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Diamant, Ulla-Britt
Publications (10 of 14) Show all publications
Nilsson, U., Kanerud, I., Diamant, U.-B., Blomberg, A., Eriksson, B. & Lindberg, A. (2019). The prevalence of prolonged QTc increases by GOLD stage, and is associated with worse survival among subjects with COPD. Heart & Lung, 48(2), 148-154
Open this publication in new window or tab >>The prevalence of prolonged QTc increases by GOLD stage, and is associated with worse survival among subjects with COPD
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2019 (English)In: Heart & Lung, ISSN 0147-9563, E-ISSN 1527-3288, Vol. 48, no 2, p. 148-154Article in journal (Refereed) Published
Abstract [en]

Background: The role of QTc-prolongation, in relation to the increased mortality in COPD, is unclear.

Objectives: To estimate the prevalence and prognostic impact, assessed as mortality, of QTc-prolongation in COPD, restrictive spirometric pattern (RSP), and normal lung function (NLF), respectively.

Methods: All individuals (n = 993) with COPD and age- and sex-matched non-obstructive referents were identified from well-defined population-based cohorts examined in Northern Sweden in 2002–04. In 2005, the study-sample was invited to re-examination including ECG; QTc was calculated and mortality data collected until 31st December 2010.

Results: The prevalence of QTc-prolongation was higher among people with RSP than among those with NLF and, although similar in NLF and COPD, the prevalence increased by COPD-severity. Among participants with COPD, those with QTc prolongation had higher mortality than those with normal QTc, while no such differences were found among participants with NLF or RSP.

Conclusion: Among participants with COPD, the prevalence of QTc-prolongation increased by disease-severity and was associated with mortality.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Epidemiology, Comorbidity, Cardiology, Electrocardiogram, Pulmonary disease, Chronic obstructive
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-158114 (URN)10.1016/j.hrtlng.2018.09.015 (DOI)000462808300013 ()30391074 (PubMedID)
Funder
Swedish Heart Lung Foundation
Available from: 2019-04-12 Created: 2019-04-12 Last updated: 2019-04-12Bibliographically approved
Sundström, E., Jensen, S. M., Diamant, U.-B. & Rydberg, A. (2017). Implantable cardioverter defibrillator treatment in long QT syndrome patients: a national study on adherence to international guidelines. Scandinavian Cardiovascular Journal, 51(2), 88-94
Open this publication in new window or tab >>Implantable cardioverter defibrillator treatment in long QT syndrome patients: a national study on adherence to international guidelines
2017 (English)In: Scandinavian Cardiovascular Journal, ISSN 1401-7431, E-ISSN 1651-2006, Vol. 51, no 2, p. 88-94Article in journal (Refereed) Published
Abstract [en]

Objectives. Implantable cardioverter defibrillator (ICD) treatment is effective among long QT syndrome (LQTS) patients at a high risk of sudden cardiac death. Previous studies show that the international guidelines are not always followed, and that risk stratification may be based on genotype rather than individual risk profile. We analysed data from the Swedish ICD & Pacemaker Registry and medical records to examine how international guidelines were followed with regards to phenotype and genotype. Methods and results. ICD treatment was used in 150 Swedish LQTS patients from 1989-2013. The annual number of implantations increased over the study period. A total of 109 patients were included in the analysis. Most patients (91%) were symptomatic before the implantation. Seventy percent of patients who received ICD treatment met the 2006 Class I or Class IIa recommendations for LQTS treatment. Thirty-one percent of the LQT3 patients received ICD treatment despite being asymptomatic. Among LQT1 patients, 45% received ICD treatment after syncope despite beta-blockers. Conclusions. Thirty percent of Swedish LQTS patients with ICD received the treatment without a strong indication based on international guidelines. LQT3 patients were over-represented among asymptomatic patients. Many LQT1 patients received ICD despite the known effect of beta-blockers in this group.

