Scientific Program


SUNDAY JUNE 19

1830-1930

Opening Keynote Speaker: Personalized Medicine

MONDAY JUNE 20

0845-1200

CSCC Symposium 1: Interpretation of Results

1330-1500

CCMG Trainees Platform Presentations

 

 

TUESDAY JUNE 21

0825-1230

CCMG Symposium 1: Cancer Genetics

0830-1130

CSCC Symposium 2: Diabetes Care

1345-1700

CSCC Symposium 3: Maternal Serum Screening

1330-1530

CCMG Concurrent Breakout Sessions
• Clinical, Metabolic, IEM
• Molecular Genetics/ WES
• Cytogenetics/aCGH

1600-1730

CCMG Workshop

 

 

WEDNESDAY JUNE 22

0830-1230

CCMG Symposium 2: The Genetics of Craniofacial Abnormalities

0900-1200

CSCC Symposium 4: Women’s Health

 

 

Opening Keynote Speaker: Personalized Medicine
Sunday June 19, 1830-1930

 

Chair: Gail Graham, Children’s Hospital of Eastern Ontario

 

Is This Really a Revolution?: Personalized Medicine and the Promise of Better Health

Speaker: Timothy Caulfield, LLM, FRSC, FCAHS, Canada Research Chair in Health Law & Policy, Trudeau Fellow and Professor, Faculty of Law and School of Public Health, research Director, health Law Institute, University of Alberta, Edmonton

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

  • Explain personalized medicine.
  • List expected benefits and harms.
  • Discuss the forces that lead to science hype.
  • List the potential risks associated with the push towards personalized medicine.
  • Discuss the limits of personalized medicine in the context of population health.

The idea that we are in the midst of a genetic revolution has been with us for decades. The latest iteration of this promise of paradigm-shifting transformation comes in the guise of “personalized medicine” – which, we are consistently told, will revolutionize our healthcare system and reduce the burden of chronic disease. But can personalized medicine live up to the hype? Will it really result in more healthy Canadians? In the presentation Caulfield will argue that there are reasons to be skeptical and that, in fact, the constant can hype hurt public perceptions of science, patient care and health policy.

 

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CSCC Symposium 1: Interpretation of Results
Monday June 20, 0845-1200

Chair: Christine Collier, Kingston General Hospital

 

The general objectives for the symposium are:

  • Critique the current information and resources provided to their clinical users that ensures appropriate result interpretation.
  • Discuss the progress, current concepts and applications of biological variation and reference change values with clinical colleagues.
  • Educate their clinical colleagues on the importance of understanding measurement uncertainty when interpreting single results or serial results from a patient.
  • Consider a variety of strategic approaches to assess and collaboratively manage laboratory result interpretation to optimize appropriate laboratory resource utilization, patient care and safety.

 

0845-0900

CSCC Award Presentations

 

0900-0950

Generation and application of data on biological variation

Callum Fraser, Senior Research Fellow, University of Dundee

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

  • State the types of biological variation of measurands in laboratory medicine and outline methods to derive the components of random within- and between-subject components.
  • List the applications of numerical data on the components of biological variation.
  • Describe the derivation of databases on biological variation and outline their advantages and disadvantages.
  • Relate current activities being undertaken to improve the validity of the database.
  • Assess newer concepts on the derivation and use of reference change values, the tools to examine changes in serial results from an individual.

Estimates of within- and between-subject biological variation are applied for many purposes, including assessing changes in serial results from an individual. Publications still regularly appear, demonstrating ongoing interest. Uses are facilitated by a database updated every two years. Criticisms exist regarding the validity of these data. This has led to publication of the methodology used to generate the database, and also a plea for harmonization and standardization of terms and symbols. Recent work in Europe aims to improve studies through a check-list and to review the existing database. The session will be of value to: all professionals in laboratory medicine.

 

1020-1110

Uncertainty of measurement: application to laboratory medicine

Kent C. Dooley, Clinical Director – BC Chemistry, LifeLabs

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

  • Understand the concept of Uncertainty of Measurement(UM) and its connection to ISO Standards.
  • Understand the basic principles and tenants of GUM (Guide to the Uncertainty of Measurements).
  • Apply GUM principles in the Clinical Laboratory to determine UM.
  • Appropriately use UM values in the context of the clinical laboratory.

