CLINICAL DATA ON INDIVIDUAL PATIENTS IN THE SQTS LITERATURE 2000-2018
(49 publications with 219 patients from 144 families)
|Gene/Mut||Age & gender||Presentation||QT/QTc||HR|
P = Proband | Fx = Family history
|KCNH2/N588K||17 YO F(P)||AF at young age||280/300||69|
|Same||21 YO M||Fx of SQTS||272/267||57|
|Same||51 YO F||Fx of SQTS||260/289||75|
|Not Done||37 YO F(P)||SCD||266/248||52|
|KCNH2/N588K||35 YO M(P)||Sync/Fx SCD||240/280||82|
|Same||31 YO F||Fx SCD||240/290||88|
|Same||6 YO M||Ab SCD||260/270||65|
|KCNH2/N588K||62 YO F(P)||SCD||210/250||85|
|Same||67 YO F||Fx SCD||270/295||72|
|Same||15 YO M||Sync/Fx SCD||260/300||80|
|Same||40 YO F||Fx SCD||240/268||75|
|negative||51 YO M (P)||Ab SCD||280/288||81|
|negative||20 YO M||Fx SCD||290/293||61|
|KCNQ1/V307L||70 YO M (P)||Ab SCD||290/302||65|
|Not Done||27 YO M (P)||Incidental finding||302/315||65|
|negative||15 YO M(P)||Ab SCD||300/335||67|
|Episodes of nocturnal seizure-like activity with SOB and fast heart rate.|
|(INCOMPLETE DATA (NO HR OR QT INTERVAL REGISTERED IN 2 PATIENTS)|
|KCNJ2/D172N||5 YO F(P)||Incidental finding||?/315|
|KCNJ2/D172N||35 YO M||Fx of SQTS||?/320|
|not done||20 YO M(P)||AF at young age||308/257||42|
|KCNQ1-V141M||Newborn F(P)||AF at young age||280/AF|
Eur Heart J
|MULTICENTER study of 29 patients, but only 10 new families and 22 new patients|
|neg||49 YO M(P)||Fx of SCD||275/303||73|
|39 YO M||Fx of SCD/sync||290/311||69|
|50 YO M||Fx of SCD/sync||280/313||75|
|21 YO M||Fx of SCD||300/310||64|
|neg||18 YO M(P)||Ab SCD||270/308||78|
|80 YO M||Fx of SCD||280/302||70|
|53 YO M||Fx of SCD||300/315||66|
|neg||35 YO F (P)||Fx of SCD||320/317||59|
|14 YO M||Fx of SCD, sync.||240/282||83|
|16 YO F||Fx of SCD||300/333||74|
|neg||17 YO M (P) Ab SCD||210/291||114|
|43 YO M||Fx of SCD||290/338||82|
|neg||16 YO M(P)||Ab SCD||280/317||77|
|19 YO M||Fx of SCD||294/324||73|
|21 YO M||Fx of SCD||320/333|
|not done||30 YO M(P)||SCD during sleep||315/302|
|52 YO F||Fx of SCD||310/327|
|25 YO M||Fx of SCD||315/323|
|neg||19 YO M(P)||Ab SCD/Fx SCD||300/317|
|neg||4 MONTH F(P)||Ab SCD/Fx SCD||210/307|
|neg||69 YO M(P)||Sync/Fx SCD||240/294|
|not done||28 YO M(P)||SCD||300/312|
|not done||30 YO F(P)||Ab SCD||270/292|
|7 YO F||Fx of SCD||290/308|
|53 YO F||Fx of SCD||290/300|
|6 new patients with INCOMPLETE DATA (IN 6 no HR AND QT and IN 5 no age)|
|CACNB2b-S481L||25 YO M(P)||Ab SCD||?/320||-|
|Same||? YO F||Fx SCD||?/370||-|
|Same||? YO F||Fx SCD||?/368||-|
|Same||? YO F||Fx SCD||?/340||-|
|Same||23 YO M||Fx SCD||?/340||-|
|Same||? YO M||Fx SCD||?/345||-|
|SQTS defined as QTc </= 360 ms in males and </= 370 ms in females.|
|CACNA1C-G490R||41 YO M(P)||Fx SCD||300/346||80|
|INCOMPLETE DATA (QT AND HR MISSING IN 1 PATIENT):|
|CACNA1C-A39V||44 YO M(P)||Fx SCD||?/360||-|
|Neg.||24 YO M(P)||Fx of SCD||313/308||58|
|KCNH2-T618I||23 YO M(P)||Fx of SCD||250/264||67|
|INCOMPLETE DATA (QT AND HR MISSING IN 1 PATIENT|
|Same||42 YO F||Fx of SCD||?/320|
|Not Done||21 YO F(P)||Ab SCD||280/215||35|
Can J Cardiol
|KCNH2-E50D||22 YO M(P)||Syncope||364/381||66|
|INTERNATIONAL MULTICENTER CASE SERIES INVOLVING 8 CENTERS with 10 pediatric patients, 7-19 years old (four 16-19), all male, only presented in the discussion section of the article entitled:
"Short QT Syndrome in a Pediatric Patient": Most (9?) patients published previously.
