clinical cancer genetic counselling

Lawrence J, Richer L, Arseneau J, Zeng Z, Chong G, Weber, E, Foulkes W, Palma L.


Universal screening of endometrial cancers by immunohistochemistry (IHC) was implemented in October, 2015 at the McGill University Health Centre to improve ascertainment of Lynch syndrome (LS) patients presenting with endometrial cancer and to assess the feasibility of a long-term IHC screening program. Between October 1, 2015 and December 31, 2017, 276 invasive endometrial cancers were screened for mismatch repair deficiency (MMR) as part of the general clinical work-up of endometrial cancer patients. Our study aim was to evaluate whether universal IHC screening of endometrial cancers more effectively identifies individuals with germline MMR gene mutations than traditional referral/clinical criteria. Secondary aims included evaluating the performance of our screening algorithm and identifying clinical predictors that may be used to identify endometrial cancer patients with/without germline MMR gene mutations.

We will present the outcomes of this study, including a brief overview of different screening protocols used to identify individuals with LS. We will review our screening algorithm and compare the performance of clinical-based ascertainment of LS patients to our universal screening approach, highlighting the pros/cons of each. Descriptive and quantitative summary statistics will be presented for the following: prevalence of MMR gene mutations among unselected women with endometrial cancer; total number of tumours screened to identify one MMR germline mutation; demographics and family histories of the women found to have LS by our screening protocol. Finally, we will discuss how this information may be relevant to the practices of clinical cancer genetic counselling and/or oncology clinics.

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GC-107 Double germline variants in different cancer predisposition genes: a laboratory summary of findings

LYON Elizabeth1, HRICIK Mary, NOETH Dagny, VICTORINE Anna, HAYDEN Melissa, WILLIS Alecia

1Laboratory Corporation of America, CMBP, Research Triangle Park, NC.


Background: The increasing use of hereditary cancer multi-gene panels has identified more individuals with pathogenic (PVs) or likely pathogenic variants (LPVs) in two or more genes.1 These patients are at increased risk for multiple primary cancers which may pose new management and treatment challenges. Currently, data on genotype-phenotype correlations and corresponding management guidelines are limited. The aim of this study is to describe a cohort of patients who were identified with two or more PVs/LPVs in cancer predisposition genes.

Methods: This study is a retrospective case review of 17 hereditary cancer orders that were identified to have two or more PVs/LPVs in different genes. Patients were tested on one of three hereditary cancer tests: BRCA1/2, a Lynch syndrome panel, or a comprehensive multi-gene cancer panel. Analyzed data included test results, variant classification, and reported personal cancer history.

Results: One patient, with a reported personal history of multiple cancers: breast, 59; colorectal, 65; and endometrial, 73, was identified to have two pathogenic variants: ATM c.3372C>G and MUTYH c.1187G>A. This was the only patient to have 3 different reported cancers. In the study, twenty-seven different variants in 13 unique genes were identified with MUTYH, BRCA2, and BRCA1 occurring most frequently. Three unique MUTYH variants were found in ten patients. Six unique BRCA2 and five BRCA1s variants were observed in 7 and 5 patients, respectively. Sixteen PVs and 11 LPVs were identified across the cohort. The majority of patients (6, 35%) had a personal history of breast cancer (mean age of diagnosis 61.3). Colorectal cancer (CRC) (17.6%) was the second most common cancer (3, mean age of diagnosis 48). Other personal histories of cancer included: ovarian (2, ages 46, 67), and gastric (1, age 34). Three patients reported no personal cancer history, one did not provide history, and two reported colon polyps. Two patients (11.8%) experienced cancer recurrences: one breast and one CRC. The average age at testing for patients with a cancer history was 41. Without a reported malignancy, the patients’ average at testing was 42.

Discussion: Clinical genetic testing laboratories are well positioned to identify patients harboring variants in multiple cancer predisposition genes. In this study, the average age of 41 years in the cohort suggests there is time for other early onset cancers to arise. The data suggest the need for additional long-term data collection, as the cohort age increases, to evaluate the need and timing of early screening and interventions. With continued collaboration between clinicians and laboratories, phenotypic correlations will better predict cancer risks and improve medical management for this population of patients.

1Whitworth J et al: Multilocus Inherited Neoplasia Alleles Syndrome. JAMA Oncology 2(3):373-379, 2016.

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GC-108 Utility of gene panel testing in children with seizure onset after 2 years of age: results from a European and Middle Eastern epilepsy genetic testing program


Blueprint Genetics, San Francisco.


