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