Familial long QT syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: LQTS
Congenital long QT syndrome
Number of Symptoms 23
OrphanetNr: 768
OMIM Id: 192500
220400
600919
601005
603830
611818
611819
611820
612347
612955
613485
613688
613693
613695
ICD-10: I45.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: 50 of 100 000 - PMID: 19841298 [IBIS]
Inheritance: Autosomal recessive
Autosomal dominant
- PMID: 1884444 [IBIS]
Age of onset: Childhood
Adolescent
- PMID: 1884444 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Genetic cardiac rhythm disease
 -Rare cardiac disease
 -Rare genetic disease

Comment:

Familial long QT syndrome (LQTS) is an inherited arrhythmia syndrome characterized by a prolonged QT interval. LQTS is divided into subtypes depending on the mutated gene. The most frequent LQTS subtypes are type 1 (LQT1), type 2 (LQT2) and type 3 (LQT3). T wave morphology may help to differentiate between LQT1, 2 and3. A broad T wave is observed in LQT1, a biphasic T wave in LQT2 and a late-appearing T wave in LQT3. LQTS is often mistreated as epilepsy because of generalized seizures. Up to now, 15 different genes have been reported to be associated with LQTS, but KCNQ1, KCNH2 and SCN5A are the most common genes (PMID:25274057).

Symptom Information: Sort by abundance 

1
 (HPO:0005135) EKG: T-wave abnormalities Very frequent [IBIS] 20301308 IBIS 19 / 7739
2
 (HPO:0001655) Patent foramen ovale 25417227 IBIS 31 / 7739
3
 (HPO:0011025) Abnormality of cardiovascular system physiology Very frequent [IBIS] Frequent [Orphanet] 1884444 IBIS 41 / 7739
4
 (HPO:0012266) T-wave alternans Rare [IBIS] 5% (n=20) 25274057 IBIS 8 / 7739
5
 (HPO:0001657) Prolonged QT interval Very frequent [IBIS] 25274057 IBIS 33 / 7739
6
 (HPO:0011675) Arrhythmia Very frequent [IBIS] Frequent [Orphanet] 22263042 IBIS 226 / 7739
7
 (HPO:0001688) Sinus bradycardia 25417227 IBIS 18 / 7739
8
 (HPO:0001662) Bradycardia Occasional [IBIS] 30% (n=20) 26550086 IBIS 41 / 7739
9
 (HPO:0001692) Primary atrial arrhythmia Frequent [IBIS] 33% (n=21) 19017345 IBIS 16 / 7739
10
 (HPO:0004756) Ventricular tachycardia 20301308 IBIS 55 / 7739
11
 (HPO:0004308) Ventricular arrhythmia Frequent [IBIS] 47% (n=328) 1884444 IBIS 46 / 7739
12
 (HPO:0001664) Torsade de pointes Occasional [IBIS] 15% (n=20) 26550086 IBIS 15 / 7739
13
 (HPO:0001663) Ventricular fibrillation 20301308 IBIS 35 / 7739
14
 (HPO:0001678) Atrioventricular block typical [HPO] Occasional [IBIS] 12574983 IBIS 59 / 7739
15
 (HPO:0001695) Cardiac arrest Occasional [IBIS] 25274057 IBIS 87 / 7739
16
 (HPO:0001645) Sudden cardiac death Occasional [IBIS] 25274057 IBIS 84 / 7739
17
 (HPO:0001279) Syncope Occasional [IBIS] 27.1% (n=496) 26823142 IBIS 94 / 7739
18
 (HPO:0000718) Aggressive behavior 22263042 IBIS 109 / 7739
19
 (HPO:0002870) Obstructive sleep apnea 26118557 IBIS 16 / 7739
20
 (HPO:0001250) Seizures 25274057 IBIS 1245 / 7739
21
 (HPO:0011097) Epileptic spasms Occasional [IBIS] 25274057 IBIS 45 / 7739
22
 (HPO:0000407) Sensorineural hearing impairment Very frequent [Orphanet] Rare [IBIS] 7% (n=328) 1884444 IBIS 524 / 7739
23
 (HPO:0008527) Congenital sensorineural hearing impairment hallmark [HPO] Rare [IBIS] 7% (n=328) 1884444 IBIS 165 / 7739

Associated genes:

KCNQ1; KCNH2; SCN5A; ANK2; KCNE1; KCNE2; KCNJ2; CACNA1C; CAV3; SCN4B; AKAP9; SNTA1; KCNJ5; CALM1; CALM2;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference
AKAP9 rs121908566 pathogenic RCV000006241.3
AKAP9 rs730880043 likely pathogenic RCV000157100.1
AKAP9 rs796052199 likely pathogenic RCV000190222.1
AKAP9 rs796052200 likely pathogenic RCV000190223.1
ANK2 rs121912706 pathogenic RCV000019676.27
ANK2 rs72544141 pathogenic RCV000019672.27
ANK2 rs755287627 likely pathogenic RCV000190219.1
ANK2 rs786205420 likely pathogenic RCV000190218.1
ANK2 rs796052197 likely pathogenic RCV000190220.1
ANK2 rs796052198 likely pathogenic RCV000190221.1
CACNA1C rs79891110 pathogenic RCV000199739.1
CALM1 rs199744595 pathogenic RCV000162063.2
CALM1 rs730882252 pathogenic RCV000162062.2
CALM1 rs730882253 pathogenic RCV000162064.2
CALM2 rs398124647 likely pathogenic RCV000143837.1
CALM2 rs398124647 pathogenic RCV000162068.2
CALM2 rs398124647 likely pathogenic RCV000143836.1
CALM2 rs398124647 pathogenic RCV000162067.2
CALM2 rs398124648 pathogenic RCV000162069.2
CALM2 rs398124648 likely pathogenic RCV000143838.1
CALM2 rs398124649 likely pathogenic RCV000143840.1
CALM2 rs398124649 pathogenic RCV000162070.2
CALM2 rs398124650 likely pathogenic RCV000143839.1
CALM2 rs398124650 pathogenic RCV000162066.2
CALM2 rs730882254 pathogenic RCV000162065.2
CAV3 rs104893713 pathogenic RCV000008788.3
CAV3 rs104893715 pathogenic RCV000008792.3
CAV3 rs121909281 pathogenic RCV000008793.2
CAV3 rs121909282 pathogenic RCV000008794.2
CAV3 rs72546668 pathogenic RCV000008791.2
CAV3 rs72546668 pathogenic RCV000008790.2
CAV3 rs796052171 likely pathogenic RCV000190168.1
DSP rs121912997 likely pathogenic RCV000157195.1
KCNE1 rs1805128 pathogenic RCV000014423.25
KCNE1 rs199473362 pathogenic RCV000171560.1
KCNE1 rs74315446 pathogenic RCV000014421.25
KCNE2 rs16991654 pathogenic RCV000006428.2
KCNE2 rs199473648 likely pathogenic RCV000171565.1
KCNE2 rs74315447 pathogenic RCV000006425.2
KCNE2 rs74315448 pathogenic RCV000006426.2
KCNH2 rs121912504 pathogenic RCV000015501.21
KCNH2 rs121912505 pathogenic RCV000015502.25
KCNH2 rs121912506 pathogenic RCV000015505.25
KCNH2 rs121912507 pathogenic RCV000015508.25
KCNH2 rs121912508 pathogenic RCV000015509.26
KCNH2 rs121912509 pathogenic RCV000015512.25
KCNH2 rs121912510 pathogenic RCV000015513.21
KCNH2 rs121912511 pathogenic RCV000015515.25
KCNH2 rs121912512 pathogenic RCV000015516.25
KCNH2 rs121912513 pathogenic RCV000015522.25
KCNH2 rs121912513 pathogenic RCV000015523.25
KCNH2 rs121912514 pathogenic RCV000015524.25
KCNH2 rs121912515 pathogenic RCV000015525.25
KCNH2 rs121912516 pathogenic RCV000015528.25
KCNH2 rs189014161 pathogenic RCV000157266.1
KCNH2 rs199472884 pathogenic RCV000157261.1
KCNH2 rs199472884 likely pathogenic RCV000198797.1
KCNH2 rs199472885 pathogenic RCV000171561.1
KCNH2 rs199472942 pathogenic RCV000022644.25
KCNH2 rs199472942 likely pathogenic RCV000190215.1
KCNH2 rs199472944 pathogenic RCV000022643.25
KCNH2 rs199473428 pathogenic RCV000157264.1
KCNH2 rs28928904 pathogenic RCV000015504.25
KCNH2 rs28928905 pathogenic RCV000015511.26
KCNH2 rs587777907 pathogenic RCV000144957.2
KCNH2 rs730880116 pathogenic RCV000157258.1
