SSS2
MCID: SCK014
MIFTS: 29

Sick Sinus Syndrome 2 (SSS2)

Categories: Cardiovascular diseases, Genetic diseases, Muscle diseases, Rare diseases

Aliases & Classifications for Sick Sinus Syndrome 2

MalaCards integrated aliases for Sick Sinus Syndrome 2:

Name: Sick Sinus Syndrome 2 57 72 13
Sick Sinus Syndrome 2, Autosomal Dominant 29 6 70
Sick Sinus Syndrome 2 with or Without Cardiac Noncompaction and/or Ascending Aorta Dilation 57 72
Sinus Bradycardia Syndrome, Familial, Autosomal Dominant 57 72
Sinus Node Disease, Familial, Autosomal Dominant 57 72
Atrial Fibrillation with Bradyarrhythmia 57 72
Sss2 57 72
Familial Sinus Bradycardia Syndrome Autosomal Dominant 72
Sinus, Sick, Syndrome, Type 2, Autosomal Dominant 39
Autosomal Dominant Sick Sinus Syndrome 2 72
Sss Autosomal Dominant 72

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal dominant

Miscellaneous:
onset in utero or at birth


HPO:

31
sick sinus syndrome 2:
Inheritance autosomal dominant inheritance
Onset and clinical course congenital onset


Classifications:



External Ids:

OMIM® 57 163800
OMIM Phenotypic Series 57 PS608567
MedGen 41 C1834144
UMLS 70 C1834144

Summaries for Sick Sinus Syndrome 2

UniProtKB/Swiss-Prot : 72 Sick sinus syndrome 2: The term 'sick sinus syndrome' encompasses a variety of conditions caused by sinus node dysfunction. The most common clinical manifestations are syncope, presyncope, dizziness, and fatigue. Electrocardiogram typically shows sinus bradycardia, sinus arrest, and/or sinoatrial block. Episodes of atrial tachycardias coexisting with sinus bradycardia ('tachycardia-bradycardia syndrome') are also common in this disorder. SSS occurs most often in the elderly associated with underlying heart disease or previous cardiac surgery, but can also occur in the fetus, infant, or child without heart disease or other contributing factors. SSS2 onset is in utero or at birth.

MalaCards based summary : Sick Sinus Syndrome 2, also known as sick sinus syndrome 2, autosomal dominant, is related to sick sinus syndrome and atrioventricular block. An important gene associated with Sick Sinus Syndrome 2 is HCN4 (Hyperpolarization Activated Cyclic Nucleotide Gated Potassium Channel 4). Affiliated tissues include heart, and related phenotypes are mitral valve prolapse and left ventricular hypertrophy

More information from OMIM: 163800 PS608567

Related Diseases for Sick Sinus Syndrome 2

Diseases in the Sick Sinus Syndrome family:

Sick Sinus Syndrome 2 Sick Sinus Syndrome 1
Sick Sinus Syndrome 3 Familial Sick Sinus Syndrome

Diseases related to Sick Sinus Syndrome 2 via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 sick sinus syndrome 10.1
2 atrioventricular block 10.1
3 syncope 10.1

Symptoms & Phenotypes for Sick Sinus Syndrome 2

Human phenotypes related to Sick Sinus Syndrome 2:

31 (show all 9)
# Description HPO Frequency HPO Source Accession
1 mitral valve prolapse 31 occasional (7.5%) HP:0001634
2 left ventricular hypertrophy 31 occasional (7.5%) HP:0001712
3 aortic regurgitation 31 occasional (7.5%) HP:0001659
4 cardiac arrest 31 occasional (7.5%) HP:0001695
5 ventricular fibrillation 31 occasional (7.5%) HP:0001663
6 left ventricular noncompaction 31 occasional (7.5%) HP:0030682
7 atrial fibrillation 31 HP:0005110
8 sick sinus syndrome 31 HP:0011704
9 sinus bradycardia 31 HP:0001688