Laboratories are now expected to provide uncertainty of measurement (UM) values for each of the tests that they report. UM can be considered as an adjunct to traceability. The combination of the two provides the most complete definition of trueness of a laboratory determination. The Guide to the Uncertainty of Measurement(GUM) which is sponsored by ISO and the IFCC, provides the tenets of how UM should be determined and strategies for determining it. The bottom up and top down approaches to Uncertainty of Measurement will be described. Then the issue of how UM can be determined in the context of the clinical laboratory will discussed. Examples from regulatory, standards and professional bodies will be referenced. How the UM values determined for a laboratory’s individual tests can and should be used will then be discussed. The target audience is Clinical Chemists, Laboratory Quality Assurance managers and Technologists.

 

1110-1200

Translational Omics: Over-Testing and Over-Treatment

Vathany Kulasingam, Clinical Biochemist, University Health Network

 

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

  • Explain the concept of precision medicine, as it relates to next-generation omics technologies.
  • Discuss the opportunities and challenges in delivering these omic technologies to improving patient care.
  • Summarize over-diagnosis and over-treatment and the lessons learned from cancer screening programs.

High-throughput technologies such as next-generation genomics, transcriptomics and proteomics are capable of generating massive amounts of data quickly, and at relatively low costs. It is tempting to use this data for various medical applications including preclinical disease detection and for prediction of disease predisposition. In this presentation, I will illustrate the opportunities and challenges that we will face when delivering these omics technologies to improving patient care. The session will be of value to both clinical chemists and medical geneticists.

 

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CCMG Trainees Platform Presentations
Monday June 20, 1330-1500

 

1330-1342

MG-200 The clinical utility of targeted next generation sequencing in prenatal congenital heart disease

Yanwei Xi, Alberta Children’s Hospital

 

1342-1354

MG-201 7p22.3p22.2 microdeletion is associated with variable developmental delay and characteristic facial features

Andrea Yu, Children’s Hospital of Eastern Ontario

 

1354-1406

MG-202 A new case of 5q31 microdeletion syndrome and putative causative genes

Caitlin Chang, Alberta Children’s Hospital

 

1406-1418

MG-203 ALG9-CDG: New Clinical Case and Review of the Literature

Kellie Davis, Alberta Children’s Hospital

 

1418-1430

MG-204 A rare four break balanced reciprocal insertional chromosomal translocation – a case report

Kathleen Bone, Alberta Children’s Hospital

 

1430-1500

Refreshment Break

 

1500-1512

MG-205 Novel WDR45 mutation identified in patient diagnosed with Beta-propeller protein associated neurodegeneration

Marisa Chard, University of Calgary

 

1512-1524

MG-206 Novel HPD mutations identified in First Nations Canadian siblings diagnosed with Tyrosinemia Type III

Alison Eaton, University of Calgary

 

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CCMG Symposium 1: Cancer Genetics
Tuesday June 21, 0830-1230

 

0830-0910

The Emerging Genetic Basis of Childhood Cancer Susceptibility

David Malkin, Professor of Pediatrics, Division of Hematology/Oncology, Hospital for Sick Children

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

  • Recognize a constellation of cancers and identify the genotype associated with that constellation.
  • Consider the challenges in genetic testing and tumor surveillance in children at risk of cancer.
  • Formulate a strategy to apply emerging technologies (like NGS) to diagnosis of cancer susceptibility syndromes.

The etiology of at least 10% and perhaps as many as 40% of cancers of childhood maybe attributed to heritable genetic factors. This presentation will highlight the recent progress made in clarifying cancer predisposition phenotypes, correlating genetic and genomic alterations with these phenotypes, and utilizing novel approaches for early cancer detection in genetically at-risk children. This session will be valuable to medical geneticists, genetic counselors, cancer geneticists and pediatricians.

 

0910-0950

Inherited Susceptibility to Colorectal Polyps and Colorectal Cancer: A Review Focused on New Mendelian Findings

William Foulkes, Professor, Departments of Medicine, Human Genetics and Oncology, McGill University; Director, Program in Cancer Genetics, McGill University

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

  • Describe the new findings in hereditary GI cancers.
  • Distinguish between different syndromes.
  • Examine pedigrees and determine which gene is likely to be responsible.
  • Implement genetic testing for hereditary GI cancers.
  • Recognize the varied manifestations of APC mutations.
  • Critique next generation sequencing as a diagnostic tool.

In this talk, I will start by outlining what is known – the well known syndromes – FAP (APC) and Lynch (mismatch repair genes). Then I will focus on what is new. The talk will focus on new findings in APC (exon 1B point mutations and the GAPPS variant of FAP) as well as new genes for colorectal polyps and cancer – POLE/POLD1 (PPAP), GREM1 (HMPS) and NTHL1 – a new autosomal recessively inherited susceptibility with a broad spectrum of tumors implicated. Other important but slightly better known conditions, CMMRD and MAP, will also be discussed. I will finish by listing all the known mendelian causes of colorectal polyps.

 

0950-1030

Hereditary Pancreatic Cancer

George Zogopoulos, Assistant professor, Surgery, McGill University

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

  • Describe the incidence and current treatment landscape of pancreatic cancer.
  • Describe causes of hereditary pancreatic cancer.
  • Provide an overview of emerging therapies for pancreatic cancer subtypes.
  • Discuss genetic testing for pancreatic cancer.
  • Consider the evidence for clinical screening of individuals at increased risk for pancreatic cancer.

 

1030-1100

Refreshment Break

 

1100-1140

Breast and Ovarian Cancer Genetics: An Update for 2016

William Foulkes, Professor, Departments of Medicine, Human Genetics and Oncology, McGill University; Director, Program in Cancer Genetics, McGill University

 

In this presentation, my focus will be on three areas – 1) BRCA1/2: going beyond risk assessment, 2) Going beyond BRCA1/2, 3) Population testing for hereditary cancer susceptibility. In the first section, I will talk about DNA repair and its central role in hereditary breast cancer, and especially how this has led to novel therapies which are associated with the presence of germline mutations. I will outline four key clinical questions. I will then list the key genes that are accepted as bona fide breast cancer genes, other than BRCA1/2. I will consider the candidacy of each gene in turn. Then I will briefly discuss predisposition to ovarian cancer. In the final section I will discuss the pros and cons of population-based genetic testing. I will compare and contrast founder genetic testing for cancer susceptibility with more broad-based testing. To finish, I will compare different models of testing for cancer susceptibility.

 

1140-1220

Dissecting the Clinical Genomics of Therapy-Resistant Prostate Cancer Through Liquid Biopsy

Alexander Wyatt, Senior Research Scientist, Vancouver Prostate Centre, Assistant Professor, Department of Urologic Sciences, University of British Columbia

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

  • Describe the landscape of germline and somatic alterations that contribute to castration-resistant prostate cancer
  • List genomic alterations detectable in patient liquid biopsies that are associated with resistance to Androgen Receptor (AR) targeted therapy
  • Discuss the potential for circulating cell-free tumor DNA (ctDNA) to be a biomarker for predicting patient response to AR-targeted therapy
  • Summarize the spectrum of clinically-informative changes that are detectable in patient ctDNA and how these alterations can aid clinical trial enrichment

This presentation will explore the potential for circulating cell-free tumor DNA (ctDNA) to aid prostate cancer patient treatment decisions, clinical trial enrichment, and advance our understanding of disease biology. Topics will include the recently revealed molecular landscape of advanced prostate cancer, the previously under-recognized germline contribution to aggressive disease, and clinically-relevant breakthroughs in liquid biopsy analysis that have provided clues to predicting therapy resistance. The session will be of value to: medical geneticists and oncologists, and well as those studying hereditary cancer.

 

1220-1230

Closing Remarks

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CSCC Symposium 2: Diabetes Care
Tuesday June 21, 0830-1130

Chair: Curtis Oleschuk, Diagnostic Service of Manitoba

 

The general objectives for the symposium are:

  • Demonstrate the benefits to patient health with a patient-centered model for delivery of care to chronic diseases and treatment associated with diabetes.
  • Describe the improvements to the care of patients with chronic kidney disease that has resulted from standardization within and outside the clinical laboratory.
  • Provide an update on the Islet Cell Transplantation and its importance in the long term management of patients with diabetes.
  • Describe how diabetes management is utilizing testing that is patient centered, both in terms of performing the test and managing the information, to improve patient health and performance.