Background: Epilepsy is one of the most common childhood-onset neurological conditions with a genetic basis. Genetic diagnosis provides potential for etiologically-based management and treatment. Existing research has focused on early-onset (<2 years) epilepsies while data regarding later-onset epilepsies is limited. Program goals: Determine, in a selected pediatric epilepsy cohort, the overall and actionable molecular diagnostic (MDx) yield and the CLN2 disease MDx yield. CLN2 is a severe, rapidly progressive neurodegenerative disease with onset of seizures at/after 2 years and average age-of-diagnosis of 5 years.

Methods: Blueprint Genetics’ next-generation sequencing (NGS)-based 283-gene epilepsy panel was used. Copy number variant (CNV) detection from NGS data was included. Variant interpretation was performed according to ACMG guidelines. Program results (Oct/2017-Nov/2018) are reported from 210 patients (Europe, Middle East) with inclusion criteria: Age 24-60 months, first seizure at/after 24 months, and at least one additional finding. The program was sponsored by BioMarin Pharmaceutical Inc.

Results: Median age-at-testing: 42 months; median age-of-first-seizure-onset: 30 months; average delay from first seizure to comprehensive genetic testing: 10.3 months. Genetic diagnosis was established in 42 patients; 20.0% MDx yield.?CNVs were reported in 26.2% of diagnosed patients; 27.3% of CNVs identified were intragenic. MDx included 5 CLN2 (TPP1 gene) diagnoses, 4 MECP2, 3 SCN1A, 3 Angelman syndrome, 2 each of CHD2, KCNA2, MFSD8, SCN2A and STXBP1.

Conclusion: This program demonstrates the clinical utility of a comprehensive epilepsy gene panel for patients with first seizures at/after 2 years for MDx of pediatric epilepsy and CLN2 disease to guide management and treatment.

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GC-109 Ethnicity and carrier testing for hereditary cancer in British Columbia

BRALEY, Eryn1, BEDARD, Angela2, BEDARD, James1, HONG, Quan2, NUK, Jennifer2, SCHRADER, Kasmintan2, SUN, Sophie2

1University of the Fraser Valley, Abbotsford, BC.

2BC Cancer Hereditary Cancer Program.


Introduction: Carrier testing for hereditary cancer is highly accurate and cost-effective for identifying individuals at high risk for cancer; however, not all eligible people utilize the service. While sociodemographic factors related to the uptake of carrier testing, such as age and gender, have been fairly well described in the literature, there is a paucity of data available about the role of ethnicity. BC Cancer’s Hereditary Cancer Program (HCP) has been systematically collecting ethnicity data since 2015, allowing for a four-year cascade carrier testing analysis for this factor.

Methods: The HCP’s program database was queried for index tests and corresponding carrier tests of their relatives facilitated between February 3, 2015 and March 7, 2019. Factors examined included ethnicity, gender, age, postal code, referral source, genes tested, and cancer diagnoses. Descriptive statistics were computed; mean and standard deviation is reported for continuous variables and proportion is reported for categorical variables. Patient ethnicity was classified according to the Canadian Census ethnicity classifications and compared to the 2016 BC Census data.

Results: There was significant variability in the uptake of carrier testing in the three largest population groups (p < 0.01), with individuals of European ethnic origin overrepresented (12% higher than general population), individuals of Asian ethnic origin modestly underrepresented (16% lower than general population), and individuals of North American Aboriginal origin considerably underrepresented (60% lower than general population). Individuals reporting other ethnic origins, which make up the smallest proportion of BC residents (African, Caribbean, Oceanian, and Latin, Central and South American) had variable uptake of testing. 1.3 carriers per index case received carrier testing during the study period. The majority of carrier tests were for BRCA 1/BRCA2 (58.8%), followed by 16.9% for Lynch Syndrome genes. 70% of those receiving carrier tests were female and 30% were male. The mean age of individuals seeking carrier testing was 49.4 (SD = 17.6).

Discussion: This study provides initial insight into uptake of carrier testing by patient ethnicity. Additional analyses planned for the short term include comparing the number of relatives having carrier testing by index patient ethnicity, and the amount of time to testing. Examining patient ethnicity and genetic testing helps identify underserved populations. Our analysis highlights underrepresentation of Indigenous individuals for hereditary cancer carrier testing, which parallels the results of other cancer screening studies. This research may help to promote awareness of underrepresentation of Indigenous populations for genetic testing, and the development of better alternatives to outreach and service promotion.

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GC-110 Prenatal Genetic Counselling for Megacystic Microcolon Intestinal Hypoperistalsis Syndrome (MMIHS): A Clinically Variable Condition

MILLER, Kristen, NEZARATI, Marjan, MEI-DAN, Elad

North York General Hospital, Toronto, Ontario.