|Not Done||13 YO M(P)||Ab SCD||300/310||64|
Int J Cardiol
|KCNH2-R1135H||34 YO M(P)||SQT/Routine ECG||315/329||65|
|Chinese publication in Chinese of a family with hx of 4 members with SCD. Four other members were diagnosed with Short QT and QTc less than 320 msec. One received an ICD. [Chinese publication in Chinese of a family with hx of 4 members with SCD. Four other members were diagnosed with Short QT and QTc less than 320 msec. One received an ICD. http://www.ncbi.nlm.nih.gov/pubmed/19781151|
Clin Res Cardiol
|INCOMPLETE DATA: 1 new patient with unknown gender:|
|Negative||17 YO ?(P)||Recurrent syncope||320/283||47|
|MULTICENTER STUDY with INCOMPLETE DATA.
(12 patients with SQTS either referred to their institution or from previous reports) SQTS defined as QTc </= 330 ms or QTc </ = 360 ms when positive SQTS mutation is present.
|KCNH2-T618I||45 YO M(P||Ab SCD||276/298||69|
|NEW PATIENTS WITH INCOMPLETE DATA (No age):|
|Same||? YO F||Fx SQTS/CA||320/346||70|
|Same||? YO F||Fx SQTS/CA||308/308||60|
|Same||? YO F||Fx SQTS/CA||295/315||68|
|Giustetto C. JACC 2011||MULTICENTER STUDY - THE EUROPEAN SQTS REGISTRY|
|20 new patients with INCOMPLETE DATA and NOT CHARACTERIZED INDIVIDUALLY: 33 of the 53 patients in this paper have all been published previously: They are most likely the 29 patients from 11Giu06 and the last 4 patients from 22Sun11 even though this later study is not a European and not among the list of authors/hospitals mentioned?. The 20 NEW patients are not characterized individually, but CONSISTS OF 18 MALES AND 2 FEMALES. 53 patients (75% males) from 29 proband-identified families. Median age (males and females): 26 years (interquartile range: 17-39 years)|
|Cardiac arrest was similar in males and females (35% vs. 30%; p = o.15) In males more than 90% of CA events occurred between 14 and 40 years of age, whereas in females the events were spread across the entire lifespan, but included very few events. The distribution in males corresponds to the age with the highest testosterone plasma (saliva?) levels (Ref 20). These hormonal influences have been considered protective in post-puberal boys and men in the context of the long QT syndrome (Ref 22). The role of testosterone in SQTS has not been studied. Syncope was observed only in males. Most events occurred in males. FU data on mixed treatments ICD/antiarrhythmics. Very few events (Fig 5). Patients with a HERG mutation constituted a subgroup with specific characteristics such as a greater proportion of affected females and a higher prevalence of AF compared to non-HERG patients. Morover, HERG patients exhibited shorter QT intervals and ERPs then non-HERG.|
|Genetic: 5 mutations in 22 out of 30 index patients who were gene-analysed. SQTS defined as QTc < /= 340msec and < /= 360 ms associated with SCD, aborted SCD or syncope of arrhythmic origin.|
|Templin C. Eur Heart J 2011||CACNA2D1-S755T||17 YO F(P)||Ab SCD||317/329||65|
|Chinushi M. J. Cardiovasc. Electrophysiol 2012||KCNH2-N588K||38 YO F(P)||Syncope||260/300||80|
|same||11 YO M||Fx of SQTS||272/311||79|
|Hattori T. Cardiovasc. Res. 2012||KCNJ2-M301K||8 YO F(P)||Incidental finding||172/194||76|
|Mental retardation, abnormal proliferation of oesophageal blod vessels, Epilepsy, Kawasaki disease and AF. VF induced by placing Swan-Ganz catheter in|
| BUN S.-S.