 

0830-0920

Laboratory based interventions to improve clinical care: examples from chronic kidney disease

Brenda Hemmelgarn, Professor and Head, Dept of Community Health Sciences, University of Calgary

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

  • Describe the relevance and impact of eGFR reporting.
  • Discuss the importance of laboratory based interventions in CKD care.
  • Identify opportunities for integration of laboratory and clinical activities to enhance patient care and outcomes.

Chronic kidney disease (CKD) is defined by estimated glomerular filtration rate (eGFR) using serum creatinine. Therefore this laboratory measure is important to define the presence of CKD. There have been significant changes over the past decade in the identification and management of patients with CKD based on their eGFR. Activities undertaken based on these laboratory measures therefore have potential to enhance patient care and outcomes. This session will provide an overview of the relevance and importance of eGFR reporting, as well as provide examples of lab based interventions which have been studied and their impact on patient care. Other opportunities for integration of laboratory and clinical activities to enhance patient care and outcomes will be discussed. This session will be of value to clinical chemists, other members of laboratory medicine, clinicians and allied health care professionals.

 

0920-1010

Diabetes Care: Islet Transplantation – where are we?

Peter Senior, Islet Transplant Program, University of Alberta

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

  • List indications and contraindications for islet transplant.
  • Confidently explain the risks and benefits of islet transplantation.
  • Summarize challenges and opportunities for alternate beta cell replacement strategies.

The Edmonton protocol was a major step forward in diabetes therapy permitting insulin independence in 7 consecutive patients with type 1 diabetes. Originally published in 2000, more than 230 patients have now been treated in Edmonton – the largest single centre experience in the world. Substantial improvements have been made to increase the safety of the procedure and tolerability of immunosuppression – as well as improving long term great survival. With long term file up now extending beyond 15 years we can better quantify the long term risks of immunosuppression in this population as well as the impact on mortality, renal function and diabetes complications. We have begun to explore alternate sites for islet transplant as well as initiating first in human clinical trial of macro encapsulated stem cell derived pancreatic progenitor cells. The session will be of interest to clinical biochemists, immunological, and others interested in diabetes, transplantation or stem cell therapies.

 

1040-1130

Patient Centered Testing

Philip Chen, Sonic Healthcare USA

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

  • Describe approaches that are unique to clinical laboratories to identify population care management gaps and needs.
  • Deploy interventional strategies employing clinical decision support and patient engagement to target gaps in individual care and improve clinical workflow efficiency.
  • Anticipate and measure clinical and financial outcomes when deploying intervention programs.
  • Leverage laboratory data and direct patient care infrastructures to better integrate with healthcare provider ecosystem.

As US healthcare rapidly transitions from volume-based reimbursement to value-based, clinical laboratories are being challenged to focus on patient outcomes and provide better integration with other healthcare partners in pre- and postanalytical operations outside of the laboratories. In this session, specific use cases will be discussed to illustrate how a laboratory uses informatics-driven approaches to identify specific patient care gaps, initiates direct patient engagement and provides an alternative clinical workflow to improve care efficiency and clinical and financial outcomes. The session will be of value to: pathologists, lab medical directors, administrative directors, managers clinical data scientists, CMO/CMIO’s, care managers/coordinators.

Breakout Sessions
Tuesday June 21, 1330-1530

 

Clinical Breakout – Clinical; metabolic, IEM

Oana Caluseriu, Assistant professor, Department of Medical Genetics, University of Alberta

Komudi Siriwardena, Associate Professor, Department of Medical Genetics, University of Alberta, Stollery Children’s Hospital

 

Molecular Genetics/WES

Dennis Bulman, Senior Scientist, CHEO Research Institute & Newborn Screening Ontario Affiliate Member, Regenerative Medicine Program, OHRI Full Professor, Department of Pediatrics, Faculty of Medicine, University of Ottawa

 

Cytogenetics/aCGH

Judy Chernos, Associate Professor, Department of Medical Genetics, University of Calgary, Site Head, Genetic Laboratory Services, Cytogenetics Laboratory

 

CCMG Workshop – An update on Genetics Computer Programs
Tuesday June 21, 1600-1800

 

1600-1630

FDNA

Dekel Gelbman, Chief Executive Office, FDNA Accessible Genetics, Boston

 