Introduction: Megacystic Microcolon Intestinal Hypoperistalsis Syndrome (MMIHS) is a rare condition with over 200 cases reported in the medical literature. MMIHS is associated with autosomal dominant pathogenic variants in ACTG2, MYH11, and LMOD1, and MYLK. ACTG2 encodes the gamma-2 actin protein which is important for muscle contraction and cell movement. Symptoms can range from severe neonatal megacystis to mild recurrent urinary tract infections in affected individuals. There is a much higher incidence of this condition in females than males, with a ratio of 4:1. Penetrance of ACTG2-related disorders is typically complete; however, the phenotype can present with variable expressivity. The degree of variability can complicate patient understanding and the associated genetic counselling.

Case: A case study was performed for a 38 year old in two subsequent pregnancies. In her first pregnancy, ultrasound at 19 weeks gestation identified a female fetus with a cystic structure in the fetal pelvis, and no separate bladder seen. Further ultrasound confirmed megacystis, consistent with a clinical diagnosis of MMIHS. Amniocentesis was performed and a maternally inherited, likely pathogenic mutation in the ACTG2 gene was identified. A discussion about the variability in presentation of ACTG2 mutations ensued. The patient returned in a subsequent pregnancy; amniocentesis was declined, and she opted to monitor through ultrasound, and no genetic testing was organized. No megacystis was identified. Labour was lengthy and the patient did not dilate more than 4cm. Caesarean section was organized. The patient had post-partum hemorrhage, and even after transfusion, subtotal hysterectomy was required.

The patient noted a history of constipation as a child, occasional bloating, and prolonged labour during genetic termination. Based on this history, we suspect that the likely pathogenic ACTG2 mutation may have contributed to the complications in both pregnancies.

Conclusions: This case illustrates the importance of genetic counselling to a patient’s understanding of complex diseases. Variable presentation is a difficult concept for patients to understand, and genetic counselling ensured the patient fully recognized the impact of these results for her and her pregnancies. The mild GI symptoms the patient experienced prior to pregnancy may be attributable to the ACTG2 variant, but were not significant enough to raise any concerns. However, the prolonged labour in her first pregnancy in combination with the ACTG2 variant made her health care providers aware of potential complications in her second pregnancy, and their timely intervention likely saved her life.

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GC-111 Enhancing the genetic counselling curriculum in medical genetics resident training

GOLDSMITH Claire, HONEYWELL Christina, CLOUTIER Mireille, CASTLE Alison, ZAMBONIN Jessica, LAZIER Joanna

Department of Genetics, CHEO, Ottawa.


Residents in the Royal College Medical Genetics and Genomics training program in Ottawa expressed a desire for an improved genetic counselling curriculum. A team of interested genetic counsellors, residents and the Program Director was formed to address this need.

Objectives: To better comprehend the roles of genetic counsellors in residency medical education, and use this knowledge to build a curriculum which allows a more complete understanding of the skills of a genetic counsellor, fosters positive career long relationships between geneticists and genetic counsellors and improves Medical Genetics residents’ counselling skills.

Methodology: We undertook an inventory of existing educational opportunities that are provided by genetic counsellors. These included didactic presentations as well as structured rotations. New and innovative teaching methods were considered, as were opportunities for teaching the professional and collaborative skills needed to work with genetic counsellors as a staff geneticist. We referenced the Objectives of Training in the Specialty of Medical Genetics and Genomics of the Royal College of Physicians and Surgeons of Canada to ensure that we aligned the new curriculum with the training objectives for our residents. By way of comparison, we also consulted both the Practice Based Competencies as well as the Knowledge-Based Competencies for Canadian Genetic Counsellors. We solicited information about similar educational opportunities for resident learners from other centres across Canada. We sought to be explicit about the expectations at each stage of training as well as the opportunities and methods for evaluation.

Results: It became apparent that there are a myriad of genetic counsellor-led learning opportunities available for the residents. This process led to the development of a structured, longitudinal genetic counselling curriculum for Medical Genetics residents extending over the three years of core genetics training. New opportunities were created which maximized resident education using existing genetic counsellor resources, and additional opportunities for informal interactions and mentoring.

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GC-112 Genetic counsellors’ comfort level and practices in discussing clinical trials for ocular genetic disorders with patients

ALEXANDRE Jennyphane1, BARET Laurence2, FITZPATRICK Jennifer1

1Department of Human Genetics, McGill University, Montreal, Canada.

2Division of Medical Genetics, Department of Medicine, McGill University Health Centre, Montreal, Canada.


Genetic counsellors support patient decision-making by providing information regarding genetic conditions as well as their testing, management and treatment options. Recently, there have been an increased number of clinical trials for ocular genetic conditions and an increased number of referrals to genetics clinics for patients diagnosed with inherited eye conditions for genetic testing and counselling. While previous studies have focused on the challenges faced by a variety of professionals when discussing clinical trials with patients diagnosed with cancer, no study has looked at the challenges faced explicitly by genetic counsellors when discussing clinical trials, whether for cancer or other conditions.

