Short Qt Syndrome 3
A number sign (#) is used with this entry because of evidence that short QT syndrome-3 (SQT3) is caused by heterozygous mutation in the KCNJ2 gene (600681) on chromosome 17q24.
DescriptionShort 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 FeaturesPriori et al. (2005) reported an asymptomatic 5-year-old girl who was found to have an abnormal ECG on routine clinical evaluation, with a markedly short repolarization time and conspicuously narrow and peaked T waves (QTc interval, 315 ms). Investigation of the family revealed that her 35-year-old father had a short QT interval (320 ms) and a history of presyncopal episodes and palpitations since age 15. ECGs of the proband and her father were characterized by asymmetric T waves with a fairly normal ascending phase and a remarkably rapid terminal phase, a pattern that was consistently present and could be seen in the first ECG of the father at age 15. The mother and the paternal grandparents had unremarkable ECGs and reported no family histories of sudden death.
Molecular GeneticsIn a 5-year-old girl and her father who had short QT intervals and asymmetric T waves on ECG and who were negative for mutations in the 2 genes previously associated with short QT syndrome, KCNH2 and KCNQ1, Priori et al. (2005) identified a heterozygous missense mutation in the KCNJ2 gene (600681.0010). The mutation was not present in the unaffected mother or in the paternal grandparents, indicating that it may have occurred de novo in the father.
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 (2005) reviewed the clinical, electrophysiologic, and molecular features of 15 reported cases and 2 unpublished cases of short QT syndrome types 1, 2 (609621), and 3.