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Cardiovascular Heart:
sinus bradycardia
left ventricular hypertrophy (in some patients)
atrial fibrillation (in some patients)
ventricular fibrillation (in some patients)
cardiac arrest (rare)
more
Cardiovascular Vascular:
dilation of ascending aorta (in some patients)

Clinical features from OMIM®:

163800 (Updated 20-May-2021)

Drugs & Therapeutics for Sick Sinus Syndrome 2

Search Clinical Trials , NIH Clinical Center for Sick Sinus Syndrome 2

Genetic Tests for Sick Sinus Syndrome 2

Genetic tests related to Sick Sinus Syndrome 2:

# Genetic test Affiliating Genes
1 Sick Sinus Syndrome 2, Autosomal Dominant 29 HCN4

Anatomical Context for Sick Sinus Syndrome 2

MalaCards organs/tissues related to Sick Sinus Syndrome 2:

40
Heart

Publications for Sick Sinus Syndrome 2

Articles related to Sick Sinus Syndrome 2:

(show all 34)
# Title Authors PMID Year
1
Dilation of the Aorta Ascendens Forms Part of the Clinical Spectrum of HCN4 Mutations. 57 6
27173043 2016
2
The symptom complex of familial sinus node dysfunction and myocardial noncompaction is associated with mutations in the HCN4 channel. 57 6
25145518 2014
3
HCN4 mutations in multiple families with bradycardia and left ventricular noncompaction cardiomyopathy. 57 6
25145517 2014
4
cAMP sensitivity of HCN pacemaker channels determines basal heart rate but is not critical for autonomic rate control. 57 6
20693575 2010
5
Point mutation in the HCN4 cardiac ion channel pore affecting synthesis, trafficking, and functional expression is associated with familial asymptomatic sinus bradycardia. 57 6
17646576 2007
6
Familial sinus bradycardia associated with a mutation in the cardiac pacemaker channel. 57 6
16407510 2006
7
Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. 6 57
15123648 2004
8
Pacemaker channel dysfunction in a patient with sinus node disease. 57 6
12750403 2003
9
Familial idiopathic atrial fibrillation with bradyarrhythmia. 57
8750801 1996
10
[Familial idiopathic atrial fibrillation with bradyarrhythmia]. 57
8291288 1993
11
Follow-up of the family with congenital absence of sinus rhythm. 57
3341232 1988
12
Sinus node disease affecting both parents and both children. 57
477701 1979
13
Familial sinus node dysfunction with autosomal dominant inheritance. 57
718774 1978
14
Familial sinoatrial node dysfunction. Increased vagal tone a possible aetiology. 57
971377 1976
15
Congenital familial nodal rhythm. 57
13685714 1960
16
Three STIGMA AND STYLE STYLISTs Pattern the Fine Architectures of Apical Gynoecium and Are Critical for Male Gametophyte-Pistil Interaction. 61
33007250 2020
17
Oral hygiene practices and utilization of oral healthcare services among in-school adolescents in Calabar, Cross River State, Nigeria. 61
33117494 2020
18
Prognostic value of myocardium perfusion imaging with a new reconstruction algorithm. 61
24281904 2014
19
Effect of pimobendan in addition to standard therapy for heart failure on prevention of readmission in elderly patients with severe chronic heart failure. 61
23581555 2014
20
[Pacemaker infection developed one month after the surgery for prosthetic valve endocarditis]. 61
22374599 2012
21
Local drug delivery system for the treatment of osteomyelitis: In vitro evaluation. 61
21126218 2011
22
Initial and delayed stress phase imaging in a single-injection double-acquisition SPECT. The potential value of early 99mTc-MIBI redistribution in assessment of myocardial perfusion reversibility in patients with coronary artery disease. 61
20162245 2010
23
Bacterial reduction of selenate to elemental selenium utilizing molasses as a carbon source. 61
17512724 2008
24
Microwave and radiofrequency ablation yield similar success rates for treatment of chronic atrial fibrillation. 61
15145003 2004
25
Noninvasive transthoracic temporary cardiac pacing in dogs. 61
14529132 2003
26
Transvenous permanent pacemaker implantation in children and adolescent. 61
11811224 2001
27
Expression of the S1 and S2 subunits of murine coronavirus JHMV spike protein by a vaccinia virus transient expression system. 61
8245853 1993
28
[Echocardiography-guided temporary implantation of electrode catheters: an alternative with reliable results even during prolonged use]. 61
1389304 1992
29
Postextrasystolic sinoatrial exit block in human sick sinus syndrome: demonstration by direct recording of sinus node electrograms. 61
1720277 1991
30
[Carotid sinus syndrome and sick sinus syndrome: 2 frequent and distinct indications for pacemaker implantation]. 61
2328858 1990
31
Rate responsive pacing using a minute ventilation sensor. 61
2463560 1988
32
Modified Shumacker repair of transposition of the great arteries. Surgical and angiocardiographic considerations. 61
6823149 1983
33
[Transvenous pacemaker implantations for sick sinus syndrome (2 cases) complicating with persistent left superior vena cava (author's transl)]. 61
7382214 1980
34
Clinical studies on the sick sinus syndrome. 61
1271572 1976

