KCNQ1 V141M and Short QT Syndrome: are we dealing with a different entity?

Abstract   Short QT Syndrome (SQTS) is a highly malignant inherited primary electrical disease that is associated with ventricular arrhythmias and sudden cardiac death (SCD); despite this, some patients may present a different arrhythmic phenotype with supraventricular affection. One particular presentation can be notably separated from others. The V141M variant from the KCNQ1 gene frequently presents with fetal bradycardia, atrial fibrillation, sinus, and AV node dysfunction, but without a single reported event of ventricular arrhythmia. To perform a literature review and pool analysis of SQTS cases, and compare patients with the V141M mutation in KCNQ1 to other SQTS cases to determine if we are dealing with a different electrical disorder. We conducted a search in the Varsome, Mastermind, MEDLINE, PubMed, and ClinVar databases to identify SQTS patients and conduct a pooled analysis. Their age, gender, clinical presentation, ECG findings, genetic analysis, and follow-up assessment were collected for analysis. If the duration of the QT interval was not described, it was determined by direct measurements in published ECG. For the comparison between groups, SQTS patients, we separated into two main groups: Non-KCNQ1 V141M patients (Group 1) and positive KCNQ1 V141M mutation (Group 2). Categorical variables are expressed as percentages. The categorical variables were analyzed using chi-square or Fisher exact test when necessary. We gathered 56 patients with a diagnosis of SQTS from 27 previous publications combined with one other case followed by the authors. A total of 13 (23.2%) patients presented with the V141M KCNQ1 mutation, the majority of KCNQ1 V141M patients were female (10 [77%]). Patients from group 1 had a significantly higher rate of familiar SCD (53.4% vs. 18.1%; P=0.04). Patients from the latter group have a significant history of SND when compared to the control group (36.3% vs. 0; P=0.001). The presence of SCD showed no significant difference between the two groups; nevertheless, the difference regarding ventricular arrhythmias is well represented (41.8% vs. 0; P=0.01). Both sinus and AV node dysfunction were present in almost all V141M patients when compared to the control group; a statistical significance was found (P = >0.001 for both instances). On the same regard, almost all patients from de V141M group presented SVA (84.6% vs 28.5%; P=0.001), specifically atrial fibrillation was present in all but 2 patients from the V141M group, which was significant (84.6% vs 24.3%; P = >0.001). Finally, fetal bradycardia was present in most of the members of this group, in contrast with the control group, with no patients with this characteristic (P = >0.001). SQTS is a phenotypically heterogeneous disease with many genetic subtypes; we propose a differentiation between the common known presentations of this syndrome and the more defined phenotype of the KCNQ1 V141M mutation. First Mexican patient with SQTS Funding Acknowledgement Type of funding source: None