Keywords
Long QT syndrome, implantable cardioverter defibrillator, guidelines, beta-blocker treatment, orted cardiac arrest, syncope
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-133734 (URN)10.1080/14017431.2016.1270463 (DOI)000395166500005 ()27936942 (PubMedID)
Available from: 2017-05-08 Created: 2017-05-08 Last updated: 2019-05-20Bibliographically approved
Winbo, A., Fosdal, I., Lindh, M., Diamant, U.-B., Persson, J., Wettrell, G. & Rydberg, A. (2015). Third Trimester Fetal Heart Rate Predicts Phenotype and Mutation Burden in the Type 1 Long QT Syndrome. Circulation: Arrhythmia and Electrophysiology, 8(4), 806-814
Open this publication in new window or tab >>Third Trimester Fetal Heart Rate Predicts Phenotype and Mutation Burden in the Type 1 Long QT Syndrome
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2015 (English)In: Circulation: Arrhythmia and Electrophysiology, ISSN 1941-3149, E-ISSN 1941-3084, Vol. 8, no 4, p. 806-814Article in journal (Refereed) Published
Abstract [en]

Background—Early diagnosis and risk stratification is of clinical importance in the long QT syndrome (LQTS), however, little genotype-specific data are available regarding fetal LQTS. We investigate third trimester fetal heart rate, routinely recorded within public maternal health care, as a possible marker for LQT1 genotype and phenotype.

Methods and Results—This retrospective study includes 184 fetuses from 2 LQT1 founder populations segregating p.Y111C and p.R518X (74 noncarriers and 110KCNQ1 mutation carriers, whereof 13 double mutation carriers). Pedigree-based measured genotype analysis revealed significant associations between fetal heart rate, genotype, and phenotype; mean third trimester prelabor fetal heart rates obtained from obstetric records (gestational week 29–41) were lower per added mutation (no mutation, 143±5 beats per minute; single mutation, 134±8 beats per minute; double mutations, 111±6 beats per minute; P<0.0001), and lower in symptomatic versus asymptomatic mutation carriers (122±10 versus 137±9 beats per minute; P<0.0001). Strong correlations between fetal heart rate and neonatal heart rate (r=0.700; P<0.001), and postnatal QTc (r=−0.762; P<0.001) were found. In a multivariable model, fetal genotype explained the majority of variance in fetal heart rate (−10 beats per minute per added mutation; P<1.0×10–23). Arrhythmia symptoms and intrauterine β-blocker exposure each predicted −7 beats per minute, P<0.0001.

Conclusions—In this study including 184 fetuses from 2 LQT1 founder populations, third trimester fetal heart rate discriminated between fetal genotypes and correlated with severity of postnatal cardiac phenotype. This finding strengthens the role of fetal heart rate in the early detection and risk stratification of LQTS, particularly for fetuses with double mutations, at high risk of early life-threatening arrhythmias.

Keywords
arrhythmias, cardiac, genotype, genetic association studies, heart rate, long QT syndrome
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-108470 (URN)10.1161/CIRCEP.114.002552 (DOI)000359740500011 ()26019114 (PubMedID)
Available from: 2015-09-22 Created: 2015-09-11 Last updated: 2018-06-07Bibliographically approved
Winbo, A., Stattin, E.-L., Nordin, C., Diamant, U.-B., Persson, J., Jensen, S. M. & Rydberg, A. (2014). Phenotype, origin and estimated prevalence of a common long QT syndrome mutation: a clinical, genealogical and molecular genetics study including Swedish R518X/KCNQ1 families. BMC Cardiovascular Disorders, 14, 22
Open this publication in new window or tab >>Phenotype, origin and estimated prevalence of a common long QT syndrome mutation: a clinical, genealogical and molecular genetics study including Swedish R518X/KCNQ1 families
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2014 (English)In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 14, p. 22-Article in journal (Refereed) Published
Abstract [en]

Background: The R518X/KCNQ1 mutation is a common cause of autosomal recessive (Jervell and Lange Nielsen Syndrome-JLNS) and autosomal dominant long QT syndrome (LQTS) worldwide. In Sweden p.R518X accounts for the majority of JLNS cases and is the second most common cause of LQTS. Here we investigate the clinical phenotype and origin of Swedish carriers of the p. R518X mutation. Methods: The study included 19 Swedish p. R518X index families, ascertained by molecular genetics methods (101 mutation-carriers, whereof 15 JLNS cases and 86 LQTS cases). In all families analyses included assessment of clinical data (symptoms, medications and manually measured electrocardiograms), genealogy (census records), haplotype (microsatellite markers) as well as assessment of mutation age and associated prevalence (ESTIAGE and DMLE computer software). Results: Clinical phenotype ranged from expectedly severe in JLNS to surprisingly benign in LQTS (QTc 576 +/- 61 ms vs. 462 +/- 34 ms, cumulative incidence of (aborted) cardiac arrest 47% vs. 1%, annual non-medicated incidence rate (aborted) cardiac arrest 4% vs. 0.04%). A common northern origin was found for 1701/1929 ancestors born 1650-1950. Historical geographical clustering in the coastal area of the Pite River valley was shown. A shared haplotype spanning the KCNQ1 gene was seen in 17/19 families. Mutation age was estimated to 28 generations (95% CI 19;41). A high prevalence of Swedish p. R518X heterozygotes was suggested (similar to 1: 2000-4000). Conclusions: R518X/KCNQ1 occurs as a common founder mutation in Sweden and is associated with an unexpectedly benign phenotype in heterozygous carriers.

Place, publisher, year, edition, pages
BioMed Central, 2014
Keywords
Long QT Syndrome, Genotype-phenotype correlations, Clinical phenotype, Founder mutation, Mutation age, Prevalence estimate
National Category
Pediatrics
Identifiers
urn:nbn:se:umu:diva-88970 (URN)10.1186/1471-2261-14-22 (DOI)000334534000001 ()
Available from: 2014-05-26 Created: 2014-05-19 Last updated: 2018-06-07Bibliographically approved
Diamant, U.-B., Vahedi, F., Winbo, A., Rydberg, A., Stattin, E.-L., Jensen, S. M. & Bergfeldt, L. (2013). Electrophysiological phenotype in the LQTS mutations Y111C and R518X in the KCNQ1 gene. Journal of applied physiology, 115(10), 1423-1432
Open this publication in new window or tab >>Electrophysiological phenotype in the LQTS mutations Y111C and R518X in the KCNQ1 gene
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2013 (English)In: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, no 10, p. 1423-1432Article in journal (Refereed) Published
Abstract [en]

Long QT syndrome is the prototypical disorder of ventricular repolarization (VR), and a genotype-phenotype relation is postulated. Furthermore, although increased VR heterogeneity (dispersion) may be important in the arrhythmogenicity in long QT syndrome, this hypothesis has not been evaluated in humans and cannot be tested by conventional electrocardiography. In contrast, vectorcardiography allows assessment of VR heterogeneity and is more sensitive to VR alterations than electrocardiography. Therefore, vectorcardiography was used to compare the electrophysiological phenotypes of two mutations in the LQT1 gene with different in vitro biophysical properties, and with LQT2 mutation carriers and healthy control subjects. We included 99 LQT1 gene mutation carriers (57 Y111C, 42 R518X) and 19 LQT2 gene mutation carriers. Potassium channel function is in vitro most severely impaired in Y111C. The control group consisted of 121 healthy subjects. QRS, QT, and T-peak to T-end (Tp-e) intervals, measures of the QRS vector and T vector and their relationship, and T-loop morphology parameters were compared at rest. Apart from a longer heart rate-corrected QT interval (QT heart rate corrected according to Bazett) in Y111C mutation carriers, there were no significant differences between the two LQT1 mutations. No signs of increased VR heterogeneity were observed among the LQT1 and LQT2 mutation carriers. QT heart rate corrected according to Bazett and Tp-e were longer, and the Tp-e-to-QT ratio greater in LQT2 than in LQT1 and the control group. In conclusion, there was a marked discrepancy between in vitro potassium channel function and in vivo electrophysiological properties in these two LQT1 mutations. Together with previous observations of the relatively low risk for clinical events in Y111C mutation carriers, our results indicate need for cautiousness in predicting in vivo electrophysiological properties and the propensity for clinical events based on in vitro assessment of ion channel function alone.

Place, publisher, year, edition, pages
American Physiological Society, 2013
Keywords
electrocardiography, electrophysiology, long QT syndrome, diagnosis, arrhythmia, genes, mutation
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-80102 (URN)10.1152/japplphysiol.00665.2013 (DOI)000327398600002 ()24052033 (PubMedID)
Funder
Swedish Heart Lung Foundation
Available from: 2013-09-09 Created: 2013-09-09 Last updated: 2018-06-08Bibliographically approved
Vahedi, F., Diamant, U.-B., Lundahl, G., Bergqvist, G., Gransberg, L., Jensen, S. M. & Bergfeldt, L. (2013). Instability of repolarization in LQTS mutation carriers compared to healthy control subjects assessed by vectorcardiography. Heart Rhythm, 10(8), 1169-1175
Open this publication in new window or tab >>Instability of repolarization in LQTS mutation carriers compared to healthy control subjects assessed by vectorcardiography
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2013 (English)In: Heart Rhythm, ISSN 1547-5271, E-ISSN 1556-3871, Vol. 10, no 8, p. 1169-1175Article in journal (Refereed) Published
Abstract [en]