1630-1700

Phenotip

Michael Brudno, Genetics & Genome Biology, University of Toronto

 

1700-1730

Matchmaker Exchange

Michael Brudno, Genetics & Genome Biology, University of Toronto

 

1730-1800

WES Analysis

Jillian Parboosingh, Alberta Children’s Hospital, Alberta Health Services

 

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CSCC Symposium 3: Maternal Serum Screening
Tuesday June 21, 1345-1700

Chair: Kareena Schnabl, University of Alberta Hospital

 

The general objectives for the symposium are:

  • Evaluate the biochemical and molecular testing options available for prenatal screening of trisomies in Canada.
  • Describe and appreciate the technical aspects of cell free fetal DNA.
  • Outline the clinical impact of the inclusion of cell free fetal DNA testing to current testing guidelines and describe approaches taken in different Canadian provinces.
  • Appreciate the impact of the PEGASUS initiative on clinical practice.

 

1345-1400

CSCC Award Presentations

 

1400-1450

Prenatal screening for Down syndrome: The role of Biochemical markers

Nathalie Lepage, Head, Biochemical Genetics Laboratory, Children’s Hospital of Eastern Ontario

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

  • Describe the markers used for various protocols for Down syndrome screening.
  • Compare the screening performance of the various protocols.
  • Estimate the impact of patient characteristics on screening performance.

At the onset of prenatal screening for Down syndrome, there was a limited number of biomarkers available for risk assessment. However major changes have occurred in this field over the past few years, as we implemented new markers, biochemical and sonographic; and expanded the screening windows to include first and second trimester samples in the risk calculation. This presentation will present the main options based on maternal serum collected during the first and the second trimesters of pregnancy. Other aspects that will be presented will be the impact of accurate patient description, i.e. smoking, patient weight, ethnic background, etc. The session will be of value to laboratory scientists and physicians, medical laboratory technologists, medical geneticists and laboratory managers.

 

1520-1610

Technical aspects and quality features of the NIPT noninvasive prenatal test

Barry Hoffman, Mount Sinai Hospital

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

  • Describe the common elements of the Noninvasive Prenatal Test [NIPT].
  • Compare the different NIPT assay designs available comercially to determine Trisomy 21.
  • Discuss analytical, physiological and clinical features that bear on the quality and rigour of NIPT.
  • Itemize strengths and limitations of NIPT.
  • Summarize briefly the clinical performance of NIPT.
  • Explain how fetal aneuploidy can be determined from cell free fetal DNA fragments circulating in the maternal blood.

Noninvasive Prenatal Testing (NIPT) assesses cell free fetal DNA fragments circulating in maternal blood to determine the copy number of fetal chromosomes and hence whether aneuploidy, in particular Trisomy 21, 18 or 13, is present. Clinical performance is significantly better than obtained with conventional screening, hence the strong interest in and rapid adoption of NIPT. The presentation will focus primarily on analytical aspects of the NIPT test. Specifically, it will describe the common elements of the NIPT assay, highlight the “Next Gen” simultaneous processing of millions of DNA fragments in parallel, point out differences in the NIPT assays offered commercially, emphasize analytical, physiological and clinical factors that influence the quality of the assay result, discuss strengths and limitations of NIPT, and illustrate how the test is reported. The session will be of value to clinical chemists, other laboratorians, physicians, genetic counselors and technologists who seek to understand the technical basis of the NIPT assay and factors that bear on the quality of the NIPT result.

 

1610-1700

Options for prenatal screening for trisomies in Canada

Radha Chari, Chair Department Ob-Gyn, Zone Department Head, University of Alberta, Alberta Health Services

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

  • Compare the different options for screening.
  • Explain NIPT.
  • Compare NIPT to other biochemical screening options.
  • Summarize different approaches available in Canada.

