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postgraduate thesis: Genetic counseling in sudden arrhythmia death syndrome : the science and the art

TitleGenetic counseling in sudden arrhythmia death syndrome : the science and the art
Authors
Issue Date2013
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Liu, P. A. [廖柏賢]. (2013). Genetic counseling in sudden arrhythmia death syndrome : the science and the art. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5137425
AbstractBackground: Sudden arrhythmia death syndrome (SADS) is a genotypically and phenotypically heterogeneous condition that might produce fatal ventricular arrhythmia in otherwise healthy individuals. Congenital long QT syndrome (LQTS) is the most common type of SADS with a frequency of 1 in 2500 individuals. Up to 13 genes have been shown to be associated with LQTS and genetic testing has a role in disease diagnosis, prognostication, treatment guidance, cascade testing, and reproductive counseling. Interdisciplinary care is the standard but such service is unavailable in Hong Kong. Objectives: In this study, we aim to evaluate the clinical characteristics of a local cohort of pediatric patients with LQTS, establish the practicability of a model on interdisciplinary delivery of care for SADS, and explore the process of genetic counseling in Chinese families with LQTS from the perspective of discourse analysis. Method: Pediatric patients with LQTS and their families were recruited from the Department of Paediatric Cardiology, Queen Mary Hospital between 1 January 2011 and 31 December 2012. With informed consent, patients underwent genetic testing for 6 LQTS genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2). Clinical characteristics were documented and the process of pre-test and post-test counseling was videotaped and transcribed. Data was mapped and analyzed for discourse strategies in the focal themes of uncertainty management in risk communication. Results: 19 patients were identified, 9 were male, with the corrected QT interval (QTc) ranging from 460-619ms. Mode of presentation included syncope (n=9), ventricular tachycardia (n=2), convulsion (n=1) and as incidental finding (n=7). Pathogenic mutations were identified in 9 patients (LQT1=3, LQT2=4, LQT3=1, LQT5=1), likely pathogenic mutations in 2 (LQT2), unclassified variants in 2, and no mutation in 6. Patients with pathogenic and likely pathogenic mutations had significantly longer mean QTc than those without such mutations (p=0.046). Three mutations, all in the LQT2 genes, represented novel mutations. All 3 patients with mutations in the pore-looping forming domains of the KCNH2 (LQT2) channel had personal or family histories of malignant arrhythmia or sudden cardiac death compatible with previously reported genotype-phenotype correlation. Eight families involving 18 family members underwent cascade testing, and family mutations were identified in 10 individuals from 6 families. Autosomal dominant transmission was the likely mode of inheritance in these 6 families. Counseling sessions involved the joint input from clinical geneticist, genetic counsellor and pediatric cardiologist. Discourse analysis on 2 counseling sessions of a selected family with unclassified variants revealed increased uncertainty after genetic testing in the index patient and family members. Strategies used to mitigate uncertainty included abstraction, generalization and categorization. Conclusion: Genetic testing was crucial in the comprehensive assessment of patients with congenital LQTS, and we demonstrated a feasible model to delivery interdisciplinary care for patients with SADS in Hong Kong. The process of genetic counseling is highly complex and deserves further examination.
DegreeMaster of Medical Sciences
SubjectArrhythmia - Genetic aspects
Dept/ProgramPaediatrics and Adolescent Medicine
Persistent Identifierhttp://hdl.handle.net/10722/196059

 

DC FieldValueLanguage
dc.contributor.authorLiu, Pak-yin, Anthony-
dc.contributor.author廖柏賢-
dc.date.accessioned2014-03-24T23:12:30Z-
dc.date.available2014-03-24T23:12:30Z-
dc.date.issued2013-
dc.identifier.citationLiu, P. A. [廖柏賢]. (2013). Genetic counseling in sudden arrhythmia death syndrome : the science and the art. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5137425-
dc.identifier.urihttp://hdl.handle.net/10722/196059-
dc.description.abstractBackground: Sudden arrhythmia death syndrome (SADS) is a genotypically and phenotypically heterogeneous condition that might produce fatal ventricular arrhythmia in otherwise healthy individuals. Congenital long QT syndrome (LQTS) is the most common type of SADS with a frequency of 1 in 2500 individuals. Up to 13 genes have been shown to be associated with LQTS and genetic testing has a role in disease diagnosis, prognostication, treatment guidance, cascade testing, and reproductive counseling. Interdisciplinary care is the standard but such service is unavailable in Hong Kong. Objectives: In this study, we aim to evaluate the clinical characteristics of a local cohort of pediatric patients with LQTS, establish the practicability of a model on interdisciplinary delivery of care for SADS, and explore the process of genetic counseling in Chinese families with LQTS from the perspective of discourse analysis. Method: Pediatric patients with LQTS and their families were recruited from the Department of Paediatric Cardiology, Queen Mary Hospital between 1 January 2011 and 31 December 2012. With informed consent, patients underwent genetic testing for 6 LQTS genes (KCNQ1, KCNH2, SCN5A, KCNE1, KCNE2, KCNJ2). Clinical characteristics were documented and the process of pre-test and post-test counseling was videotaped and transcribed. Data was mapped and analyzed for discourse strategies in the focal themes of uncertainty management in risk communication. Results: 19 patients were identified, 9 were male, with the corrected QT interval (QTc) ranging from 460-619ms. Mode of presentation included syncope (n=9), ventricular tachycardia (n=2), convulsion (n=1) and as incidental finding (n=7). Pathogenic mutations were identified in 9 patients (LQT1=3, LQT2=4, LQT3=1, LQT5=1), likely pathogenic mutations in 2 (LQT2), unclassified variants in 2, and no mutation in 6. Patients with pathogenic and likely pathogenic mutations had significantly longer mean QTc than those without such mutations (p=0.046). Three mutations, all in the LQT2 genes, represented novel mutations. All 3 patients with mutations in the pore-looping forming domains of the KCNH2 (LQT2) channel had personal or family histories of malignant arrhythmia or sudden cardiac death compatible with previously reported genotype-phenotype correlation. Eight families involving 18 family members underwent cascade testing, and family mutations were identified in 10 individuals from 6 families. Autosomal dominant transmission was the likely mode of inheritance in these 6 families. Counseling sessions involved the joint input from clinical geneticist, genetic counsellor and pediatric cardiologist. Discourse analysis on 2 counseling sessions of a selected family with unclassified variants revealed increased uncertainty after genetic testing in the index patient and family members. Strategies used to mitigate uncertainty included abstraction, generalization and categorization. Conclusion: Genetic testing was crucial in the comprehensive assessment of patients with congenital LQTS, and we demonstrated a feasible model to delivery interdisciplinary care for patients with SADS in Hong Kong. The process of genetic counseling is highly complex and deserves further examination.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.subject.lcshArrhythmia - Genetic aspects-
dc.titleGenetic counseling in sudden arrhythmia death syndrome : the science and the art-
dc.typePG_Thesis-
dc.identifier.hkulb5137425-
dc.description.thesisnameMaster of Medical Sciences-
dc.description.thesislevelMaster-
dc.description.thesisdisciplinePaediatrics and Adolescent Medicine-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5137425-

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