We sent a survey through the National Society of Genetic Counselors (NSGC) and the Canadian Association of Genetic Counsellors (CAGC) e-mail lists to ocular genetic counsellors to assess their current practices and comfort level when discussing on-going research and possible clinical trial participation with patients.

The majority of the respondents reported discussing clinical trials with their patients and that the majority of the time the patient will inquire about potential enrollment in a clinical trial during the genetic counselling sessions. However, the respondents who considered themselves to be specialized were more likely to feel comfortable discussing clinical trials with their patients than those who considered themselves to be non-specialized. One possible explanation is that specialized ocular genetic counsellors were also most likely to access resources to stay updated about clinical trials, which could increase their comfort with discussing the subject with their patients.

This study also suggests that there is a need among patients to have more information on clinical trials and that genetic counsellors can have an important role in filling in this educational gap. Finally, the majority of the respondents, specialized or non-specialized, reported feeling comfortable or very comfortable providing emotional support to patients when discussing clinical trials. This highlights the role the genetic counsellor can play in addressing the unique psychosocial issues that may arise when discussing clinical trials in the context of untreatable hereditary ocular conditions.

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GC-113 An exploration of genetic counsellors’ experiences with communicating data sharing concepts

SELVANAYAGAM Thanuja1,2, HAYEEMS Robin3,4, WALKER Susan5,6, CHITAYAT David1,7, BABUL-HIRJI Riyana1,2, LISTON Eriskay1,2

1Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, UofT, Toronto, ON.

2Department of Molecular Genetics, UofT.

3Child Health Evaluative Sciences Program, Hospital for Sick Children Research Institute, UofT.

4Institute of Health Policy Management and Evaluation, UofT.

5Program in Genetics and Genome Biology, The Hospital for Sick Children, UofT.

6The Centre for Applied Genomics, The Hospital for Sick Children, UofT.

7The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, UofT.


Data sharing is important for advancing genomic research and accelerating discoveries through the release of genetic and phenotypic information to online databases and/or researchers. However, there can be privacy risks to individuals. Evidence suggests that research participants have limited understanding of data sharing concepts and the complexity of data sharing choices may confuse and impact their ability to appreciate the associated benefits and risks. Genetic counsellors play a central role in the informed consent process for genomic research, but there remains a paucity of literature addressing genetic counsellors’ experiences with data sharing discussions and associated content in consent forms. This study aims to (i) explore the experiences and challenges that genetic counsellors face when discussing data sharing options with patients or research participants and (ii) describe the content, structure, and readability of data sharing concepts contained within genomic research consent documents. Through a survey that was delivered by email to principal investigators of Canadian genomic research studies, CAGC, NSGC and local Toronto genetic counsellor listervs, we recruited clinical and research genetic counsellors involved in genomic research. Semi-structured interviews were conducted, which were audiotaped, transcribed, and analyzed thematically. Genomic research study consent forms were collected and content analysis was conducted to describe similarities and differences in data sharing concepts and options. Of 18 eligible participants, 15 (83%) completed interviews and a total of 13 consent forms were obtained. Preliminary analyses show the most common data sharing options presented to patients include sharing to databases (e.g. Phenotips, MatchMaker Exchange), and researchers. Further, the discussion surrounding data sharing in counselling sessions is generally short, secondary to other topics and is typically guided by the language contained within the consent form. In addition, genetic counsellors have varying levels of confidence when discussing this topic and some find the uncertainty regarding how the data will be used in the future challenging to address. Lastly, patients’ understanding was generally not actively evaluated but rather gauged by their body language and the questions they asked. Content analysis of consent forms show heterogeneity within the length and the types of data sharing options that are outlined. Overall, our findings indicate that genetic counsellors have varied confidence in discussing data sharing and research consent forms vary widely with regards to data sharing content. The development of guidelines for standardized consent forms for genomic research and resources can help aid in facilitating conversations surrounding data sharing.

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GC-115 Description of the genetic assistant workforce in North America

KRUTISH Angela1, CHIN Shannon2, LIU Xiao-Qing1, HARTLEY Jessica N1

1University of Manitoba, Winnipeg.

2Shared Health Program of Genetics and Metabolism, Winnipeg.


Due to the shortage of genetic counsellors, clinics and laboratories have developed strategies to improve service delivery. Integration of genetic assistants is an example of one such strategy. Genetic assistants (GAs) are non-clerical staff who perform many of the “behind-the-scenes” coordination and administrative tasks otherwise assigned to a genetic counsellor. To date, there is only one published study about GAs. Although the research provided a good introduction to the GA position, it was limited to two centres and focused on GAs working in cancer genetics. Due to the sparsity of published data, we proposed a study of the GA workforce across North America. The objectives of this study were to: 1) describe the personal and position demographics, roles, and training of GAs and 2) estimate the number of individuals currently employed as GAs in Canada and the US.