The objectives of this presentation are to:
– Evaluate the biochemical and molecular testing options available for prenatal screening of trisomies in Canada
– Describe and appreciate the technical aspects of cell free fetal DNA
– Outline the clinical impact of the inclusion of cell free fetal DNA testing to current testing guidelines and describe approaches taken in different Canadian provinces
– Appreciate the impact of the PEGASUS initiative on clinical practice The rate of evolution for prenatal genetic screening for trisomies over the past 20 years has evolved and changed more than possibly any other area in medical practice.
We have gone from the basic approach of invasive testing based on maternal age alone as the primary screen in the 1990’s to the ability to offer maternal blood testing alone as a possible primary screen in 2016. This presentation will focus on the various prenatal screening options for trisomies available today. This will also include a review of NIPT and it’s implications in the current screening landscape, and the role for integrating this into clinical practice, as well as briefly discuss the PEGASUS initiative. This session will be of value to medical geneticists and other involved in prenatal genetic screening

 

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CCMG Symposium 2: The Genetics of Craniofacial Abnormalities
Wednesday June 22, 0830-1230

 

0830-0910

The embryology of normal and abnormal craniofacial development

Kathleen Sulik, Professor, Department of Cell Biology and Physiology, University of North Carolina School of Medicine

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

  • Summarize major developmental events preceding lip and palate closure.
  • Discuss the developmental relationships between the face and brain.
  • Discuss gene/environment interactions as a basis for craniofacial malformations.
  • Discuss the developmental basis for commonly occurring as well as unusual facial clefts.

The focus of this presentation will be on the morphological changes that shape the craniofacies and that occur between the 3rd and 9th weeks of human gestation. Scanning electron micrographs will facilitate appreciation of the numerous facial growth centers and their relationship to typical and unusual facial clefts. The developmental basis for holoprosencephaly will also be discussed, as will pertinent gene/environment interactions underlying this spectrum of craniofacial defects. The session will be of value to medical geneticists.

 

0910-0950

Coffin-Siris and Nicolaides-Baraitser syndromes and related disorders

Dagmar Wieczorek, University Clinic Düsseldorf, Heinrich-Heine-University

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

  • List the clinical findings for both syndromes.
  • Summarize the genes causative for both syndromes.
  • Discuss and compare differential diagnoses.

The SWI/SNF complex mobilizes nucleosomes and remodels chromatin in an ATP dependent manner. It is well known that mutations within the SWI/SNF complex lead to cancer, but also to unspecific intellectual disability and to Coffin-Siris (CSS) and Nicolaides-Baraitser syndromes (NCBRS). De novo heterozygous mutations have been identified in different components of the SWI/SNF complex that cause CSS or NCBRS. The mutation spectrum and the clinical features of patients with mutations in the ARID1A, ARID1B, SMARCB1, SMARCE1, SMARCA4 and SMARCA2 genes will be discussed in detail. Mutations in PHF6, which encodes for a protein that interacts with the nucleosome remodeling and deacetylase complex (NuRD), lead to a specific phenotype in girls resembling CSS in early childhood. This entity will be discussed as an important differential diagnosis. Exome analyses in patients without mutations in the SWI/SNF complex revealed other differential diagnosis, which had not been considered after clinical evaluation of the patients: Wiedemann-Steiner, Kabuki and Adams-Oliver syndromes. In summary, the phenotypic and genotypic spectrum of SWI/SNF related disorders will be overviewed and important differential diagnosis will be discussed.

 

0950-1020

Refreshment Break

 

1020-1100

Nager and CCMS syndromes: prototypical spliceosomomathies

G. Francois Bernier, Associate Professor, Department of Medical Genetics; Director, Clinical Genetics, Alberta Childrens’ Hospital

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

  • Describe the cardinal clinical features of Nager and CCMS syndrome.
  • Describe the genetic basis of these spliceosomopathies , with an emphasis on genetic counselling.
  • Discuss potential links between splicing and craniofacial and skeletal development.

Nager syndrome is a classic acrofacial dysostosis whose etiology remained elusive until a whole exome sequencing (WES) approach by our group identified the splicing factor SF3B4 as the causative gene in the majority of cases. Nager syndrome is characterized by micrognathia, midface hypoplasia and ear malformations, along with highly variable limb anomalies including radioulnar synostosis and radial ray deficiencies. Long term outcomes are often favorable with most cases having normal intelligence. All cases thus far have been due to heterozygous mutations. Ongoing efforts including whole genome sequencing of SF4B4 negative cases have thus far failed to identify additional genes. Cerebrocostomandibular syndrome is also a classic craniofacial skeletal syndrome with micrognathia and classic posterior rib gap anomalies with a narrow chest. Aggressive early support of respiratory issues is crucial and long term outcomes are also favorable with most children have normal intelligence. Again an WES approach identified heterozygous mutations in a highly conserved splicing factor (SNRPB) as the etiology in most cases. The mutations affect the autoregulation of SNRPB, suggesting that subtle perturbation of splicing efficiency results in the phenotype. Although most sporadic cases are due to de-novo mutations, non-penetrance has been observed in three families. These conditions are part of an increasing group of syndromes due to mutation of core splicing factors (so called spliceosomathies,) and ongoing research in our group is aimed at identifying additional genes as well as delineating the pathogenic mechanisms underlying non-penetrance, as well as the developmental phenotype.

