Sub-type
|
Frequency
|
Locus
|
Gene
|
Ion Channel Defect/ Protein
|
Mutation Effect
|
ECG finding
|
Therapy
|
LQTS 1
|
30-35%
|
11p15.5
|
KVLQT1 (KCNQ1)
|
α-subunit of slowly activating delayed rectifier K+
channel
|
¯K+
Efflux
|
Broad based t-wave
Late-onset
t-wave |
1.Avoid stress, strenuous exercise and swimming
2. β-blocker
3. ICD if
symptomatic on medical therapy
4. Can consider
ICD if Qtc > 500msec (controversial) |
LQTS 2
|
25-30%
|
7q35-36
|
HERG
|
α-subunit of rapidly activating delayed rectifier K+
channel
|
¯K+
Efflux
|
Widely split t-wave
Low-amplitude
t-wave |
1.Avoid loud stimuli an stress
2. β-blocker
3. Potassium +
Spironolactone (limited data, unclear safety)
4. ICD if
symptomatic on medical therapy
5. Can consider
ICD if Qtc > 500msec (controversial) |
LQTS 3
|
5-10%
|
3p21-24
|
SCN5A
|
α-subunit of voltage gated Na+ channel
|
Prolonged Na+ influx
|
Late onset t-wave that is biphasic or peaked
|
1.Avoid loud stimuli an stress
2. β-blocker + ?mexilitene?
3. ICD if
symptomatic on medical therapy
4. Can consider ICD in
men
if Qtc > 500msec (controversial)
|
LQTS 4
|
1-2%
|
4q25-27
|
ANKB
|
Ankyrin B adaptor protein that anchors Na+ -K+
ATPase and Na+ /Ca2+
exchanger
|
Build-up of Na+ within cell and Ca2+
outside of cell
|
Variable Qt interval prolongation
|
Limited data, probably benefit from β-blocker and then
ICD if symptomatic on medical therapy
|
LQTS 5
|
1%
|
21q22.1-2
|
Mink (KCNE1)
|
β-subunit of slowly activating delayed rectifier K+
channel
|
¯K+
Efflux
|
Not defined
|
Limited data, probably benefit from β-blocker and then
ICD if symptomatic on medical therapy
|
LQTS 6
|
rare
|
21q22.1
|
MiRP1
|
β-subunit of rapidly activating delayed rectifier K+
channel
|
¯K+
Efflux
|
Not defined
|
Limited data, probably benefit from β-blocker and then
ICD if symptomatic on medical therapy
|
LQTS 7
|
rare
|
17q23
|
KCNJ2
|
Inward rectifying potassium channel
|
¯K+
Efflux
|
Modest prolongation of Qt interval
|
?Verapamil?
ICD is symptomatic |
LQTS 8
|
rare
|
12p13.3
|
CACNA1C
|
α-subunit of L-type calcium channel
|
Prolonged Ca2+
influx
|
Exaggerated Qt interval prolongation
|
?Verapamil?
ICD if symptomatic |
LQTS 9
|
rare
|
3p25
|
CAV3
|
Caveolin-3 protein
|
Prolonged Na+ influx
|
Not defined
|
No data, probably benefit from β-blocker and then ICD if
symptomatic on medical therapy
|
LQTS 10
|
Extremely rare, found in 1 family
|
11q23
|
SCN4 β
|
β-subunit of voltage gated Na+ channel
|
Prolonged Na+ influx
|
Not defined
|
No data, probably benefit from β-blocker and then ICD if
symptomatic on medical therapy
|