J. Cardiovasc. Electrophysiol. 2012
|negative||26 YO M(P)||Ab SCD||320/320||60|
|Mother was found to have short QT, but no further data reported about her.|
| Hong K.
Eur. J. Human Genetics 2012
|SCN5A-R689H||40YO M(P)||Fx SCD||320/348||71|
|In addition to SQT the ECG showed Brugada-like changes.|
| Babaoglu K.
Anadolu Kardiyol Derg 2012
|Not done||13 YO M (P)||Incidental finding||280/300||69|
| Villafane J.
|MULTICENTER REVIEW ARTICLE - International case series involving 15 centers INCOMPLETE DATA , NO INDIVIDUAL DATA:
25 pts. (21 M, 4 F) 21 yo or younger from 21 families with 5.9 years follow-up. Most patients published previously
"Our cohort was predominantly male (84%), reflecting a sex-specific prevalence 20% of cases were identified to have disease-causing mutations." Mutation was detected in 24 of index patients who underwent genetic testing.
| Deo M.
|KCNJ2-E299V||11 YO M(P)||AF at young age||200/200||60|
| Maltret A
Int. J. Cardiol 2013
|KCNQ1-V141M||Newborn F(P)||SB at birth||260/279||69|
|Newborn with inner ear abnormality.|
| Villafane J.
|KCNQ1-V141M||9 YO F(P)||AF at young age||260/317||90|
|not done||3 WK O M(P)||AF at young age||290/270||52|
|not done||9 YO M(P)||AF at young age||280|
|not done||3 YO F(P)||AF at young age||290/?|
|One patient published earlier is excluded)|
|Sadeghian S.Europace 2014||not done||26 yo M(P)||VT/palpitations||280/300||69|
Rev. Port. Cardiol. 2014
|negative||52 YO M(P)||Ab SCD||270/327||88|
|Ambrosini E.Human Mol Gen. 2014||KCNJ2-K346T||9 YO M(P)(Twin 1)||Autism-epilepsy||275/331||87|
|INCOMPLETE DATA (QT/QTc AND HR MISSING IN 1 PATIENT)|
|same||9 YO M (Twin 2)||Autism-epilepsy||? /?|
Pediatr. Int. 2014
|KCNH2-N588K||10 YO M(P)||Incidental finding||260/283||71|
|Health screening at school including ECG showing very short QT
INCOMLETE DATA (AGE IS MISSING IN 1 PATIENT)
|same||? YO F||Fx SQTS||260/283||71|
|Mazzanti A. JACC 2014||
INHERITED ARRHYTHMIAS DATABASE, PAVIA, ITALY (Silvia G. Priori)
None of these patients have been previously published.
(Page 1301, line 6: “Here we present for the first time data pertaining to 73 SQTS patients identified in 47 families”from Italy, Poland and USA
INCOMPLETE DATA IN FORM OF MISSING INFORMATION ABOUT THE INDIVIDUAL PATIENTS
73 new patients (61 male, 12 female) from 47 proband-identified families. When the diagnosis is established based upon clinical parameters excluding the contribution of genetic testing the predominance of male patients is overwhelming (91%), suggesting that SQTS has, like BrS, a sex-dependent penetrance.
None of the genes related to SQTS identified a disease causing mutation in > 5% of clinically affected probands. All mutations found in this study showed a complete penetrance in carriers. A pathogenic mutation in K-channels was identified in 5 of 45 (11%): 2 in KCNJ2 gene (D172N, E299V), 2 in KCNH2 (N588K, T618I) and 1 in KCNQ1 (R259H). One in a CACNA1C gene(R1977Q).
A significant shorter QTc interval was found in mutation carriers versus noncarriers.
In familial cases, half of the first-degree relatives screened were clinically affected, consistent with a autosomal dominant pattern of inheritance.
Median age: 26 years +/- 15 (NO SEPERATION IN MALES AND FEMALES)
Life threatening arrhythmias were similar in males and females (30% vs 15 %, p=0.49).
There data identified a peak incidence of CA in the first year of life (4% per year). A quiescent phase encompassing adolescence, followed by an annual CA event rate of 1.3% between 20 and 40 years of age. “We should not consider affected female patients at lower risk of CA” (?)