Variations for Sick Sinus Syndrome 2

ClinVar genetic disease variations for Sick Sinus Syndrome 2:

6 (show top 50) (show all 93)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HCN4 NM_005477.3(HCN4):c.1438G>C (p.Gly480Arg) SNV Pathogenic 5176 rs121908411 GRCh37: 15:73622066-73622066
GRCh38: 15:73329725-73329725
2 HCN4 NM_005477.3(HCN4):c.1441T>C (p.Tyr481His) SNV Pathogenic 374860 rs1057519275 GRCh37: 15:73622063-73622063
GRCh38: 15:73329722-73329722
3 HCN4 NM_005477.3(HCN4):c.1920_1932dup (p.Lys645fs) Duplication Pathogenic 374858 rs1057519274 GRCh37: 15:73617341-73617342
GRCh38: 15:73325000-73325001
4 HCN4 NM_005477.3(HCN4):c.1241C>G (p.Ala414Gly) SNV Pathogenic 374861 rs1057519276 GRCh37: 15:73624602-73624602
GRCh38: 15:73332261-73332261
5 HCN4 NM_005477.3(HCN4):c.1444G>C (p.Gly482Arg) SNV Pathogenic 374859 rs794727637 GRCh37: 15:73622060-73622060
GRCh38: 15:73329719-73329719
6 HCN4 NM_005477.3(HCN4):c.2016C>A (p.Ser672Arg) SNV Pathogenic 5173 rs104894488 GRCh37: 15:73616557-73616557
GRCh38: 15:73324216-73324216
7 HCN4 NM_005477.3(HCN4):c.1631del (p.Pro544fs) Deletion Pathogenic 5174 rs1057519015 GRCh37: 15:73617745-73617745
GRCh38: 15:73325404-73325404
8 HCN4 NM_005477.3(HCN4):c.1657G>A (p.Asp553Asn) SNV Uncertain significance 5175 rs104894485 GRCh37: 15:73617719-73617719
GRCh38: 15:73325378-73325378
9 HCN4 NM_005477.3(HCN4):c.*592G>A SNV Uncertain significance 884690 GRCh37: 15:73614230-73614230
GRCh38: 15:73321889-73321889
10 HCN4 NM_005477.3(HCN4):c.*2585G>A SNV Uncertain significance 885564 GRCh37: 15:73612237-73612237
GRCh38: 15:73319896-73319896
11 HCN4 NM_005477.3(HCN4):c.*168A>G SNV Uncertain significance 884692 GRCh37: 15:73614654-73614654
GRCh38: 15:73322313-73322313
12 HCN4 NM_005477.3(HCN4):c.*2241T>C SNV Uncertain significance 885569 GRCh37: 15:73612581-73612581
GRCh38: 15:73320240-73320240
13 HCN4 NM_005477.3(HCN4):c.*44C>T SNV Uncertain significance 885635 GRCh37: 15:73614778-73614778
GRCh38: 15:73322437-73322437
14 HCN4 NM_005477.3(HCN4):c.3218C>T (p.Pro1073Leu) SNV Uncertain significance 538077 rs982016034 GRCh37: 15:73615216-73615216
GRCh38: 15:73322875-73322875
15 HCN4 NM_005477.3(HCN4):c.3205C>T (p.Arg1069Trp) SNV Uncertain significance 840097 GRCh37: 15:73615229-73615229
GRCh38: 15:73322888-73322888
16 HCN4 NM_005477.3(HCN4):c.3130C>T (p.Arg1044Trp) SNV Uncertain significance 580858 rs553950644 GRCh37: 15:73615304-73615304
GRCh38: 15:73322963-73322963
17 HCN4 NM_005477.3(HCN4):c.3305G>A (p.Arg1102His) SNV Uncertain significance 579697 rs548130184 GRCh37: 15:73615129-73615129