BACKGROUND Potassium channel dysfunction in congenital and acquired forms of long QT syndrome types 1 and 2 (LQT1 and LQT2) increases the beat-to-beat variability of the (IT interval. OBJECTIVE To study about the little known variability (instability) of other aspects of ventricular repolarization (VR) in humans by using vectorcardiography. METHODS Beat-to-beat analysis was performed regarding vectorcardiography derived RR, QRS, and QT intervals, as well as T vector- and T vector loop-based parameters during 1-minute recordings of uninterrupted sinus rhythm at rest in 41 adult LQT1 (n = 31) and LQT2 (n = 10) mutation carriers and 41 age- and sex-matched control subjects. The short-term variability for each parameter, describing the mean orthogonal distance to the line of identity on the Poincare plot, was calculated. RESULTS Mutation carriers showed significantly larger (by a factor 2) instability in most VR parameters compared to controls despite higher instantaneous heart rate variability (STVRR) in the control group. The longer the (IT interval, the greater was its instability, and the instability of VR dispersion measures. CONCLUSIONS A greater instability of most aspects of VR already at rest seems to be a salient feature in both LQT1 and LQT2, which might pave the way for early afterdepolarizations and torsades de pointes ventricular tachycardia. In contrast, no signs of increased VR dispersion per se were observed in mutation carriers.

Keywords
Long QT syndrome, Repolarization, Short-term variability, Vectorcardiography, the amplitude of the maximum T vector in space, T peak to T end, the last part of the QT interval and final repolarization in the 3-dimensional QRST complex
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-80441 (URN)10.1016/j.hrthm.2013.05.001 (DOI)000323492700014 ()
Available from: 2014-02-21 Created: 2013-09-17 Last updated: 2018-06-08Bibliographically approved
Diamant, U.-B. (2013). Long QT syndrome: studies of diagnostic methods. (Doctoral dissertation). Umeå: Umeå universitet
Open this publication in new window or tab >>Long QT syndrome: studies of diagnostic methods
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: The Long QT Syndrome (LQTS) is a hereditary heart disease with risk of malignant ventricular arrhythmia and sudden cardiac death. Despite our increased knowledge about genotype and phenotype correlation we still rely on the 12-lead ECG for assessment of the QT interval and the T-wave morphology for diagnosis and risk stratification. Intra- and -inter individual variability in manually QT measurement and, e.g., difficulties in defining the end of the T-wave may impair the diagnosis of LQTS. Increased heterogeneity in ventricular repolarization (VR) may be an important factor in the arrhythmogenicity in cases of LQTS. In a LQTS founder population the same mutation is carried by numerous individuals in many families which provide a unique opportunity to study diagnostic methods, risk assessment, VR and the correlation between genotype and phenotype.

Methods: Resting 12-lead ECG and vectorcardiogram (VCG) were recorded in 134 LQTS mutation carriers and 121 healthy controls, to investigate the capability and precision in measuring the QT interval. For assessment of the VR, VCG was compared in individuals with mutations in the KCNQ1 and KCNH2 gene. Genealogical and geographic studies were performed in 37 index cases and their relatives to determine if Swedish carriers of the Y111C mutation in the KCNQ1 gene constitute a founder population. To confirm kinship, haplotype analysis was performed in 26 of the 37 index cases. The age and prevalence of the Y111C mutation were calculated in families sharing a common haplotype.

Results: VCG by automatic measurement of the QT interval provided the best combination of sensitivity (90%) and specificity (89%) in the diagnosis of LQTS. VCG showed no consistent pattern of increased VR heterogeneity among KCNQ1 and KCNH2 mutation carriers. Living carriers of the Y111C mutation shared a common genetic (haplotype), genealogic and geographic origin. The age of the Y111C mutation was approximately 600 years. The prevalence of living carriers of the Y111C mutation in the mid-northern Sweden was estimated to 1:1,500-3,000.