Neither the presence of a very short QT interval nor the history of syncope alone identifies patients at higher risk of CA. The only predictor of malignant arrhythmias at follow-up is having experienced a first CA.
The majority (83%) of CAs occurred under resting condition or during sleep.
19 presented with SCD, 9 with syncope, 2 with Fx SCD and 17 SQTS as an incidental finding.
SQTS defined as QTc </= 340 msec or </= 360 msec combined with history of CA or syncope, a family history of unexplained CA at age </= 40 of age or a family history of SQTS
| Harrell D.T.
Int. C. Cardiol. 2015
|KCNH2-I560T||64 YO M(P)||Incidental finding||287/319||71|
|KCNH2-T618I||39 YO F(P)||Ab SCD||357/322||48|
|INCOMPLETE DATA IN 2 PATIENTS):|
|same||42 YO M||Fx of Ab SCD||?/330|
|same||14 YO M||Fx of Ab SCD||?/330|
|KCNQ1-V141M||10 YO F(P)||Fetal brady/SB at birth||270/280||65|
|INCOMPLETE DATA IN 1 PATIENT):|
|same||3 YO M||AF/brady at 3 years of age||?/?|
|negative||17 YO F(P)||Ab SCD||280/330||83|
|KCNQ1-F279I||23 YO M(P)||Fx of SCD||330/356||70|
| Ergul Y.
Anat. J. Cardiol. 2015
|not done||14 YU M(P)||Fx SCD/syncope||310/320||64|
| Righi D.
Cardiology in the Young 2016
|KCNQ1-V141M||1 YO M(P)||Bradycardia in infancy||300/286||55|
| Sarquella-Brugada G.
Heart Rhythm 2016
|KCNQ1-V141M||0 YO F(P)||Brady/AF in infancy||230/270||82|
|INCOMPLETE DATA (QT AND HR MISSING IN 1 PATIENT):|
|KCNQ1-V141M||0 YO M(P)||Brady/AF in infancy||?/290|
|KCNQ1-V141M||0 YO F(P)||Fetal brady/AF in infancy||250/290||81|
| Giustetto C.
Heart Rhythm 2015
|KCNH2-T618I||16 YO M(P)||Fx of SCD||260/300||80|
|same||21 YO F||Fx OF SCD||280/340||88|
|same||47 YO F||Ab SCD||300/344||79|
|not done||34 YO F||SCD||270/300||74|
| Rothenberg I.
Heart Rhythm 2016
|KCNQ1-A287T||16 YO F(P)||Ab SCD||380/333||46|
| Hu D.
|KCNH2-T618I||30 YO M(P)||Fx of SCD||260/260||60|
|KCNH2-T618I||9 YO F(P)||Fx of SCD||270/300||74|
|(INCOMPLETE DATA (QT, HR AND GENDER MISSING IN 2 PATIENTS)|
|same||? YO M||Fam hx of SCD||? /328|
|same||? YO M||Fam hx of SCD||?/299|
|KCNH2-T618I||46 YO F(P)||FX of SCD||260/315||88|
|(INCOMPLETE DATA (QT, HR AND GENDER MISSING IN 1 PATIENT):|
|same||? YO M||Fam hx of SCD||?/320|
| Thorsen K.
Nature Com. 2017
|This is the first report in two unrelated families of a mutation in the SLCAA3 gene which encodes the cardiac chloride-bicarbonate exchanger AE3 being associated with SQTS. The mutation causes reduced surface expression of AE3 and reduced bicarbonate transport. Sic4a3 knockdown in zebrafish causes increased cardiac pHi and short QT.|
|SLCAA3||39 YO M(P)||Abort SCD||320/320||60|
|same||74 YO F||Fx of SCD||320/348||70|
|same||66 yo F||Fx of SCD||300/355||85|
|same||64 yo M||Fx of SCD||360/332||51|
|same||63 yo F||Fx of SCD||300/300||60|
|same||56 YO F||Fx of SCD||280/346||92|
|same||55 YO F||Fx of SCD||320/335||82|
|same||50 YO M||Fx of SCD||360/360||60|
|same||43 YO M||Syncope/Fx of SCD||300/337||76|
|same||56 YO M||Fx of SCD||300/335||75|
|same||40 YO F||Fx of SCD||320/345||70|
|same||43 YO F||Fx of SCD||360/345||70|
|same||36 YO M||Syncope /Fx of SCD||320/320||60|
|same||39 YO M||Fx of SCD||320/320||60|
|same||37 YO F||Fx of SCD||280/323||80|
|same||32 YO F||Fx of SCD||300/333||72|
|same||34 YO M||Fx of SCD||300/320||68|
|same||26 YO F||Fx of SCD||300/355||85|
|same||32 YO M||Fx of SCD||340/370||65|
|same||30 YO M||DCM/Fx of SCD||320/367||79|
|same||16 YO M||Fx of SCD||340/362||68|
|same||20 YO M||Fx of SCD||320/367||92|
|(13 males, 10 females. Five with symptoms all male 30-43 years of age)|
|not done||22 YO M(P)||SCD/Fx of SQTS||not available|
|SL4A3||61 YO F||Fx of SCD||300/355||84|
|same||64 YO F||Fx of SCD||360/360||60|
|same||65 YO M||Fx of SCD||340/354||65|
|same||25 YO M||Fx of SCD||320/345||70|
| Wakatsuki D.