We included two groups in the study sample: 1) GAs who worked in a genetics clinic or laboratory and 2) genetic counsellors, medical genetics residents, clinical geneticists, molecular geneticists, and administrative professionals who worked in a genetics clinic or laboratory with a GA. The inclusion criteria required that participants worked as or with a GA in Canada or the US for a minimum of six months between 2000 and 2018. We distributed a survey to genetic counsellors via the CAGC and NSGC e-mail listservs. We relied on snowball sampling to collect responses from GAs and other professionals who worked with GAs.

A total of 164 GAs and 139 individuals who worked with a GA met the inclusion criteria. Of the GA respondents, 26 worked in Canada and 138 worked in the US. The majority of GAs (83%) had an undergraduate degree, which reflects the educational requirements of most GA positions. GAs worked in a variety of specialties, with the most common being cancer, pediatrics, laboratory genetics, and prenatal. Almost half of the Canadian GAs (42%) had worked in the position for more than two years, compared to only 15% of American GAs. Of those currently employed as GAs, 84% were attending or planning to attend a genetic counselling program; of those no longer working as GAs, 90% were employed as a genetic counsellor or currently enrolled in a genetic counselling program. Roles and responsibilities were quite variable among GAs; in fact, there were few roles that were consistently reported across participants. Almost all GAs (92%) received some form of training and most felt that their training and prior education prepared them for the position. In total, respondents reported 144 GAs that are employed across North America, with the highest proportion of GAs in NSGC region 4.

This study demonstrates that GAs have been implemented in genetics services across Canada and the US and provides a detailed description of the workforce. Our research provides the foundation for future research studies, which could include GA education and further description of their roles.

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GC–116 Children during Paediatric Genetic Counselling Sessions: Barriers to Effective Communication and Strategies Employed

BRAHAM Lianna1,2, BABUL-HIRJI Riyana1,2, CHITAYAT David2,3, NEILSON Barbara4, WASIM Syed5, MACDONALD Heather1,6

1Department of Genetic Counselling, The Hospital for Sick Children, University of Toronto, Toronto.

2Division of Clinical and Metabolic Genetics, The Hospital for Sick Children.

3Department of Obstetrics and Gynecology, The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital.

4Department of Social Work, The Hospital for Sick Children.

5Fred A. Litwin Centre in Genetic Medicine, University Health Network & Mount Sinai Hospital.

6Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children.


Objective: In the paediatric genetic counselling setting, children often accompany parents to appointments. This may hinder effective communication between parents and genetic counsellors due to disruptions from the child as well as parents withholding information for fear of distressing their child. Previous research has only assessed parental perspectives of these issues. This study aimed to explore genetic counsellors’ perspectives on how the presence of children in the paediatric genetic counselling setting affects their ability to communicate with parents, and strategies they use to enhance communication.

Methodology: A quantitative survey with an embedded qualitative component was sent out to genetic counsellors in Canada, the U.S.A, the U.K., and Australia via e-mail. Participants were asked about the frequency of child-related challenges encountered in the genetic counselling setting and were provided with four vignettes relating to child disruptions and parental discomfort and asked to describe their counselling approach.

Results: Responses were received from 165 genetic counsellors. While complaining was the most common source of disruption, the disruptions causing the most parental distraction were children crying and wandering. Genetic counsellors perceived parents to experience more discomfort discussing certain topics in front of their child than the genetic counsellors themselves experienced discussing this information. Analysis of strategies utilized by genetic counsellors for challenging encounters revealed four recurring themes: (i) psychosocial skills, (ii) actions to remove barriers, (iii) modifying communication, and (iv) pre- or post-session contact with parents. Actions to remove barriers (e.g. having someone supervise the child in another room or finding something to keep the child occupied) were the most commonly utilized strategies overall.

Conclusion: Our results show that the presence of children in genetic counselling sessions can make communication with parents challenging; however genetic counsellors utilize a variety of effective strategies to try and manage these issues. The list of suggested strategies as elucidated by this study can be utilized by paediatric genetic counsellors to facilitate in the provision of counselling.

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GC–117 Educational resource requirements of healthcare providers offering prenatal screening

GILLESPIE Meredith K1,2, OKUN Nan3, RANDALL ARMEL Susan1,4, DOUGAN Shelley5, CHITAYAT David1,2,6, CARROLL June C7*, HAYEEMS Robin Z8,9*

1Department of Molecular Genetics, University of Toronto, Toronto, Canada.

2Division of Clinical and Metabolic Genetics, The Hospital for Sick Children.

3Department of Obstetrics and Gynaecology, Mt. Sinai Hospital.

4Division of Gynecologic Oncology, Princess Margaret Hospital.

5BORN (Better Outcomes Registry and Network) Ontario.

6The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital.

