Short Qt Syndrome 2

A number sign (#) is used with this entry because of evidence that short QT syndrome-2 (SQT2) is caused by heterozygous mutation in the KCNQ1 gene (607542) on chromosome 11p15.

Description

Short QT syndrome is a cardiac channelopathy associated with a predisposition to atrial fibrillation and sudden cardiac death. Patients have a structurally normal heart, but electrocardiography (ECG) exhibits abbreviated QTc (Bazett's corrected QT) intervals of less than 360 ms (summary by Moreno et al., 2015).

For a discussion of genetic heterogeneity of short QT syndrome, see SQT1 (609620).

Clinical Features

Bellocq et al. (2004) reported a 70-year-old man who was successfully resuscitated after an episode of ventricular fibrillation. A short QT interval on a subsequent ECG (290 ms) and on every ECG through 3 years of follow-up was noted. He had no prior symptoms and no other physical or physiologic abnormalities, and his family history was unremarkable.

Hong et al. (2005) studied a female infant who was delivered at 28 weeks of gestation due to fetal bradycardia and irregular rhythm. At birth she had a normal physical exam apart from bradycardia at 60 beats per minute (bpm). ECG showed atrial fibrillation (AF) with slow ventricular response and short QT interval (280 ms). Electrical cardioversion did not terminate the AF. At follow-up her heart was growing normally and she remained asymptomatic, although ECG showed conduction block with ventricular escape rhythms. Family evaluation was negative except for a great-grandparent who developed AF at an advanced age, and thus it was not considered to represent familial AF.

Villafane et al. (2014) reported 2 girls with short QT intervals, AF, and bradycardia. The first was a 6.5-year-old girl who presented at birth with AF and a ventricular rate of 60 bpm, who was diagnosed with SQT at 4 months of age (QTc, 292 ms). She underwent placement of a ventricular pacemaker at age 6 days due to persistent marked bradycardia. Electrophysiologic testing showed coexisting sinus and AV node dysfunction. The second patient was a 9-year-old girl who was diagnosed with fetal bradycardia (55 bpm) at 24 weeks of gestation. At birth, AF was documented, with a QTc of 317 ms. Holter monitoring at 11 months of age showed AF with a slow ventricular response at 35 to 70 bpm. AF was refractory to DC cardioversion and multiple antiarrhythmic agents in both patients. Both were clinically asymptomatic and neither had structural heart disease.

Moreno et al. (2015) studied a 23-year-old man whose father died unexpectedly at age 37 years while working as a postman. The son, who was healthy and athletic, showed sinus bradycardia on ECG with a slightly shortened QTc interval of 356 ms. On exercise testing, his QTc shortened further, to 350 ms at maximum workload. Echocardiography and cardiac MRI revealed a normal heart, and no arrhythmias were detected on 24-hour Holter monitoring.

Molecular Genetics

In a 70-year-old man with short QT syndrome who survived an episode of ventricular fibrillation, Bellocq et al. (2004) identified a missense mutation in the KCNQ1 gene (V307L; 607542.0037).

In a female infant with a short QT interval, AF, and bradycardia, Hong et al. (2005) analyzed the KCNQ1 gene and identified heterozygosity for a de novo missense mutation (V141M; 607542.0045). Functional analysis in Xenopus oocytes indicated that the mutant channels were constitutively open.

In 2 unrelated girls with short QT intervals, AF, and bradycardia, Villafane et al. (2014) identified heterozygosity for the V141M mutation in the KCNQ1 gene.

In a 23-year-old man with a slightly shortened QT interval, who was negative for mutation in 6 channelopathy-associated genes, Moreno et al. (2015) identified heterozygosity for a missense mutation in the KCNQ1 gene (F279I; 607542.0046). The mutation was not found in his unaffected sister or mother; DNA was unavailable from his father, who had died unexpectedly at age 37 years.

Reviews

Schimpf et al. (2005) reviewed the clinical, electrophysiologic, and molecular features of 15 reported cases and 2 unpublished cases of short QT syndrome types 1, 2, and 3 (609622).