GRCh38: 15:73322788-73322788
18 HCN4 NM_005477.3(HCN4):c.2917G>A (p.Gly973Arg) SNV Uncertain significance 570199 rs200495478 GRCh37: 15:73615517-73615517
GRCh38: 15:73323176-73323176
19 HCN4 NM_005477.3(HCN4):c.1297G>A (p.Gly433Ser) SNV Uncertain significance 470646 rs573588965 GRCh37: 15:73624546-73624546
GRCh38: 15:73332205-73332205
20 HCN4 NM_005477.3(HCN4):c.418G>A (p.Gly140Ser) SNV Uncertain significance 190786 rs773857091 GRCh37: 15:73660194-73660194
GRCh38: 15:73367853-73367853
21 HCN4 NM_005477.3(HCN4):c.*767C>T SNV Uncertain significance 884687 GRCh37: 15:73614055-73614055
GRCh38: 15:73321714-73321714
22 HCN4 NM_005477.3(HCN4):c.*104A>T SNV Uncertain significance 884694 GRCh37: 15:73614718-73614718
GRCh38: 15:73322377-73322377
23 HCN4 NM_005477.3(HCN4):c.577G>T (p.Gly193Cys) SNV Uncertain significance 885695 GRCh37: 15:73660035-73660035
GRCh38: 15:73367694-73367694
24 HCN4 NM_005477.3(HCN4):c.522G>A (p.Pro174=) SNV Uncertain significance 885696 GRCh37: 15:73660090-73660090
GRCh38: 15:73367749-73367749
25 HCN4 NM_005477.3(HCN4):c.375C>T (p.Ser125=) SNV Uncertain significance 885697 GRCh37: 15:73660237-73660237
GRCh38: 15:73367896-73367896
26 HCN4 NM_005477.3(HCN4):c.319G>A (p.Gly107Ser) SNV Uncertain significance 885698 GRCh37: 15:73660293-73660293
GRCh38: 15:73367952-73367952
27 HCN4 NM_005477.3(HCN4):c.*2010A>C SNV Uncertain significance 886589 GRCh37: 15:73612812-73612812
GRCh38: 15:73320471-73320471
28 HCN4 NM_005477.3(HCN4):c.*1834G>T SNV Uncertain significance 886591 GRCh37: 15:73612988-73612988
GRCh38: 15:73320647-73320647
29 HCN4 NM_005477.3(HCN4):c.*1598A>G SNV Uncertain significance 886593 GRCh37: 15:73613224-73613224
GRCh38: 15:73320883-73320883
30 HCN4 NM_005477.3(HCN4):c.*1205A>G SNV Uncertain significance 886596 GRCh37: 15:73613617-73613617
GRCh38: 15:73321276-73321276
31 HCN4 NM_005477.3(HCN4):c.3081C>T (p.Pro1027=) SNV Uncertain significance 886650 GRCh37: 15:73615353-73615353
GRCh38: 15:73323012-73323012
32 HCN4 NM_005477.3(HCN4):c.-114G>A SNV Uncertain significance 886704 GRCh37: 15:73660725-73660725
GRCh38: 15:73368384-73368384
33 HCN4 NM_005477.3(HCN4):c.-132G>C SNV Uncertain significance 886705 GRCh37: 15:73660743-73660743
GRCh38: 15:73368402-73368402
34 HCN4 NM_005477.3(HCN4):c.-188G>T SNV Uncertain significance 886706 GRCh37: 15:73660799-73660799
GRCh38: 15:73368458-73368458
35 HCN4 NM_005477.3(HCN4):c.2917G>A (p.Gly973Arg) SNV Uncertain significance 570199 rs200495478 GRCh37: 15:73615517-73615517
GRCh38: 15:73323176-73323176