7Department of Family & Community Medicine, University of Toronto.

8Child Health Evaluative Sciences Program, Hospital for Sick Children Research Institute.

9Institute of Health Policy Management and Evaluation, University of Toronto.


Introduction: Since the introduction of Multiple Marker Screening (MMS) for aneuploidy in Ontario, prenatal genetic screening has become increasingly complex. This has affected quality and access to up-to-date counselling for pregnant people). Previous studies have found that health care providers (HCP) have difficulty understanding performance measures of prenatal screening (such as sensitivity and false positive rates), and in determining eligibility for and limitations of specific tests. To date, research has not determined the specific educational content and resource needs of Ontario HCPs.

Objectives: 1. Assess educational and resource needs of Ontario HCPs in the area of prenatal genetic screening. 2. Determine the most accessible mode of information delivery to inform Prenatal Screening Ontario’s (PSO) sustainable approach to provider education.

Methodology: A cross-sectional survey (one invitation followed by two reminders) was emailed to a convenience sample of Ontario obstetricians (OB), midwives (MW) and family physicians (FP) (n=901). The survey assessed HCPs’ confidence offering prenatal genetic screening, educational resource needs, and well as personal and practice demographics. Data were analyzed using descriptive statistics.

Results: To date, 152 responses have been received (response rate= 32% OB, 6% MW, 29% FP). Preliminary data show that HCPs report less confidence counselling on non-invasive prenatal testing (NIPT) (introduced in 2014), compared to traditional MMS. Most notably, 91% of HCP report confidence explaining the conditions screened by MMS, compared to 63% for conditions screened by NIPT. In addition, 91% of HCP report confidence explaining the MMMS test itself, compared to 76% for NIPT. As many as 62% of HCP report rarely/never accessing the PSO website for information, but going forward, 73% report that they are very/fairly likely to use resources similar to those currently available, such as targeted websites.

Conclusion: To provide a high-quality prenatal screening program, all HCPs must be well informed about the details of evolving prenatal screening options, and have continuous access to new information and guidelines as they become available. The results of our study suggest capacity-building efforts are warranted to boost provider confidence in some areas and that greater awareness about available resources is needed to ensure that providers can offer up-to-date patient-centered care.

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GC-118 Constitutional chromoanagenesis involving chromosome 1 in a fetus with multiple congenital anomalies

HUM Courtney1, PARKS William Antone2, SHANNON Patrick2, KOLOMIETZ Elena2, CHITAYAT David1,3

1The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

2Department of Laboratory Medicine and Pathobiology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada.

3Division of Clinical and Metabolic Genetics, Dept of Pediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.


Chromoanagenesis is a class of genomic alterations characterized by multiple structural variants confined to one or a few chromosomal segments through a single, catastrophic cell division event. We report a fetus with multiple congenital anomalies (MCA) and multiple deletions on chromosome 1p. A 29-year old primigravida woman presented at 24 weeks gestation with fetal ultrasound findings of oligohydramnios, agenesis of the corpus callosum (ACC), collapsed stomach and rocker bottom feet. The couple was non-consanguineous and family history was non-contributory. The patient elected for termination of pregnancy and the autopsy revealed ACC, poorly mineralized calvarium, cleft palate, short webbed neck, axillary pterygia, congenital diaphragmatic hernia, perimembranous VSD, bicuspid pulmonary and aortic valves, bifid ureters, rocker bottom feet, hypospadias and combined nephroblastomatosis. Chromosomal microarray analysis revealed three de novo deletions of the short arm of chromosome 1:

1) A 12.6 Mb deletion in chr. 1p13.3p12, a region which contains 176 RefSeq genes and 32 OMIM morbid genes.

2) A 1.1 Mb deletion in chr. 1p31.1p22, a region containing 18 RefSeq genes and 1 OMIM morbid gene.

3) A 4.9 Mb deletion in chr. 1p22.3p22.2, a region containing 35 RefSeq genes.

These represented three interstitial deletions on proximal end of chromosome 1p. Patients carrying deletions similar to the largest, 12.6 Mb deletion have been reported in DECIPHER to have IUGR, ACC, cardiac malformations, short stature, developmental delay and dysmorphic features. Several of the genes in the deleted region are associated with autosomal dominant disorders, such as Noonan syndrome, Alagille syndrome, neural tube defects and Epileptic Encephalopathy-32. To our best knowledge, similar reports of multiple microdeletions on chromosome 1 have not been reported.

Discussion: Chromoanagenesis has been predominantly discussed in the literature as a somatic genomic signature of cancer; however, reports are emerging of constitutional chromoanagenesis events in association with congenital disorders. Herein we describe multiple de novo microdeletions clustered on 1p in a fetus with MCA, suggestive of constitutional chromoanagenesis. Additional reports of constitutional chromoanagenesis, from the prenatal and pediatric settings, will further our understanding of the mechanisms and consequences of this phenomenon.

