TABLE 1.
Summarization of reported PRKAG2 variants patients
| Reference | Variant site | Onset age/gender | Primary symptom | Cardiac manifestations | ECG | Echo | Clinical outcome |
|---|---|---|---|---|---|---|---|
| Austin et al. (2017) | p.G100S | 2.5 m/M | Generalized muscle weakness | HCM | sPR | Mild hypertrophy of the IVS | Alive |
| Zhang et al. (2013) | p.G100S (n = 13) | 16–38y/7 M&6F | Symptomatic arrhythmia | HCM |
Bradycardia CRBBB WPW II° or III°AVB |
Thickness of IVS |
4 died (30.7%) 4 PM 2 died after PM 1 died after treatment |
| van der Steld et al. (2017) | p.K290I | 27y/M | Syncope since infancy |
Arrhythmia LVH |
Sinus bradycardia RBBB |
LVH |
Alive Pacemaker |
| Banankhah et al. (2018) | p.R302Q | 23y/F | Persistent angina | HCM |
WPW RBBB |
LVH (22 mm) LVEF, 70%–75% |
Alive |
| Back Sternick et al. (2016) | p.R302Q | 52y/M | III°AVB |
Arrhythmia HCM |
III°AVB | LVH | Unknown |
| Roberts et al. (2010) | p.R302Q | 23y/M | Syncope |
HCM WPW |
sPR | LV hypertrophy and outflow obstruction | Cardiac transplantation |
| Charron et al. (2007) | p.R302Q | 22–66y/4F |
Dizzy Cardiopalmus |
Arrhythmia HCM |
sPR, RBBB, | Atrial hypertrophy | Alive |
| Spentzou et al. (2020) | p.Af304G | 13y/M | Ventricular fibrillation Cardiac arrest |
Arrhythmia LVH |
WPW SVT AVB AF |
LVH | Unknown |
| Yang et al. (2017) | p.V336L | 17–32y/1 M&1F |
Dizziness ECG anomaly |
HCM |
WPW V5‐V6 inverted T waves |
IVS (12 mm) LVH RVH EF, 46% |
1 Alive and 1 died |
| Laforêt et al. (2006) | p.S356P | 38y/M | Syncope |
Arrhythmia HCM |
SR (35/min) III°AVB LBBB |
IVST 18 mm LVEF = 60% |
Alive |
| Akman et al. (2007) | p.R384T | 10w/F | Fetal bradycardia |
Bradycardia HCM |
sPR |
IVST 15.2 mm LVEF = 81% |
Died |
| Liu et al. (2013) | p.K485E (n = 19) | 15–46y/15 M&4F |
Chest pain Palpitation Syncope |
HCM Arrhythmia |
Abnormal repolarization RBBB Bradycardia LVH WPW AVB |
LVH Thickness of IVS |
Unknown |
| Kelly et al. (2009) | p.E506D | 6 m/M |
WPW HCM |
HCM | sPR | Obliteration of the left ventricular cavity during systole | Cardiac transplantation |
| Gorla et al. (2018) | p.R531Q | 28wk of gestation/− | Echo\ECG anomaly | HCM | sPR | Severe biventricular hypertrophy and asymmetric septal hypertrophy | Died at 1 m |
| Burwinkel et al. (2005) | p.R531Q | 28 wk of gestation/− |
Bradycardia in fetus ARDS Multiserous cavity effusion |
Bradycardia HCM |
sPR (0.06 s) Enlarged QRS complexes Depressed ST segments |
Atrial hypertrophy Biventricular hypertrophy |
Died |
| Gollob, Seger et al. (2001) | p.R531G | 2y/M | Syncope |
Arrhythmia LVH |
AF WPW AVB |
LVH (11 mm) | Unknown |
| Murphy et al. (2005) | P.N488I (n = 40) | 3–45y (19)/− |
Asymptomatic (35%) Syncope (12.5%) Myalgia (18%) Stroke (3%) SCD (2.5%) |
arrhythmia may HCM |
WPW (58%) AF/SVT (30%) |
LVH (70%) 13–45 mm |
PM (30%) |
|
p.R302Q (n = 5) |
15–38y (26)/− | Syncope (100%) |
arrhythmia may HCM |
WPW (100%) AF/SVT (75%) |
LVH 15–16 mm |
PM (100%) | |
| Arad et al. (2002) |
p.R302Q (n = 43) |
39 ± 16y/− |
Arrhythmia SCD (n = 2) |
Arrhythmia LVH |
WPW (65%) SR (12%) AVB (37%) |
LVH (17.1 ± 7.6 mm) | PM (47%) |
| p.T400N | 42/− |
WPW Bradycardia |
Arrhythmia LVH |
WPW SR |
LVH (22 mm) | PM | |
|
p.N488I (n = 26) |
32 ± 13y/− |
WPW (23%) Bradycardia (31%) SCD (n = 2) |
Arrhythmia LVH |
WPW SR |
LVH (19.3 ± 9.3 mm) | PM (15%) | |
| Sri et al. (2019) |
p.N488I (n = 4) |
5–33y/3 M&1F |
Decreased activity tolerance Chest pain Echo\ECG anomaly |
HCM |
WPW sPR IRBBB |
LVH Thickness of IVS |
Alive |
|
p.E506D (n = 3) |
8–44y/2 M&1F |
Dizzy Palpitation Dyspnea |
HCM |
WPW sPR IRBBB |
LVH Thickness of IVS |
Alive | |
| Hu et al. (2020) |
p.R302Q (n = 8) |
15–40y/6 M&2F |
Chest pain Palpitation Syncope |
Arrhythmia HCM |
III°AVB Premature beat CLBBB WPW Bradycardia |
Thickness of IVS | PM |
| p.L341S | 15y/M | Negative |
Arrhythmia HCM |
II°AVB |
Thickness of IVS EF 42% |
PM | |
|
p.H401D (n = 2) |
14–26y/1 M&1F |
Palpitation Syncope |
Arrhythmia HCM |
2:1 heart block Premature beat WPW AF |
Thickness of IVS EF 40% |
Unknown | |
| p.K485E | 15y/M | Chest pain, chest distress, palpitation |
Arrhythmia HCM |
II°AVB WPW Bradycardia Premature beat |
Thickness of IVS (32 mm) EF 42% |
PM |
Abbreviations: AF, atrial fibrillation; AH, atrial hypertrophy; AVB, atrioventricular block; BH, biventricular hypertrophy; CMR, cardiac magnetic resonance; Echo, echocardiography; EF, ejection fraction; HCM, hypertrophic cardiomyopathy; IVS, interventricular septum; IVST, interventricular septum thickness; LAHB, Left anterior branch block; LBBB, left bundle branch block; LV, left ventricular; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; LVPW, left ventricular posterior wall; LVWT, left ventricular wall thickness; MLVWT, maximal left ventricular wall thickness; PM, pacemaker implantation; RBBB, right bundle branch block; SCD, sudden cardiac death; sPR, short PR; SR, sinu rhythm; SVT, supraventricular tachycardia; WPW, Wolff–Parkinson–White syndrome.