| Title: |
An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition |
| Authors: |
Roberts, JD; Asaki, SY; Mazzanti, A; Bos, JM; Tuleta, I; Muir, AR; Crotti, L; Krahn, AD; Kutyifa, V; Shoemaker, MB; Johnsrude, CL; Aiba, T; Marcondes, L; Baban, A; Udupa, S; Dechert, B; Fischbach, P; Knight, LM; Vittinghoff, E; Kukavica, D; Stallmeyer, B; Giudicessi, JR; Spazzolini, C; Shimamoto, K; Tadros, R; Cadrin-Tourigny, J; Duff, HJ; Simpson, CS; Roston, TM; Wijeyeratne, YD; El Hajjaji, I; Yousif, MD; Gula, LJ; Leong-Sit, P; Chavali, N; Landstrom, AP; Marcus, GM; Dittmann, S; Wilde, AAM; Behr, ER; Tfelt-Hansen, J; Scheinman, MM; Perez, MV; Kaski, JP; Gow, RM; Drago, F; Aziz, PF; Abrams, DJ; Gollob, MH; Skinner, JR; Shimizu, W; Kaufman, ES; Roden, DM; Zareba, W; Schwartz, PJ; Schulze-Bahr, E; Etheridge, SP; Priori, SG; Ackerman, MJ |
| Source: |
Circulation , 141 (6) pp. 429-439. (2020) |
| Publication Year: |
2020 |
| Collection: |
University College London: UCL Discovery |
| Subject Terms: |
Arrhythmia; genetics; long QT syndrome; penetrance; sudden cardiac death |
| Description: |
BACKGROUND: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare KCNE1 variants implicated in LQT5 was sought through an international multicenter collaboration. METHODS: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries. KCNE1 variants were evaluated for ECG penetrance (defined as QTc >460 ms on presenting ECG) and genotype-phenotype segregation. Multivariable Cox regression was used to compare the associations between clinical and genetic variables with a composite primary outcome of definite arrhythmic events, including appropriate implantable cardioverter-defibrillator shocks, aborted cardiac arrest, and sudden cardiac death. RESULTS: A total of 32 distinct KCNE1 rare variants were identified in 89 probands and 140 genotype positive family members with presumed LQT5 and an additional 19 Type 2 Jervell and Lange-Nielsen syndrome patients. Among presumed LQT5 patients, the mean QTc on presenting ECG was significantly longer in probands (476.9±38.6 ms) compared with genotype positive family members (441.8±30.9 ms, P |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| Relation: |
https://discovery.ucl.ac.uk/id/eprint/10095403/3/Kaski_LQT5_Manuscript_Revised_Sept27.pdf; https://discovery.ucl.ac.uk/id/eprint/10095403/ |
| Availability: |
https://discovery.ucl.ac.uk/id/eprint/10095403/3/Kaski_LQT5_Manuscript_Revised_Sept27.pdf; https://discovery.ucl.ac.uk/id/eprint/10095403/ |
| Rights: |
open |
| Accession Number: |
edsbas.FA13DC8E |
| Database: |
BASE |