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GC-119 Apparently isolated mild fetal cerebral ventriculomegaly: a scoping review and recommendations for future research

HUDON Catherine, DE BIE Isabelle, CANALES Karen

McGill University, Montreal, Canada.


Objective: Mild fetal cerebral ventriculomegaly (MFCVM) is defined as a dilatation of between 10 and 15 mm of the cerebral ventricles as measured on a prenatal ultrasound. It can be difficult for health care professionals to know if certain investigations and interventions are effective or necessary once MFCVM has been detected, particularly when apparently isolated. This is due to multitude of factors, including a lack of long-term prospective studies evaluating atypical neurodevelopmental outcomes. The goal of the current scoping review was to clarify this uncertainty by estimating the frequency and severity of atypical neurodevelopmental outcomes once apparently isolated MFCVM has been detected and if differences in variables including dilatation size, stability, laterality, and symmetry affect the expected outcome.

Methodology: A comprehensive search strategy was formulated to capture most of the published work on apparently isolated MFCVM and subsequent neurodevelopmental outcomes across seven electronic databases. Inclusion criteria for the current review comprised of only considering those studies where children were followed until the age of 5 years and when prenatal scans were completed as of the year 2007 (i.e. when the guidelines for caliper placement for fetal cerebral ventricle measurement were established by the International Society of Ultrasound in Obstetrics & Gynecology; ISUOG).

Results: The search yielded a total of 9,759 possible citations, of which 11 studies were found to partially meet inclusion criteria. Corresponding authors from the 11 studies where contacted to request the subset of their data meeting criteria, and overall 11 cases where obtained from two studies. Of the 11 cases analyzed, the majority where found to have normal outcomes (n = 8, 72.7%), though at a smaller proportion than would be expected given previous research. Of the MFCVM variables of interest previously described, only data on laterality was available for all 11 cases and the number of unilateral MFCVM cases (n = 2) did not allow for meaningful comparison between groups.

Conclusion: The current review illustrates that few recent studies concerning apparently isolated MFCVM and neurodevelopment outcomes currently exist, particularly when taking into consideration long-term follow-up. The cases analyzed in the current review suggest that there may be a larger proportion of atypical neurodevelopment outcomes following the detection of MFCVM if follow-up is until an age when more subtle findings may become more apparent. The lack of relevant studies and the preliminary findings of the current review demonstrate the need for additional research on apparently isolated MFCVM in order to draw statistically significant conclusions with clinical utility.

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GC-120 The challenge of prenatal genetic counselling following the transfer of embryos with segmental mosaicism


North York General Hospital, Toronto, Ontario.


Introduction: Chromosomal mosaicism is present in 20-30% of blastocyst-stage embryos undergoing pre-implantation genetic testing for aneuploidies (PGT-A). Rates of chromosomal mosaicism at the time of amniocentesis tend to be much lower than this, suggesting chromosomal differences between the trophectoderm and inner cell mass, or the presence of an internal self-corrective mechanism of the embryos themselves. In vitro fertilization (IVF) using mosaic embryos has resulted in successful pregnancies, and some fertility clinics allow the transfer of mosaic embryos as a result. Unfortunately, there is a paucity of studies on postnatal outcomes in these cases. Prenatal genetic counselling has proven to be challenging, due to an inability to provide a precise risk assessment for fetal mosaicism.

Case Summary: In 2018, the Genetics Program at North York General Hospital received two referrals for genetic counselling for pregnancies conceived using mosaic embryos following IVF and PGT-A. Both of these cases involved mosaicism for a chromosome microdeletion. The counselling session included a discussion about embryo mosaicism and the variability of symptoms of the microdeletion depending on the level of mosaicism in the fetus, if any. The concepts of confined placental and fetal mosaicism were reviewed, as well as the benefits and limitations of NIPT, CVS and amniocentesis. One couple had been advised by their fertility clinic to have NIPT, and were surprised to learn that NIPT could not detect their specific segmental aneuploidy, and that the NIPT analyzes DNA from the trophectoderm, and may not necessarily represent the chromosome status of the fetus.

Both couples pursued amniocentesis with microarray analysis, and these results were normal, with no mosaicism detected. The limitations of amniocentesis were emphasized, in that testing of skin and bladder cells may not be representative of all cells in the fetus, and the inability of microarray to detect low-level chromosomal mosaicism. Detailed anatomy ultrasounds were normal in both cases. Though these normal results were reassuring, the patients remained concerned that fetal mosaicism could not be ruled out completely.

