Familial sick sinus syndrome

MedGen UID:: 573766
•Concept ID:: C0340491
•: Disease or Syndrome

Synonyms:	familial sick sinus syndrome; familial sinus node dysfunction; hereditary sick sinus syndrome; sick sinus syndrome 1, autosomal recessive; SSS1
SNOMED CT:	Familial sick sinus syndrome (233913007)
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Autosomal dominant inheritance MedGen UID: 141047 •Concept ID: C0443147 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele. Autosomal recessive inheritance (Orphanet) Autosomal dominant inheritance (Orphanet)

Related genes: Gene(s) associated with related conditions. For conditions in a hierarchy, the parent condition will list the genes associated with the children conditions.	HCN4, SCN5A, MYH6

Monarch Initiative:	MONDO:0012061
OMIM® Phenotypic series:	PS608567
Orphanet:	ORPHA166282

Definition

A rare cardiac rhythm disease, usually of the elderly, characterized by electrocardiographic findings of sinus bradycardia, atrial fibrillation, atrial tachycardia sinus arrest, or sino-atrial block, and that manifest with symptoms like syncope, dizziness, palpitations, fatigue, or even heart failure. It results from malfunction of the cardiac conduction system, probably secondary to degenerative fibrosis of nodal tissue in the elderly or secondary to cardiac disorders in younger patients. [from ORDO]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVSick sinus syndrome
- Familial sick sinus syndrome

Disorder of cardiovascular system
- Abnormality of the cardiovascular system
  - Abnormal cardiovascular system physiology
    - Abnormality of cardiovascular system electrophysiology
      - Cardiac arrhythmia
        Genetic cardiac rhythm disease
        Familial sick sinus syndrome
        Sick sinus syndrome 1
        Sick sinus syndrome 2, autosomal dominant
        Sick sinus syndrome 3, susceptibility to

Professional guidelines

PubMed

Primary Ciliary Dyskinesia: First Health-related Quality-of-Life Measures for Pediatric Patients.

Dell SD, Leigh MW, Lucas JS, Ferkol TW, Knowles MR, Alpern A, Behan L, Morris AM, Hogg C, DunnGalvin A, Quittner AL
Ann Am Thorac Soc 2016 Oct;13(10):1726-1735. doi: 10.1513/AnnalsATS.201603-198OC. PMID: 27464304 Free PMC Article

Evaluation of the Genetic Basis of Familial Aggregation of Pacemaker Implantation by a Large Next Generation Sequencing Panel.

Celestino-Soper PB, Doytchinova A, Steiner HA, Uradu A, Lynnes TC, Groh WJ, Miller JM, Lin H, Gao H, Wang Z, Liu Y, Chen PS, Vatta M
PLoS One 2015;10(12):e0143588. Epub 2015 Dec 4 doi: 10.1371/journal.pone.0143588. PMID: 26636822 Free PMC Article

High-efficiency multiplex capillary electrophoresis single strand conformation polymorphism (multi-CE-SSCP) mutation screening of SCN5A: a rapid genetic approach to cardiac arrhythmia.

Hofman-Bang J, Behr ER, Hedley P, Tfelt-Hansen J, Kanters JK, Haunsøe S, McKenna WJ, Christiansen M
Clin Genet 2006 Jun;69(6):504-11. doi: 10.1111/j.1399-0004.2006.00621.x. PMID: 16712702

See all (3)

Recent clinical studies

Etiology

Cardiac Emerinopathy: A Nonsyndromic Nuclear Envelopathy With Increased Risk of Thromboembolic Stroke Due to Progressive Atrial Standstill and Left Ventricular Noncompaction.

Ishikawa T, Mishima H, Barc J, Takahashi MP, Hirono K, Terada S, Kowase S, Sato T, Mukai Y, Yui Y, Ohkubo K, Kimoto H, Watanabe H, Hata Y, Aiba T, Ohno S, Chishaki A, Shimizu W, Horie M, Ichida F, Nogami A, Yoshiura KI, Schott JJ, Makita N
Circ Arrhythm Electrophysiol 2020 Oct;13(10):e008712. Epub 2020 Jul 29 doi: 10.1161/CIRCEP.120.008712. PMID: 32755394

Transforming Growth Factor-β1 T869C Gene Polymorphism Is Associated with Acquired Sick Sinus Syndrome via Linking a Higher Serum Protein Level.