IJC Heart & Vasculature 2018
|KCNH2-W927G||22 YO M(P)||Ab SCD||360/340||53|
|This mutation has previously been described in patients with Brugada Syndrome and some of them had a QTc < 360 msec. Family not examined.|
| Akdis D.
|INCOMPLETE DATA (QT AND HR MISSING IN 3 PATIENTS)|
|KCNH2-c1891T>G||6 YO F(P)||Fx SCD/SYNC||?/323|
|same||54 YO M||Fx of SCD||?/324|
|same||12 YO F||Fx of SCD||?/340|
|The missense mutation in this family in the KCNH2-gene has not previously been associated with SQTS. Some family members had in addition a missense variant in SCN10A c.5605C>T (p.Ser631Ala) which was not considered to have any clinical significance.|
HOW TO DEFINE SQTS?
Based upon these data my suggested definition of SQTS 2021 is:
QTc </= 340 msec at heart rates between 50 and 70 beats/min, or
QTc </= 370 msec at heart rates between 50 and 70 beats/min, when associated with a pathogenic mutation, family history of SCD at age </= 40 years old, survival of VT/VF episode in the absence of heart disease, atrial fibrillation at very young age and syncopal episode that strongly suggests a cardiac arrhythmia.
SPECIAL FEATURES OF PATIENTS WITH SQTS PRESENTED SCHEMATICALLY
REASON FOR REFERRAL OF 117 PROBANDS (FAMILIES with SQTS):
|Males||Females||MAZ14||Total # Pts|
|Syncope in a family with a hx of SCD||3||1||0||4|
|AF/Severe bradycardia at young age||8||8||16|
|TOTAL (Including 47 from 38Maz14)||45(64%)||25(36%)||47||117|
Giustetto11 does not specify reason for referral of 20 new patients and therefore not include.
Percent distribution of 129 patients by sex and age at 10 year increments.
|0-10||6 (27%)||16 (73%)|
|21-30||20 (83%||4 (17%)|
|31-40||9 (45%)||11 (55%)|
|41-50||9 (69%)||4 (31%)|
|51-60||5 (50%)||5 (50%)|
|60+||7 (50%)||7 (50%)|
|TOTAL||75 (58%)||54 (42%)|
|11-50||57 (69%)||26 (31%|
|Total number of articles describing new patients with SQTS:||49|
|Articles with a single case report (Often no attempt to examine family members)||24|
|Articles with a single family||10|
|Total number of patients in articles about SQTS||320|
|Not indicated whether new or previously published||46|
|Remaining SQTS population||234|
|Patients presented in review articles without individual data||93|
|Remaining (118 single center pts, 23 pts from multicenter studies)||141|
|Individual patients without individual age (11) or gender data(1)||12|
|Remaining SQTS patients with complete information||129 (75 M, 54 F)|
|No. of pts with individual data from multicenter studies (Giu-06 (22), Vil-09 (1))||23|
|No. of pts with individual data from small single center studies often single patients||118|
|Total number of patients with individual data||141|
|No. of new patients without individual data (Mazzanti-14 (73) +Giustetto-11 (20))||93|
|Total number of probands with SQTS and reason for referral mentioned||117|
|Total number of probands with clinical data incl. Age, gender, QT, QTc and/or HR:||109|
|Number of probands with individual clinical data incl. Age, gender, QT, QTc and/or HR:||71|