Conclusions: These cases illustrate the challenge of prenatal genetic counselling following the transfer of mosaic embryos. The information regarding the potential risks to the baby discussed in the counselling session is complex, and may not have been presented to the patient prior to the embryo transfer. The scarcity of outcome data in these cases adds an additional counselling challenge. These cases highlight the need for prenatal genetic counselling guidelines for patients whose pregnancies were conceived using mosaic embryos.

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GC-121 High mapping quality and coverage in the homologous PKD1 results in a high diagnostic yield

DAVIES Christine, VALO Satu, TALLILA Jonna, JALANKO Hannu, SISTONEN Johanna, KORPPOO Annakarin, GALL Kim, MUONA Mikko, SALMENPERA Pertteli, GENTILE Massimiliano, MYLLYKANGAS Samuel, ALASTALO Tero-Pekka, and KOSKENVUO Juha

Blueprint Genetics, Helsinki.


Purpose: Autosomal dominant polycystic kidney disease (ADPKD) is caused primarily by variants in PKD1 and PKD2. Genetic testing has become increasingly important in the management of ADPKD patients and their families; it identifies at-risk family members allowing for appropriate surveillance and therapies and identifies those who are not at risk to develop ADPKD and are therefore potential related donors for family members requiring kidney transplantation. Variants in PKD1 explain the majority of ADPKD cases, however, analysis of PKD1 is technically very challenging due to its large size, high GC-content and duplication of the first 33 exons with a high degree of homology (>98%) to six pseudogenes. We evaluated the diagnostic yield and performance of our in-house tailored Cystic Kidney Disease and Polycystic Kidney Disease Panels in patients referred for the indication of cystic kidney disease.

Methods: Next-generation sequencing (NGS) was performed using the IDT xGEN Exome Research Panel with added custom probes and the Illumina NovaSeq 6000 platform. This assay provides improved mapping quality and coverage in many difficult-to-sequence regions, including PKD1, compared to other NGS methods assessed in our laboratory. All pathogenic or likely pathogenic variants were confirmed with an appropriate orthogonal method with custom designed Sanger sequencing primers for the difficult-to-sequence region of PKD1.

Results: The mean sequencing depth of the 42 genes on the panels was 192x. PKD1 had both high mean sequencing depth (199x) and excellent mapping quality with 99.5% of the target nucleotides covered at least 20x when mapping quality threshold was set to 40 (correct read mapping with a probability of 99.99%). In the cohort of 131 index patients, a genetic diagnosis was established in 52% of cases with disease causing variants detected in 7 different genes. In 63% and 13% of the diagnostic cases, the disease-causing variant was identified in PKD1 and PKD2, respectively. Among all index patients identified to have PKD1 variants, pathogenic or likely pathogenic variants were detected in 70% (n=32) of cases. Interestingly, 84% (n=36) of the variants were located in the duplicated region of PKD1.

Conclusions: Our results demonstrate that our in-house NGS platform is well-suited for clinical diagnostics with comprehensive coverage in difficult-to-sequence regions of PKD1. The method provides a cost-effective diagnostic tool to simultaneously diagnose different types of variants including single nucleotide and copy number variants.

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GC-122 Peer Group Supervision Practices Among Canadian Genetic Counsellors


ELLS Courtney1, ANOJA Nancy2

1Department of Human Genetics, McGill University, Montreal, Quebec.

2Division of Medical Genetics, Department of Medicine, McGill University Health Center, Montreal, Quebec.


The benefit of peer group supervision (PGS) among genetic counsellors has been established; however, the current use of this practice and the process of establishing peer supervision groups remain relatively unknown. This study aimed to assess the current Canadian prevalence of peer group supervision among genetic counsellors, the structure of peer supervision groups, genetic-counsellor specific benefits, and barriers to establishing this practice. Fifty-four genetic counsellors participated in an online survey that assessed their participation in PGS in the past five years and their associated experiences. Respondents who both had and had not previously participated in peer group supervision were included in this study. Seven respondents with PGS experience provided consent to be re-contacted to participate in a follow up phone interview to provide further details regarding their opinions of their PGS practice. Qualitative data was analyzed using an inductive analysis approach to establish categories and sub-themes from the data. Peer group supervision was practiced by 38.9% of survey respondents in the past five years and involved variety of group structures. Reported benefits included peer learning, support, increased connection with colleagues, and identification of common challenges among group members. Barriers to peer group supervision, including PGS establishment, uptake, and continued participation, were identified to include lack of time, cost, undesired topics of group discussion, and interpersonal factors. All participants in PGS reported satisfaction with their current peer supervision group. Respondents who had not participated in PGS in the past 5 years reported a high likelihood of participation in PGS if it were to be available at their place of work. It is concluded that peer group supervision is a beneficial and satisfying support for genetic counsellors’ professional development, filling a role that is not otherwise addressed by other resources. Barriers remain when establishing and accessing peer group supervision and recommendations to address these barriers are provided.