Table 1.
Genetic basis of long-QT syndrome and multisystem syndromes associated with QT prolongation.
| Gene (Genotype) | Locus | Protein | Functional Effect | Mode of Inheritance | Frequency | Ref. |
|---|---|---|---|---|---|---|
| Long QT Syndrome (Major) | ||||||
| KCNQ1 (LQT1) | 11p15.5 | Kv7.1 | Reduced IKs | AD; AR | 30–35% | [16, 25] |
| KCNH2 (LQT2) | 7q35-46 | Kv11.1 | Reduced IKr | AD | 25–30% | [17] |
| SCN5A (LQT3) | 3p21-p24 | Nav1.5 | Increased INa | AD | 5–10% | [18] |
| Long QT Syndrome (Minor) | ||||||
| AKAP9 (AKAP9-LQTS) | 7q21-q22 | Yotiao | Reduced IKs | AD | <1% | [38] |
| CACNA1C (CACNA1C-LQTS) | 12p13.3 | Cav1.2 | Increased ICa,L | AD | <1% | [132] |
| CAV3 (CAV3-LQTS) | 3p25 | Caveolin 3 | Increased INa | AD | <1% | [45] |
| KCNE1 (KCNE1-LQTS) | 21q22.1 | MinK | Reduced IKs | AD | <1% | [37] |
| KCNE2 (KCNE2-LQTS) | 21q22.1 | MiRP1 | Reduced IKr | AD | <1% | [40] |
| KCNJ5 (KCNJ5-LQTS) | 11q24 | Kir3.4 | Reduced IK,ACh | AD | <1% | [48] |
| SCN4B (SCN4B-LQTS) | 11q23. 3 | Nav1.5 β4-subunit | Increased INa | AD | <1% | [46] |
| SNTA1 (SNTA-LQTS) | 20q11.2 | Syntrophin-α1 | Increased INa | AD | <1% | [47] |
| Jervell and Lange-Nielson Syndrome | ||||||
| KCNQ1 (JLNS1) | 11p15.5 | Kv7.1 | Reduced IKs | AR | Very rare | [24] |
| KCNE1 (JLNS2) | 21q22.1 | MinK | Reduced IKs | AR | Very rare | [39] |
| Ankyrin-B Syndrome | ||||||
| ANKB (ABS) | 4q25-q27 | Ankyrin B | Aberrant ion channel/transporter localization | AD | <1% | [51] |
| Andersen-Tawil Syndrome | ||||||
| KCNJ2 (ATS) | 17q23 | Kir2.1 | Reduced IK1 | AD | <1% | [56] |
| Timothy Syndrome | ||||||
| CACNA1C (TS) | 12p13.3 | Cav1.2 | Increased ICa,L | Sporadic | Very rare | [8] |
| Recurrent Infantile Cardiac Arrest Syndrome | ||||||
| CALM1 | 14q24-q31 | Calmodulin 1 | Dysfunctional Ca2+ signaling | Sporadic | <1% | [63] |
| CALM2 | 2p21 | Calmodulin 2 | Dysfunctional Ca2+ signaling | Sporadic | <1% | [63] |
Abbreviations: AD, autosomal dominant; AR, autosomal recessive; ABS, Ankyrin-B syndrome; ATS, Andersen Tawil syndrome; LQTS, long-QT syndrome; and TS, Timothy syndrome.