 

1100-1140

Ribosomopathies and spliceosomopathies – an update

Dagmar Wieczorek, University Clinic Düsseldorf, Heinrich-Heine-University

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

  • List conditions belonging to the ribosomopathies and spliceosomopathies.
  • Explain the clinical features of ribosomopathies and spliceosomopathies.
  • Summarize causative genes.
  • Compare different conditions belonging to ribosomopathies and spliceosomopathies.

The craniofacial anomalies observed in the mandibulofacial dysostoses (MFDs) result from defective development of the first and second branchial arches. The craniofacial anomalies comprise downslanting palpebral fissures, coloboma of the lower eyelid, hypoplasia of the zygomatic complex, micrognathia, and microtia, which is often associated with hearing loss. At least 13 different types of MFD have been clinically described and this number is likely to rise. Due to the causative gene/s identified for the different conditions they either belong to the ribosomopathies or to the spliceosomopathies. An update will be given.

 

1140-1220

The importance of global matchmaking to define new genetic syndromes: Examples from craniosynostosis

A. Micheil Innes, Associate Professor, Department of Medical Genetics, Alberta Childrens’ Hospital

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

  • Discuss the importance, and various examples, of global matchmaking as a means to new gene discovery.
  • List the clinical features associated with de novo loss of function mutations in HNRNPK (Au-Kline syndrome).
  • List the clinical features associated with autosomal recessive mutations in DPH1 (DEDSHH, Loucks-Innes syndrome).

The advent of next generation sequencing has led to an increasing rate of clinical diagnosis for rare disease patients as well as the discovery of hundreds of novel disease genes. Nevertheless for many rare disease patients a specific diagnosis is not obvious after whole exome sequencing. In some instances however, a small number of candidate genes merit further attention. Ultimately, identifying patients with similar phenotypes and mutations in the same gene remains essential to conclude that a specific gene is associated with a given phenotype. For rare diseases, this requires global participation. Herein, using two specific examples of patients studied in Calgary with rare craniofacial syndromes associated with craniosynostosis, we discuss how ‘old’ and ‘new’ methods of matchmaking were used to identify novel genes. The presentation will briefly review what is currently known about the genetics of craniosynostosis including both ‘common’ and ‘rare’ syndromes, with a focus on two novel conditions. This session will be of value to medical geneticists (clinical and lab based) and medical genetics trainees.

 

1220-1230

Closing Remarks

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CSCC Symposium 4: Women’s Health
Wednesday June 22, 0900-1200

Chair: Mathew Estey, DynaLIFEDx

 

The general objectives for the symposium are:

  • Describe the broad range of unique health issues facing women, including their biochemical and physiological etiologies.
  • Discuss the role of the clinical laboratory in improving women’s health outcomes.
  • Compare the importance, challenges and pitfalls of gender identification during the laboratory testing process.

 

0900-0950

The importance of studying women’s health

Ann M. Gronowski, Professor Pathology and Obstetrics & Gynecology, Washington University School of Medicine

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

  • Discuss the differences between women and men that affect their health.
  • List the reasons why more research has not been done on women in the past.
  • Describe what is needed to advance women’s health.
  • Explain the important role of the clinical laboratory in improving women’s health outcomes.

What’s different about women’s health? Certainly, some of the unique health issues that face women are related to reproductive health and pregnancy. However, many conditions that affect both sexes have distinct manifestations in women including cardiovascular disease, osteoporosis, and anemia to name a few. Until recently, much of the medical literature that was published focused on predominantly male populations. Slowly, we have come to appreciate the differences in normal physiology and abnormal pathology between men and women. This presentation will discuss the health-related differences between women and men and discuss what is needed to advance women’s health moving forward. This session will be valuable to physicians, laboratorians, researchers and anyone interested in issues affecting women’s health.

