Sick Sinus Syndrome 3, Susceptibility To
A number sign (#) is used with this entry because of evidence that susceptibility to sick sinus syndrome-3 (SSS3) results from variation in the MYH6 gene (160710) on chromosome 14q11.
DescriptionSick sinus syndrome may be encountered at any age but is primarily a disease of the elderly and is often secondary to other cardiac disorders when diagnosed in younger individuals. Symptoms are often intermittent and/or nonspecific and include dizziness, syncope, and heart failure. The only effective treatment for symptomatic and irreversible sinus node dysfunction is permanent cardiac pacing, and sick sinus syndrome remains the most common indication for permanent pacemaker implantation (summary by Holm et al., 2011).
For a general phenotypic description and a discussion of genetic heterogeneity of sick sinus syndrome, see SSS1 (608567).
Molecular GeneticsThrough complementary application of SNP genotyping, whole genome sequencing, and imputation in 38,384 Icelanders, Holm et al. (2011) identified MYH6 as a previously unidentified sick sinus syndrome susceptibility gene. A missense variant in this gene (160710.0008), arg721 to trp (2161C-T), has an allelic frequency of 0.38% in Icelanders and associates with sick sinus syndrome with an odds ratio of 12.53 (p = 1.5 x 10(-29)). Holm et al. (2011) showed that the lifetime risk of being diagnosed with sick sinus syndrome is around 6% for noncarriers of this variant but is approximately 50% for carriers of the variant. In controls, the 2161C-T variant associated with slower heart rate and longer PR interval.