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As of June 2005, three
different genetic mutations have been identified in families with SQTS.
Brugada et al discovered two families with two different
missense mutations, revealing the same amino acid change (N588K) in the
S5-P loop region of the cardiac IKr channel HERG
(KCNH2). These mutations dramatically increased IKr,
leading to heterogeneous abbreviation of action potential duration and
refractoriness, reducing the affinity of the channel to IKr
blockers.
Bellocq C et al
examined a 70-year-old man presenting with idiopathic ventricular
fibrillation and a QT interval of 290 ms. Analysis of candidate genes
identified a g919c substitution in KCNQ1 encoding the K+
channel KvLQT1. It is of interest to note that mutations in the same
two genes have lead to a decrease in function and are responsible for
the LQT2 and LQT1 syndromes, respectively. This finding suggests that
SQTS is a genetically heterogeneous disease similar to other inherited
arrhythmogenic disorders.
The most recent genetic
focus described by Priori SG et al is a mutation in KCNJ2
isolated in a five year-old child (QTc=315ms) and her father (QTc=320ms).
The group also describes a unique ECG pattern consisting of asymmetrical
T waves with a rapid terminal phase. The defect creates a G514A
substitution in the KCNJ2 gene with a change from aspartic acid to
asparagine at position 172 (D172N) resulting in a larger outward current
of cardiac IK1. The KCNJ2 focus is also associated
with patients with Andersen’s Syndrome.
Still other individuals with
SQTS have none of the known genetic abnormalities. These remaining
patients are afflicted by other single gene abnormalities not yet
elucidated or a host of abnormalities that cannot be isolated to a
single focus.
last updated:
09/30/2007 |