Chen JY, Liu JH, Wu HD, Lin KH, Chang KC, Liou YM
PLoS One 2016;11(7):e0158676. Epub 2016 Jul 5 doi: 10.1371/journal.pone.0158676. PMID: 27380173 Free PMC Article

Multiple loss-of-function mechanisms contribute to SCN5A-related familial sick sinus syndrome.

Gui J, Wang T, Jones RP, Trump D, Zimmer T, Lei M
PLoS One 2010 Jun 7;5(6):e10985. doi: 10.1371/journal.pone.0010985. PMID: 20539757 Free PMC Article

See all (3)

Diagnosis

Whole genome sequencing identifies a deletion mutation in the unknown-functional KCNG2 from familial sick sinus syndrome.

Sun C, Li N, Wang QQ, Yan LY, Ba SK, Zhang SS, He QX, Chen XQ, Gong WL, Zhu Q, Liu KC
Physiol Genomics 2022 Apr 1;54(4):141-152. Epub 2022 Mar 14 doi: 10.1152/physiolgenomics.00132.2021. PMID: 35285753

Sick sinus syndrome with HCN4 mutations shows early onset and frequent association with atrial fibrillation and left ventricular noncompaction.

Ishikawa T, Ohno S, Murakami T, Yoshida K, Mishima H, Fukuoka T, Kimoto H, Sakamoto R, Ohkusa T, Aiba T, Nogami A, Sumitomo N, Shimizu W, Yoshiura KI, Horigome H, Horie M, Makita N
Heart Rhythm 2017 May;14(5):717-724. Epub 2017 Jan 17 doi: 10.1016/j.hrthm.2017.01.020. PMID: 28104484

Sodium channelopathy underlying familial sick sinus syndrome with early onset and predominantly male characteristics.

Abe K, Machida T, Sumitomo N, Yamamoto H, Ohkubo K, Watanabe I, Makiyama T, Fukae S, Kohno M, Harrell DT, Ishikawa T, Tsuji Y, Nogami A, Watabe T, Oginosawa Y, Abe H, Maemura K, Motomura H, Makita N
Circ Arrhythm Electrophysiol 2014 Jun;7(3):511-7. Epub 2014 Apr 24 doi: 10.1161/CIRCEP.113.001340. PMID: 24762805

A novel SCN5A mutation demonstrating a variety of clinical phenotypes in familial sick sinus syndrome.

Nakajima S, Makiyama T, Hanazawa K, Kaitani K, Amano M, Hayama Y, Onishi N, Tamaki Y, Miyake M, Tamura T, Kondo H, Motooka M, Izumi C, Nakagawa Y, Horie M
Intern Med 2013;52(16):1805-8. Epub 2012 Mar 1 doi: 10.2169/internalmedicine.52.0085. PMID: 23955615

Sudden cardiac death and inherited arrhythmia syndromes.

Sarkozy A, Brugada P
J Cardiovasc Electrophysiol 2005 Sep;16 Suppl 1:S8-20. doi: 10.1111/j.1540-8167.2005.50110.x. PMID: 16138889

See all (7)

Prognosis

Novel mutation in the α-myosin heavy chain gene is associated with sick sinus syndrome.

Ishikawa T, Jou CJ, Nogami A, Kowase S, Arrington CB, Barnett SM, Harrell DT, Arimura T, Tsuji Y, Kimura A, Makita N
Circ Arrhythm Electrophysiol 2015 Apr;8(2):400-8. Epub 2015 Feb 25 doi: 10.1161/CIRCEP.114.002534. PMID: 25717017

Sodium channelopathy underlying familial sick sinus syndrome with early onset and predominantly male characteristics.

See all (2)