PMC5775440_01
A depiction of the potassium channel, KvLQT1, encoded by the gene KCNQ1, is shown with 6 transmembrane domains (S1-S6) seen spanning the cardiomyocyte membrane. The site of the pathogenic variant identified in the proband:KCNQ1 c.1552C>T; p.R518X:is depicted by the blue circle in the C-terminus.
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He was treated with mexiletine until genetic testing exposed a maternally inherited truncating Swedish founder mutation in the C-terminal of KCNQ1 (c.1552C>T; p.R518X) (Figure 1).
A multigenerational family pedigree with the proband denoted by an arrow. Males are represented by squares and females by circles. Blue quadrants represent the KCNQ1 R518X genotype, and red quadrants represent long QT syndrome. A&W= alive and well; d. = died; MI = myocardial infarct; yo = years old.
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The deceased relatives were not genotyped and no further details were available (Figure 2).
Corrected QT intervals measured in the patient during the recovery period from exercise under the following conditions: A: on 20 mg nadolol therapy, B: on no therapy, C: post left cardiac sympathectomy denervation. The normal range (2nd to 98th percentiles) derived from control subjects is shown in gray.
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An exercise test was performed on our patient, which demonstrated a peak heart rate of 173 beats per minute and a QTc measured within the normal limits during the recovery period from exercise (Figure 3A). Given his prior normal QT response to exercise, a repeat test was performed after 3 days without nadolol therapy, which unmasked an LQTS phenotype in the late recovery period from exercise, with a maximal QTc of 520 ms recorded at 6 minutes (Figure 3B). Once steady state was achieved, he was re-exercised, which again demonstrated that the QTc was within normal limits during the recovery period (Figure 3C).