Long QT syndrome 1

General Information (adopted from Orphanet):

Synonyms, Signs: LQT1/2, DIGENIC, INCLUDED
VENTRICULAR FIBRILLATION WITH PROLONGED QT INTERVAL LONG QT SYNDROME 1/2, DIGENIC, INCLUDED
LONG QT SYNDROME 1, ACQUIRED, SUSCEPTIBILITY TO, INCLUDED
WARD-ROMANO SYNDROME
ROMANO-WARD SYNDROME
LQT1
WRS
RWS
LQT1
Number of Symptoms 14
OrphanetNr:
OMIM Id: 192500
ICD-10:
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal dominant
20301308 [IBIS]
Age of onset:

Disease classification (adopted from Orphanet):

Parent Diseases: Romano-Ward syndrome
 -Rare cardiac disease
 -Rare genetic disease

Comment:

LQT1 is a sub-type of Romano-Ward syndrome, a variant of the familial long QT syndrome. It is characterized by mutations in the KCNQ1 gene. A specific trigger for arrhythmic events in LQT1 subtype is physical exertion, especially swimming, or emotional stress. Typically, ECG shows a broad T wave. (PMID:25274057; 26370830)

Symptom Information: Sort by abundance 

1
(HPO:0005135) EKG: T-wave abnormalities Very frequent [IBIS] 20301308 IBIS 19 / 7739
2
(HPO:0012266) T-wave alternans Frequent [IBIS] 25274057; 25800484 IBIS 8 / 7739
3
(HPO:0001657) Prolonged QT interval Very frequent [IBIS] 25274057 IBIS 33 / 7739
4
(HPO:0005184) Prolonged QTc interval 25800484 IBIS 5 / 7739
5
(HPO:0001692) Primary atrial arrhythmia Frequent [IBIS] 33% (n=21) 19017345 IBIS 16 / 7739
6
(HPO:0004756) Ventricular tachycardia 25274057 IBIS 55 / 7739
7
(HPO:0004308) Ventricular arrhythmia 1884444 IBIS 46 / 7739
8
(HPO:0001664) Torsade de pointes Frequent [IBIS] 25274057; 20301308 IBIS 15 / 7739
9
(HPO:0001663) Ventricular fibrillation Frequent [IBIS] 25274057 IBIS 35 / 7739
10
(HPO:0001695) Cardiac arrest 25274057 IBIS 87 / 7739
11
(HPO:0001645) Sudden cardiac death 25274057 IBIS 84 / 7739
12
(HPO:0001279) Syncope Very frequent [IBIS] 25274057; 20301308 IBIS 94 / 7739
13
(HPO:0001250) Seizures 25274057 IBIS 1245 / 7739
14
(HPO:0011097) Epileptic spasms 25274057 IBIS 45 / 7739

Associated genes:

KCNQ1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
CALM2 rs398124647 likely pathogenic RCV000143836.1
CALM2 rs398124647 likely pathogenic RCV000143837.1
CALM2 rs398124648 likely pathogenic RCV000143838.1
CALM2 rs398124649 likely pathogenic RCV000143840.1
CALM2 rs398124650 likely pathogenic RCV000143839.1
KCNQ1 rs104894252 pathogenic RCV000003261.2
KCNQ1 rs120074177 pathogenic RCV000003260.2
KCNQ1 rs120074178 pathogenic RCV000003264.2
KCNQ1 rs120074179 pathogenic RCV000003265.2
KCNQ1 rs120074180 pathogenic RCV000003266.2
KCNQ1 rs120074181 pathogenic RCV000003262.2
KCNQ1 rs120074182 pathogenic RCV000003263.2
KCNQ1 rs120074183 pathogenic RCV000003270.2
KCNQ1 rs120074184 pathogenic RCV000003271.2
KCNQ1 rs120074185 pathogenic RCV000003274.2
KCNQ1 rs120074187 pathogenic RCV000003276.2
KCNQ1 rs120074190 pathogenic RCV000003288.2
KCNQ1 rs120074191 pathogenic RCV000003290.3
KCNQ1 rs120074193 pathogenic RCV000003294.2
KCNQ1 rs120074194 pathogenic RCV000003295.2
KCNQ1 rs12720459 pathogenic RCV000003269.2
KCNQ1 rs12720459 pathogenic RCV000003267.2
KCNQ1 rs151344631 pathogenic RCV000030815.2
KCNQ1 rs17221854 pathogenic RCV000003291.2
KCNQ1 rs1800171 pathogenic RCV000003283.2
KCNQ1 rs199472709 pathogenic RCV000115008.2
KCNQ1 rs199472776 likely pathogenic RCV000203070.1
KCNQ1 rs199473480 pathogenic RCV000174453.1
KCNQ1 rs267607197 pathogenic RCV000003296.2
KCNQ1 rs387906290 pathogenic RCV000003282.2
KCNQ1 rs397508105 pathogenic RCV000003284.3
KCNQ1 rs397508115 pathogenic RCV000003297.2
KCNQ1 rs587776555 pathogenic RCV000003278.2
KCNQ1 rs794728583 pathogenic RCV000193564.1