KCNH2 rs730880374 likely pathogenic RCV000157260.1
KCNH2 rs77331749 pathogenic RCV000015527.25
KCNH2 rs77331749 pathogenic RCV000015526.25
KCNH2 rs786204101 pathogenic RCV000168023.1
KCNH2 rs796052195 likely pathogenic RCV000190214.1
KCNH2 rs796052196 likely pathogenic RCV000190216.1
KCNH2 rs9333649 pathogenic RCV000015510.22
KCNJ5 rs199830292 pathogenic RCV000009405.4
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 rs120074188 pathogenic RCV000003280.3
KCNQ1 rs120074190 pathogenic RCV000003288.2
KCNQ1 rs120074191 pathogenic RCV000003290.3
KCNQ1 rs120074193 pathogenic RCV000003294.2
KCNQ1 rs120074194 pathogenic RCV000003295.2
KCNQ1 rs120074196 pathogenic RCV000003300.2
KCNQ1 rs12720459 pathogenic RCV000003267.2
KCNQ1 rs12720459 pathogenic RCV000003268.2
KCNQ1 rs12720459 pathogenic RCV000003269.2
KCNQ1 rs12720459 pathogenic RCV000171124.1
KCNQ1 rs151344631 pathogenic RCV000148547.1
KCNQ1 rs151344631 pathogenic RCV000030815.2
KCNQ1 rs17215500 pathogenic RCV000003279.2
KCNQ1 rs17221854 pathogenic RCV000003291.2
KCNQ1 rs1800171 pathogenic RCV000045941.3
KCNQ1 rs1800171 pathogenic RCV000003283.2
KCNQ1 rs193922365 pathogenic RCV000030111.1
KCNQ1 rs199472709 pathogenic RCV000046107.3
KCNQ1 rs199472709 pathogenic RCV000115008.2
KCNQ1 rs199472713 pathogenic RCV000046111.3
KCNQ1 rs199472730 pathogenic RCV000046142.3
KCNQ1 rs199472771 likely pathogenic RCV000045968.3
KCNQ1 rs199472776 likely pathogenic RCV000203070.1
KCNQ1 rs199472804 likely pathogenic RCV000046015.3
KCNQ1 rs199473411 likely pathogenic RCV000045959.3
KCNQ1 rs199473460 pathogenic RCV000046131.3
KCNQ1 rs199473471 pathogenic RCV000045943.3
KCNQ1 rs199473480 pathogenic RCV000174453.1
KCNQ1 rs267607197 pathogenic RCV000003296.2
KCNQ1 rs387906290 pathogenic RCV000003282.2
KCNQ1 rs397508070 likely pathogenic RCV000190169.1
KCNQ1 rs397508097 pathogenic RCV000046003.3
KCNQ1 rs397508104 pathogenic RCV000046039.3
KCNQ1 rs397508105 pathogenic RCV000003284.3
KCNQ1 rs397508115 pathogenic RCV000003297.2
KCNQ1 rs397508116 pathogenic RCV000003299.2
KCNQ1 rs587776555 pathogenic RCV000003278.2
KCNQ1 rs794728583 pathogenic RCV000193564.1
KCNQ1 rs796052166 likely pathogenic RCV000190163.1
SCN4B rs121434386 pathogenic RCV000002563.2
SCN5A rs137854600 pathogenic RCV000009971.2
SCN5A rs137854600 pathogenic RCV000009970.4
SCN5A rs137854601 pathogenic RCV000009972.2
SCN5A rs137854605 pathogenic RCV000009982.2
SCN5A rs137854609 pathogenic RCV000009986.2
SCN5A rs137854610 pathogenic RCV000009987.4
SCN5A rs137854614 pathogenic RCV000009969.2
SCN5A rs137854619 pathogenic RCV000010005.2
SCN5A rs199473136 likely pathogenic RCV000171572.1
SCN5A rs199473147 likely pathogenic RCV000171571.1
SCN5A rs199473293 likely pathogenic RCV000190217.1
SCN5A rs199473603 likely pathogenic RCV000148846.1
SCN5A rs28937316 pathogenic RCV000009963.4
SCN5A rs28937317 pathogenic RCV000009964.2
SCN5A rs397514251 pathogenic RCV000009962.3
SCN5A rs397514449 pathogenic RCV000009979.4
SCN5A rs72549410 pathogenic RCV000157478.1
SNTA1 rs121434500 pathogenic RCV000008997.3
SNTA1 rs56157422 pathogenic RCV000191018.2
SNTA1 rs786205426 likely pathogenic RCV000190224.1

Additional Information: