Christina Honeywell

Recommendations for the use of genetic testing in the clinical evaluation of inherited cardiac arrhythmias associated with sudden cardiac death: Canadian Cardiovascular Society/Canadian Heart Rhythm Society joint position paper.

The era of gene discovery and molecular medicine has had a significant impact on clinical practice. Knowledge of specific genetic findings causative for or associated with human disease may enhance diagnostic accuracy and influence treatment decisions. In cardiovascular disease, gene discovery for inherited arrhythmia syndromes has advanced most rapidly. The arrhythmia specialist is often confronted with the challenge of diagnosing and managing genetic arrhythmia syndromes. There is now a clear need for guidelines on the appropriate use of genetic testing for the most common genetic conditions associated with a risk of sudden cardiac death. This document represents the first ever published recommendations outlining the role of genetic testing in various clinical scenarios, the specific genes to be considered for testing, and the utility of test results in the management of patients and their families.

Factors associated with knowledge of and satisfaction with newborn screening education: a survey of mothers

Purpose:Effective parental education about newborn blood-spot screening may facilitate prompt follow-up, reduce psychosocial harms, and promote trust in screening programs. However, little is known about the aspects of education delivery and content that are of most importance for fostering understanding and meeting parental expectations. We aimed to identify elements of newborn blood-spot screening education and their associations with mothers’ knowledge and satisfaction levels.Methods:We conducted a survey (by mail) of 1,712 mothers who were residing in Ontario, Canada, and whose infants had recently undergone newborn blood-spot screening.Results:We received 750 completed questionnaires (response rate 47%). Factors associated with respondents’ higher knowledge of newborn blood-spot screening were higher level of education (odds ratio = 2.79), English being spoken at home (odds ratio = 1.96), receiving an information sheet at the time of newborn blood-spot screening (odds ratio = 1.57), and receiving information about how to interpret the results (odds ratio = 2.65). Factors associated with being satisfied were: receiving information prenatally (odds ratio = 2.35), from a health-care professional (odds ratio = 4.54), or from an information sheet at the time of newborn blood-spot screening (odds ratio = 1.72); and receiving messages about the purpose of screening (odds ratio = 3.78), the communication process (odds ratio = 2.57), the interpretation of the results (odds ratio = 4.19), and sample-handling methods (odds ratio = 3.13).Conclusion:Promoting mothers’ understanding and meeting their expectations with respect to education about newborn blood-spot screening may require greater engagement with prenatal providers. It also calls for a greater emphasis on communicating with mothers about how blood samples are handled and about the meaning of the test results.Genet Med 2012:14(12):963–970

A family genetic risk communication framework: guiding tool development in genetics health services

Family communication of genetic risk information is a complex process. Currently, there are no evidence-based interventions to help genetics professionals facilitate the process of disclosure within families. This study was designed to create a framework to assist in the development of tools to support patients in communicating genetic risk information to family members. A systematic review identified the factors relevant in communicating genetic risk information in families. A guiding theory for the proposed framework was selected and populated with the factors identified from the review. The review identified 112 factors of relevance. The theory of planned behaviour was selected to guide framework development, organising the framework in terms of the patient’s attitudes about disclosure, perceived pressure to disclose and perceived control over disclosure. Attitudes about disclosure are influenced by a desire to protect oneself or family members, and the patient’s perceptions of relevance of the information for family members, responsibility to disclose, family members’ rights to information and the usefulness of communicating. Perceived pressure to disclose information is shaped by genetic professionals, family members and society. Perceived control over disclosure is affected by family relationships/dynamics, personal communication skills, the ability of the patient and family to understand the information and coping skills of the patient and family member. The family genetic risk communication framework presents a concise synthesis of the evidence on family communication of genetic information; it may be useful in creating and evaluating tools to help genetic counsellors and patients with communication issues.

National Association of Medical Examiners Position Paper: Retaining Postmortem Samples for Genetic Testing

Sudden unexpected death is typically diagnosed in infants, children, teenagers, and young adults following completion of an autopsy that fails to identify a cause of death or when autopsy suggests a potentially genetic cause of death in an individual less than 40, such as cardiomyopathy or aneurysm. Such deaths may be a result of genetic abnormalities that are unable to be diagnosed by gross or microscopic inspection, but may be detectable by molecular studies. Unfortunately, the ability to perform postmortem genetic testing is frequently hindered by lack of an appropriate specimen following completion of an autopsy. This paper provides recommendations developed by the National Association of Medical Examiners with the assistance of genetic counselors. The recommendations establish procedures to facilitate postmortem genetic testing and DNA banking by health care professionals assisting families who have experienced sudden death in young relatives by clarifying proper sample acquisition and storage. Additionally, recommendations for discussion with surviving family members and test planning are provided. The objective of these recommendations is to ensure that postmortem samples suitable for DNA banking are retained, allowing at risk family members improved detection of potentially treatable genetic diseases.

Activity intensity during free-living activities in children and adolescents with inherited arrhythmia syndromes: assessment by combined accelerometer and heart rate monitor.

Background— International guidelines recommend restriction of activities for many children and adolescents with inherited arrhythmia syndromes to moderate activity (<7 metabolic equivalents [METs]). We hypothesized that moderate levels of intensity would be exceeded during free-living daily activity in these individuals when assessed objectively by combined heart rate and accelerometry monitor (Actiheart). Methods and Results— Participants wore the Actiheart for ⩽7 days on 2 occasions after a maximal exercise test that was used to calibrate the monitor individually against intensity levels. Of 16 participants, 13 (81%) had long QT syndrome, 9 (56%) were female, and median age was 12 years. Monitors were worn for a median (range) of 13 (6–14) days, and a mean (SD) of 11.3 (1.7) hours per day. Vigorous (7 MET) and very vigorous (10 MET) thresholds were exceeded by 15 and 13 participants, respectively. The median (interquartile range), individual, total weekly time spent >7 MET threshold was 113 (65–330) minutes, whereas such time spent >10 MET threshold was 53 (9–115) minutes. Total time >7 MET threshold was 2.3% of monitor wear time. There were no differences in time above threshold between male and female participants (P=0.357) or among those with different levels of activity restriction (P=0.769). Conclusions— Current recommended activity guidelines are frequently exceeded during routine free-living activities in young participants with inherited arrhythmia syndromes. Whether this indicates increased risk for these individuals or excessively restrictive guidelines remains to be determined.

Whole exome sequencing identifies the TNNI3K gene as a cause of familial conduction system disease and congenital junctional ectopic tachycardia

Whole exome sequencing identifies the TNNI3K gene as a cause of familial conduction system disease and congenital junctional ectopic tachycardia☆ Yanwei Xi , Christina Honeywell , Dapeng Zhang , Jeremy Schwartzentruber , Chandree L. Beaulieu , Martine Tetreault , Taila Hartley , Jennifer Marton , Silvia M. Vidal , Jacek Majewski , L. Aravind , Care4Rare Canada Consortium, Michael Gollob , Kym M. Boycott ⁎, Robert M. Gow b,⁎⁎,1

Genetic Counselors: An Important Resource for Families following a Young Sudden Cardiac Death

Sudden cardiac death is a tragic result of a number of cardiovascular diseases. While the majority of sudden cardiac death cases are in older individuals with coronary artery disease, victims also include younger people (those less than 40 years old). At least 40% of cases of young sudden death are attributable to genetic causes, including diagnoses such as long QT syndrome and hypertrophic cardiomyopathy. In 50% of young sudden death cases, there are no warning signs or family history of sudden death. These young sudden deaths are a tragedy for families and in many cases are devastating for communities as well. Awareness is spreading among medical examiners and cardiologists on how to assess and treat these families but few healthcare providers see cases routinely. The combination of an unexpected death and the burden of potentially having a genetic disease themselves leaves family members in a vulnerable and often overwhelming position. Genetic counselors, particularly those who specialize in cardiovascular disease, are uniquely qualified to help surviving family members navigate the medical and psychosocial issues present in these cases.

Peer Observed Interaction and Structured Evaluation (POISE): A Canadian Experience with Peer Supervision for Genetic Counselors

Peer observation, while often used in other professions, has not been formally applied in genetic counseling. The objective of this study was to pilot a method of peer evaluation whereby genetic counselors observed, and were observed by, each other during patient interaction. All of the available genetic counselors participated in both rounds of the pilot study (six in round one, seven in round two). The genetic counselors that observed the session used an observation room. Most participants reported learning a new skill. Sensitivity to, and comfort with, the feedback process improved. We conclude that Peer-Observed Interaction and Structured Evaluation (POISE) provides an opportunity to refresh counseling approaches and develop feedback skills without causing undue team discord. This new approach to peer supervision in genetic counselling offers a live observation approach for genetic counsellor supervision.

Array CGH ends diagnostic odyssey for infant with features of Williams and Alagille syndrome.

Array CGH Ends Diagnostic Odyssey for Infant With Features of Williams and Alagille Syndrome C. Honeywell,* L. Gardin, C. Jimenez-Rivera, and J. Allanson Department of Genetics, Children’s Hospital of Eastern Ontario, Ontario, Canada Department of Cardiology, Children’s Hospital of Eastern Ontario, Ontario, Canada Department of Gastroenterology, Children’s Hospital of Eastern Ontario, Ontario, Canada

Molecular autopsy in the sudden cardiac death of a young woman: A first Canadian report

Standard autopsy of young victims with sudden cardiac death commonly does not identify a specific pathological diagnosis. In such cases, sudden cardiac death may be secondary to a genetic condition predisposing the patient to ventricular arrhythmias. Failure to identify a genetic etiology for an unexpected sudden death may leave surviving family members at risk for a similar tragedy. The case of a 21-year-old woman who died suddenly while at rest is presented. Molecular genetic analysis of tissue retrieved from the regional coroners office identified a novel missense mutation in the KCNH2 gene, a gene known to cause the long QT syndrome.