 

1020-1110

Women’s CV Health – we’ve come a long way baby – or have we?

Beth Abramson, Associate Professor of Medicine, University of Toronto

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

  • Understand the leading health threat facing women.
  • Review cardiac risk assessment in the post menopausal woman.
  • Understand risk reduction strategies for women.

Cardiovascular disease is a leading health threat for Canadian women. The influence of gender on the effect of any intervention or treatment in the cardiac patient (and elsewhere in medicine) is important. Women are 7-10 years older than men when they present with acute coronary syndromes, and often are sicker with more co-morbidity. Biases in care between the genders have been documented and corrected to some degree in the past decade. (46-51)Subsequent studies have shown that women have been under-diagnosed, under-referred, and under treated compared to men in the cardiac field.(15;52;53) For the first time in 30 years, women have caught up to men when it comes to the number of deaths from cardiovascular disease. A potential factor in this “gender – gap” is that risk is underestimated in women. This session will deal with CV risk assessment and risk reduction in women. The concept of “global risk assessment” will be reviewed and applied to women to reinforce optimal CV care for appropriate risk reduction and treatment.

 

1110-1200

Providing effective healthcare and laboratory testing to the transgender community

Dina N. Greene, Assistant Professor, University of Washington

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

  • Illustrate the differences between gender and sex.
  • Give an example of healthcare discrimination towards transgender individuals.
  • Describe the barriers involved in providing adequate laboratory medicine to the transgender population.
  • Highlight the standards of care for treating transgender individuals with gender dysphoria.

The transgender population challenges social norms because they personify the differences between biological sex and gender. Meaning, biological sex, defined by anatomical characteristics and chromosomal make-up, can be inequivalent to a person’s gender identity, defined as a person’s psychological identification as male or female, categories that are socially and culturally constructed and maintained. A transgender identity is not a disease. However, many transgender individuals have experienced severe social stigma and pressure that manifest as gender dysphoria or extreme distress over gender identity. A person’s transition may include physical elements (hormone replacement therapy, surgeries), although for many transgender individuals, transitioning socially (without hormones/surgeries) meets their needs. Barriers to healthcare, both front-of-the-house and in the laboratory, prevent an overwhelming majority of transgender-identified individuals from accessing the most basic medical care. The laboratory has medically significant reasons for classifying specimens based on biological sex, which are both clinical and pragmatic. For example, calculation of eGFR requires the input of sex to accurately assess kidney function. Similarly, healthy hematologic parameters are significantly different between cisgendered-men and cisgendered-women. Where does the transgender population medically fit into these definitions? How can a physician adequately assess anemia in an individual who has transitioned from one gender to another – especially considering that the goal of an individual’s transition is not defined by a medical procedure or therapy, but by a psychological ease that is person-specific? Adding to the complexity, most laboratory information systems (LIS) have limited capabilities to extend beyond a gender or sex binary, a failure that can have medical and emotional consequences for patients. Finally, how does a phlebotomist respond respectfully to a person who visually appears to not be the sex printed on their bar-code label? A visual sex/gender discrepancy might cause sample processing errors and lead to mislabels, lost specimens, or pre-analytical errors. These overarching generalizations that the laboratory considers standard for specimen collection and result reporting affects transgender patient’s access to quality health care. This presentation will discuss the differences between sex and gender, expanding on the limitations of the sex/gender binary. Pulling examples from transgender individuals’ healthcare experiences the talk will illustrate how both the pre-analytical and post-analytical generalizations could be improved when serving this population. Second, clinical examples highlighting the value of sex-specific reference ranges, and encourage solutions for integrating these clinical parameters, while respecting gender identity will be presented. The few studies that have established reference intervals in transgender populations will be discussed. Third, the current standard-of-care guidelines for managing transgender patients will be discussed using case-based examples to give particular emphasis to the role of the laboratory in guiding management. Combined, this symposium aims to de-stigmatize discrepancies between gender and sex, while inviting solutions as to how the clinical lab can embrace these differences. This session is intended for pathologists, lab directors, clinical chemists, technologists, and IVD industry scientists.

 

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