Additional Information:

Description: (OMIM) Congenital long QT syndrome is electrocardiographically characterized by a prolonged QT interval and polymorphic ventricular arrhythmias (torsade de pointes). These cardiac arrhythmias may result in recurrent syncopes, seizure, or sudden death (Jongbloed et al., 1999).

A ...

Clinical Description OMIM Ward (1964) observed syncope due to ventricular fibrillation in a brother and sister whose resting electrocardiogram showed abnormal prolongation of the QT interval. The mother, although asymptomatic, had a prolonged QT interval also. Her sister had attacks of ...
Genotype-Phenotype Correlations OMIM In a large collaborative study, Zareba et al. (1998) demonstrated that the genotype of the long QT syndrome influences the clinical course. The risk of cardiac events (syncope, aborted cardiac arrest, or sudden death) was significantly higher among ...
Molecular genetics OMIM In affected members of 16 families with long QT syndrome, Wang et al. (1996) identified several mutations in the KVLQT1 gene (e.g., 607542.0001).

Russell et al. (1996) used SSCP analysis to screen 2 large and 9 ...

Diagnosis GeneReviews The diagnosis of Romano-Ward syndrome (RWS) is made on the basis of ECG characteristics, clinical presentation, and family history. Schwartz et al [1993] proposed a score system to diagnose RWS, which has recently been updated [Schwartz & Crotti 2011]. Points are assigned to various criteria (see Table 1). ...
Clinical Description GeneReviews Romano-Ward syndrome (RWS) is characterized by QT prolongation and T-wave abnormalities on ECG that are associated with tachyarrhythmias, typically the ventricular tachycardia torsade de pointes (TdP). TdP is usually self-terminating, thus causing syncope, the most common symptom in individuals with RWS. Syncope is typically precipitous and without warning. In some instances, TdP degenerates to ventricular fibrillation and aborted cardiac arrest (if the individual is defibrillated) or sudden death....
Genotype-Phenotype Correlations GeneReviews The known genotype-phenotype correlations are described in Table 4....
Differential Diagnosis GeneReviews LQTS with syndactyly (Timothy syndrome or syndactyly-related LQTS) is characterized by cardiac (LQTS and/or congenital heart defects), hand (variable unilateral or bilateral cutaneous syndactyly of fingers or toes), facial, and neurodevelopmental features. LQTS typically manifests with a rate-corrected QT interval between 480 ms and 700 ms. Facial anomalies include: flat nasal bridge, low-set ears, thin upper lip, and round face. Neurologic symptoms include: autism, seizures, intellectual disability, and hypotonia. Ventricular tachyarrhythmia is the leading cause of death; average age of death is 2.5 years. Timothy syndrome is diagnosed by clinical features and by the presence of the de novo p.Gly406Arg mutation in the CaV1.2 calcium channel gene, CACNA1C, the only gene known to be associated with Timothy syndrome [Splawski et al 2004]....
Management GeneReviews To establish the diagnosis in an individual suspected of having Romano-Ward syndrome (RWS), determine whether symptoms are attributable to LQTS or to some other disorder. For example, dizziness, pre-syncope, palpitations, vasovagal syncope, and orthostatic syncope are common in the general population and rarely caused by LQTS. Treatment decisions should be based on LQTS-related events, not on unrelated disorders....
Molecular genetics GeneReviews Information in the Molecular Genetics and OMIM tables may differ from that elsewhere in the GeneReview: tables may contain more recent information. —ED....