36 HCN4 NM_005477.3(HCN4):c.-364C>G SNV Uncertain significance 886707 GRCh37: 15:73660975-73660975
GRCh38: 15:73368634-73368634
37 HCN4 NM_005477.3(HCN4):c.-497G>A SNV Uncertain significance 886708 GRCh37: 15:73661108-73661108
GRCh38: 15:73368767-73368767
38 HCN4 NM_005477.3(HCN4):c.*1085A>C SNV Uncertain significance 887844 GRCh37: 15:73613737-73613737
GRCh38: 15:73321396-73321396
39 HCN4 NM_005477.3(HCN4):c.*980C>T SNV Uncertain significance 887845 GRCh37: 15:73613842-73613842
GRCh38: 15:73321501-73321501
40 HCN4 NM_005477.3(HCN4):c.*901C>T SNV Uncertain significance 887846 GRCh37: 15:73613921-73613921
GRCh38: 15:73321580-73321580
41 HCN4 NM_005477.3(HCN4):c.*847A>G SNV Uncertain significance 887847 GRCh37: 15:73613975-73613975
GRCh38: 15:73321634-73321634
42 HCN4 NM_005477.3(HCN4):c.*1172A>G SNV Uncertain significance 887842 GRCh37: 15:73613650-73613650
GRCh38: 15:73321309-73321309
43 HCN4 NM_005477.3(HCN4):c.2314G>A (p.Val772Ile) SNV Uncertain significance 887898 GRCh37: 15:73616120-73616120
GRCh38: 15:73323779-73323779
44 HCN4 NM_005477.3(HCN4):c.2175C>G (p.Val725=) SNV Uncertain significance 887899 GRCh37: 15:73616259-73616259
GRCh38: 15:73323918-73323918
45 HCN4 NM_005477.3(HCN4):c.2143+8G>A SNV Uncertain significance 887900 GRCh37: 15:73616422-73616422
GRCh38: 15:73324081-73324081
46 HCN4 NM_005477.3(HCN4):c.1844T>G (p.Val615Gly) SNV Uncertain significance 887901 GRCh37: 15:73617430-73617430
GRCh38: 15:73325089-73325089
47 HCN4 NM_005477.3(HCN4):c.249C>T (p.Gly83=) SNV Uncertain significance 511427 rs1183278712 GRCh37: 15:73660363-73660363
GRCh38: 15:73368022-73368022
48 HCN4 NM_005477.3(HCN4):c.458A>G (p.Glu153Gly) SNV Uncertain significance 180370 rs560874115 GRCh37: 15:73660154-73660154
GRCh38: 15:73367813-73367813
49 HCN4 NM_005477.3(HCN4):c.-518A>G SNV Uncertain significance 887957 GRCh37: 15:73661129-73661129
GRCh38: 15:73368788-73368788
50 HCN4 NM_005477.3(HCN4):c.-529G>A SNV Uncertain significance 887958 GRCh37: 15:73661140-73661140
GRCh38: 15:73368799-73368799

UniProtKB/Swiss-Prot genetic disease variations for Sick Sinus Syndrome 2:

72
# Symbol AA change Variation ID SNP ID
1 HCN4 p.Asp553Asn VAR_026534 rs104894485
2 HCN4 p.Ser672Arg VAR_026535 rs104894488
3 HCN4 p.Ala485Val VAR_066614 rs145474870

Expression for Sick Sinus Syndrome 2

Search GEO for disease gene expression data for Sick Sinus Syndrome 2.

Pathways for Sick Sinus Syndrome 2

GO Terms for Sick Sinus Syndrome 2

Sources for Sick Sinus Syndrome 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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