Sick sinus syndrome

Definition:

Sick sinus syndrome (SSS) comprises a variety of conditions involving sinus node dysfunction and commonly affects elderly persons. Patients may experience syncope, pre-syncope, palpitations, or dizziness. SSS has multiple manifestations on electrocardiogram, including sinus bradycardia, sinus arrest, sinoatrial block, and alternating patterns of bradycardia and tachycardia. Autosomal recessive type (SSS1) can be caused by compound heterozygous mutation in the SCN5A gene, and autosomal dominant type (SSS2) can be caused by heterozygous mutation in the HCN4. SCN5A encodes an alpha-subunit of the cardiac sodium channel carrying the current to form a rapid upstroke of action potential, whereas HCN4 codes for an alpha-subunit of hyperpolarization-activated cation channel.

References:

[1]. Birgit Stallmeyer, et al. A Mutation in the G-Protein Gene GNB2 Causes Familial Sinus Node and Atrioventricular Conduction Dysfunction. Circ Res. 2017 May 12;120(10):e33-e44. [Content Brief]

[2]. D Woodrow Benson, et al. Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J Clin Invest. 2003 Oct;112(7):1019-28. [Content Brief]

[3]. Hilma Holm, et al. A rare variant in MYH6 is associated with high risk of sick sinus syndrome. Nat Genet. 2011 Mar 6;43(4):316-20. [Content Brief]

[4]. Kazuo Ueda, et al. Functional characterization of a trafficking-defective HCN4 mutation, D553N, associated with cardiac arrhythmia. J Biol Chem. 2004 Jun 25;279(26):27194-8. [Content Brief]

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