Conclusion: We have shown that VCG provides a valuable contribution to the diagnosis and risk assessment of LQTS in adults and children. No consistent pattern of increased VR heterogeneity was found among the LQTS mutation carriers. The identified Swedish LQTS founder population will be a valuable source to future LQTS research and may contribute to increase our understanding of LQTS and the correlation of phenotype, genotype and modifying factors.

Place, publisher, year, edition, pages
Umeå: Umeå universitet, 2013. p. 67
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1583
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-80103 (URN)978-91-7459-693-9 (ISBN)
Public defence
2013-10-04, Hörsal D, Unod T 9, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-09-12 Created: 2013-09-09 Last updated: 2018-06-08Bibliographically approved
Diamant, U.-B., Jensen, S. M., Winbo, A., Stattin, E.-L. & Rydberg, A. (2013). Vectorcardiographic recordings of the Q-T interval in a pediatric long Q-T syndrome population. Pediatric Cardiology, 34(2), 245-249
Open this publication in new window or tab >>Vectorcardiographic recordings of the Q-T interval in a pediatric long Q-T syndrome population
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2013 (English)In: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 34, no 2, p. 245-249Article in journal (Refereed) Published
Abstract [en]

Measurements of the Q-T interval are less reliable in children than in adults. Identification of superior diagnostic tools is warranted. This study aimed to investigate whether a vectorcardiogram (VCG) recorded from three orthogonal leads (X, Y, Z) according to Frank is superior to a 12-lead electrocardiogram (ECG) in providing a correct long Q-T syndrome (LQTS) diagnosis in children. This LQTS group consisted of 35 genetically confirmed carriers of mutations in the KCNQ1 (n = 29) and KCNH2 (n = 6) genes. The control group consisted of 35 age- and gender-matched healthy children. The mean age was 7 years in the LQTS group and 6.7 years in the control group (range, 0.5-16 years). The corrected Q-T interval (QT(c)) was measured manually (QT(man)) by one author (A.W.). The 12-lead ECG automatic measurements (QT(ECG)) and interpretation (QT(Interpret)) of QT(c) were performed with the Mac5000 (GE Medical System), and the VCG automatic measurements (QT(VCG)) were performed with the Mida1000, CoroNet (Ortivus AB, Sweden). By either method, a QT(c) longer than 440 ms was considered prolonged and indicative of LQTS. Of the 35 children with genetically confirmed LQTS, 30 (86 %) received a correct diagnosis using QT(VCG), 29 (82 %) using QT(man), 24 (69 %) using QT(ECG), and 17 (49 %) using QT(Interpret). Specificity was 0.80 for QT(VCG), 0.83 for QT(man), 0.77 for QT(ECG), and 0.83 for QT(Interpret). The VCG automatic measurement of QT(c) seems to be a better predictor of LQTS than automatic measurement and interpretation of 12-lead ECG.

Keywords
Children, Electrocardiogram, Long QT syndrome, QT, Vectorcardiogram
National Category
Cardiac and Cardiovascular Systems Pediatrics
Identifiers
urn:nbn:se:umu:diva-67401 (URN)10.1007/s00246-012-0425-2 (DOI)000315036500007 ()
Available from: 2013-04-09 Created: 2013-03-18 Last updated: 2018-06-08Bibliographically approved
Stattin, E.-L., Boström, I. M., Winbo, A., Cederquist, K., Jonasson, J., Jonsson, B.-A., . . . Norberg, A. (2012). Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing. BMC Cardiovascular Disorders, 12, 95
Open this publication in new window or tab >>Founder mutations characterise the mutation panorama in 200 Swedish index cases referred for Long QT syndrome genetic testing
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2012 (English)In: BMC Cardiovascular Disorders, ISSN 1471-2261, E-ISSN 1471-2261, Vol. 12, p. 95-Article in journal (Refereed) Published
Abstract [en]

Background: Long QT syndrome (LQTS) is an inherited arrhythmic disorder characterised by prolongation of the QT interval on ECG, presence of syncope and sudden death. The symptoms in LQTS patients are highly variable, and genotype influences the clinical course. This study aims to report the spectrum of LQTS mutations in a Swedish cohort.

Methods: Between March 2006 and October 2009, two hundred, unrelated index cases were referred to the Department of Clinical Genetics, Umea University Hospital, Sweden, for LQTS genetic testing. We scanned five of the LQTS-susceptibility genes (KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2) for mutations by DHPLC and/or sequencing. We applied MLPA to detect large deletions or duplications in the KCNQ1, KCNH2, SCN5A, KCNE1, and KCNE2 genes. Furthermore, the gene RYR2 was screened in 36 selected LQTS genotype-negative patients to detect cases with the clinically overlapping disease catecholaminergic polymorphic ventricular tachycardia (CPVT).

