Arrhythmias & electrophysiology
An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition
Authors' conclusion
The present study suggests that putative/confirmed loss-of-function KCNE1 variants predispose to QT prolongation, however, the low ECG penetrance observed suggests they do not manifest clinically in the majority of individuals, aligning with the mild phenotype observed for Type 2 Jervell and Lange-Nielsen syndrome patients.
Study context
- Population
- Patients with rare KCNE1 variants: presumed autosomal dominant LQT5 or recessive Type 2 Jervell and Lange-Nielsen syndrome32 distinct KCNE1 variants
- Participants
- 89 / 140 / 19
- Exposure
- Probands vs Family members vs Type 2 Jervell and Lange-Nielsen syndrome
- Probandsn = 89
- Family membersn = 140reference
- Type 2 Jervell and Lange-Nielsen syndromen = 19
- Outcome
- Definite arrhythmic events:
- Appropriate ICD shocks
- Aborted cardiac arrest
- SCD
Methodological detailsinternational, 22 genetic arrhythmia clinics and 4 registries from 9 countries
- International
- 22 genetic arrhythmia clinics and 4 registries from 9 countries
Main finding
As reported in the abstract
Definite arrhythmic events
Estimate (95% CI)P value
Probands vs Family members
adjusted HR 11.6(2.6–52.2)
P = 0.001Type 2 JLNS vs overall heterozygous cohortdid not differ significantly
HR 1.7(0.3–10.8)
P = 0.590Observational data: associations, not effects.
Further findings
Mean, ms
| Outcome | Probands | Family members | Type 2 Jervell and Lange-Nielsen syndrome | P value | |
|---|---|---|---|---|---|
| QTc on presenting ECG (presumed LQT5) | 476.9 (SD 38.6) | 441.8 (SD 30.9) | Not reported in the abstract | P < 0.001 | Type 2 Jervell and Lange-Nielsen syndrome: not reported in the abstract |
- ECG penetrance (QTc >460 ms), heterozygous family members
- 20.7% · 29 of 140
Cumulative prevalence of the 32 KCNE1 variants in gnomAD vs anticipated LQT5 prevalence
- 238-fold greater (0.238% vs 0.001%)
Original publication
An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition. Circulation. Published 16 January 2020. doi:10.
Summarised from the published abstract; every number is checked against it