Stem Cells International / 2012 / Article / Tab 1

Review Article

Prospective In Vitro Models of Channelopathies and Cardiomyopathies

Table 1

HRS/EHRA Expert Consensus Statement on Genetic Testing (Heart Rhythm 2011; 8 : 1308–1339).

Cardiac Channelopathy
/Cardiomyopathy
Diagnostic implications of genetic testingClass IClass IIaClass IIbClass IIITesting genesCommon disease genes
“is recommended”“can be useful”“may be considered”“is not recommended”Genes% of disease

Long QT syndrome
(LQTS)
Patient in whom a cardiologist has established a strong clinical index of suspicion for LQTSComprehensive or LQT1-3
Asymptomatic patient with QT prolongation in the absence of other clinical conditions that might prolong the QT interval on serial 12-lead ECGs defined as QTc >480 ms (prepuberty) or >500 ms (adults)KCNQ1 (LQT1)
KCNH2 (LQT2)
SCN5A (LQT3)
LQT4-13
30–35%
25–40%
5–10%
>5%
Asymptomatic patient with otherwise idiopathic QTc values >460 ms (prepuberty) or >480 ms (adults) on serial 12-lead ECGs Mutation-specific
Family members and other appropriate relatives subsequently following the identification of the LQTS-causative mutation in an index case

Catecholaminergic polymorphic ventricular tachycardia (CPVT)Patient in whom a cardiologist has established a clinical index of suspicion for CPVTComprehensive or CPVT1 and CPVT2RYR2 (CPVT1)60%
Family members and appropriate relatives following identification of the CPVT-causative mutation in an index caseMutation-specificCASQ2 (CPVT2)3–5%

Brugada syndrome (BrS)Family members and appropriate relatives following identification of the BrS-causative mutation in an index caseMutation-specificSCN5A (BrS1)20–30%
Patient in whom a cardiologist has established a clinical index of suspicion for BrSComprehensive or SCN5A
The setting of an isolated type2 or type3 Brugada ECG pattern

Progressive cardiac conduction disorders (CCD)Family members and appropriate relatives following the identification of the CCD-causative mutation in an index caseMutation-specificSCN5A5%
Patients with either isolated CCD or CCD with concomitant congenital heart disease, especially when there is documentation of a positive family history of CCDSCN5A and TRPM4

Short QT syndrome (SQTS)Family members and appropriate relatives following the identification of the SQTS-causative mutation in an index caseMutation-specific
KCNH2 (SQT1)
KCNQ1 (SQT2)
KCNJ2 (SQT3)
>5%
>5%
>5%
Patient in whom a cardiologist has established a strong clinical index of suspicion for SQTS based on examination of the patient's clinical history, family history, and electrocardiographic phenotypeComprehensive or SQT1-3

Atrial fibrillation (AF)Genetic testing is not indicated for atrial fibrillation at this time.None of the known
disease-associated
genes has been
shown to account
for >5% of this disease.

Hypertrophic cardiomyopathy (HCM)Patient in whom a cardiologist has established a clinical diagnosis of HCMComprehensive or targeted (MYBPC3, MYH7, TNNI3, TNNT2, and TPM1)MYBPC3
MYH7
TNNT2
TNNI3
TPM1
20–45%
15–20%
1–7%
1–7%
>5%
Family members and appropriate relatives following identification of the HCM-causative mutation in an index caseMutation-specific

Arrhythmogenic cardiomyopathy (ACM)/Arrhythmogenic right ventricular cardiomyopathy (ARVC)Family members and appropriate relatives following identification of the ACM/ARVC-causative mutation in an index caseMutation-specificPKP2
DSG2
DSP
DSC2
TMEM43
25–40%
5–10%
2–12%
2–7%
>5%
Patients satisfying task force diagnostic criteria for ACM/ARVCComprehensive or targeted (DSC2, DSG2, DSP, JUP, PKP2, and TMEM43)
Patients with possible ACM/ARVC (1 major or 2 minor criteria) according to the 2010 task force criteria (European Heart Journal)
Patients with only a single minor criterion according to the 2010 task force criteria

Dilated cardiomyopathy (DCM)Patients with DCM and significant cardiac conduction disease (i.e., first-, second-, or third-degree heart block) and/or a family history of premature unexpected sudden death
Family members and appropriate relatives following the identification of a DCM-causative mutation in the index caseComprehensive or targeted (LMNA and SCN5A)
LMNA
SCN5A
>5%
>5%
Patients with familial DCM to confirm the diagnosis, to recognize those who are at highest risk of arrhythmia and syndromic Mutation-specific
features, to facilitate cascade screening within the family, and to help with family planningMutation-specific

Left ventricular noncompaction (LVNC)Family members and appropriate relatives following the identification of an LVNC-causative mutation in the index caseMutation-specific
LBD3, and so forth
LBD3~5%
Patients in whom a cardiologist has established a clinical diagnosis of LVNC

Restrictive cardiomyopathy (RCM)Family members and appropriate relatives following the identification of an RCM—causative mutation in the index caseMutation-specificβ-MHC~5%
Patients in whom a cardiologist has established a clinical index of suspicion for RCMMYH7, TNNI3, TNNT2 TNNI3~5%

Out-of-hospital cardiac arrest survivorsThe survivor of an Unexplained Out-of-Hospital Cardiac ArrestAppropriate genes following diagnosis of the survivor
RYR2
KCNQ1
KCNH2
10–15%
5–10%
~5%
Routine genetic testing, in the absence of a clinical index of suspicion for a specific cardiomyopathy or channelopathy

Postmortem genetic
testing in sudden death cases (SUD/SIDS)
For all SUDS and SIDS cases, collection of a tissue sample
In the setting of autopsy negative SUDScomprehensive or targeted (RYR2, KCNQ1, KCNH2, and SCN5A)
Mutation-specific
RYR2
KCNQ1
KCNH2
SCN5A
SCN5A: 3–5%
Family members and other appropriate relatives following identification of a SUDS-causative mutation in the decedent

HRS: the Heart Rhythm Society, EHRA: European Heart Rhythm Association. We summarized their tables with permission.

We are committed to sharing findings related to COVID-19 as quickly as possible. We will be providing unlimited waivers of publication charges for accepted research articles as well as case reports and case series related to COVID-19. Review articles are excluded from this waiver policy. Sign up here as a reviewer to help fast-track new submissions.