Results: In total, a disease-causing mutation was identified in 103 of the 200 (52%) index cases. Of these, altered exon copy numbers in the KCNH2 gene accounted for 2% of the mutations, whereas a RYR2 mutation accounted for 3% of the mutations. The genotype-positive cases stemmed from 64 distinct mutations, of which 28% were novel to this cohort. The majority of the distinct mutations were found in a single case (80%), whereas 20% of the mutations were observed more than once. Two founder mutations, KCNQ1 p.Y111C and KCNQ1 p.R518*, accounted for 25% of the genotype-positive index cases. Genetic cascade screening of 481 relatives to the 103 index cases with an identified mutation revealed 41% mutation carriers who were at risk of cardiac events such as syncope or sudden unexpected death.

Conclusion: In this cohort of Swedish index cases with suspected LQTS, a disease-causing mutation was identified in 52% of the referred patients. Copy number variations explained 2% of the mutations and 3 of 36 selected cases (8%) harboured a mutation in the RYR2 gene. The mutation panorama is characterised by founder mutations (25%), even so, this cohort increases the amount of known LQTS-associated mutations, as approximately one-third (28%) of the detected mutations were unique.

Place, publisher, year, edition, pages
BioMed Central, 2012
Keywords
Arrhythmia, Long QT syndrome, Ion-channel, Founder mutation, Variant of unknown significance
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-64060 (URN)10.1186/1471-2261-12-95 (DOI)000312312500001 ()
Available from: 2013-01-15 Created: 2013-01-14 Last updated: 2018-06-08Bibliographically approved
Winbo, A., Stattin, E.-L., Diamant, U.-B., Persson, J., Jensen, S. M. & Rydberg, A. (2012). Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden. Europace, 14(12), 1799-1806
Open this publication in new window or tab >>Prevalence, mutation spectrum, and cardiac phenotype of the Jervell and Lange-Nielsen syndrome in Sweden
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2012 (English)In: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 14, no 12, p. 1799-1806Article in journal (Refereed) Published
Abstract [en]

AIMS: To explore the national prevalence, mutation spectrum, cardiac phenotype, and outcome of the uncommon Jervell and Lange-Nielsen syndrome (JLNS), associated with a high risk of sudden cardiac death.

METHODS AND RESULTS: A national inventory of clinical JLNS cases was performed. Genotype and area of origin were ascertained in index families. Retrospective clinical data were collected from medical records and interviews. We identified 19 cases in 13 Swedish families. A JLNS prevalence >1:200 000 was revealed (five living cases <10 years of age). The mutation spectrum consisted of eight KCNQ1 mutations, whereof p.R518X in 12/24 alleles. Geographic clustering of four mutations (20/24 alleles) and similarities to Norway's mutation spectrum were seen. A high prevalence of heterozygotes was suggested. Three paediatric cases on β-blockers since birth were as yet asymptomatic. Seven symptomatic cases had suffered an aborted cardiac arrest and four had died suddenly. QTc prolongation was significantly longer in symptomatic cases (mean 605 ± 62 vs. 518 ± 50 ms, P = 0.016). β-Blockers reduced, but did not abolish, cardiac events in any previously symptomatic case. β-Blocker type, dosage, and compliance probably affect outcome significantly. Implantable cardioverter-defibrillator therapy (ICD, n = 6) was associated with certain complications; however, no case of sudden death.

CONCLUSION: Founder effects could explain 83% of the Swedish JLNS mutation spectrum and probably contribute to the high JLNS prevalence found in preadolescent Swedish children. Due to the severe cardiac phenotype in JLNS, the importance of stringent β-blocker therapy and compliance, and consideration of ICD implantation in the case of therapy failure is stressed.

Keywords
Jervell and Lange-Nielsen syndrome, Founder effects, KCNQ1 gene, Cardiac phenotype, Therapy efficacy
National Category
Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-56903 (URN)10.1093/europace/eus111 (DOI)22539601 (PubMedID)
Available from: 2012-06-28 Created: 2012-06-28 Last updated: 2018-06-08Bibliographically approved
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