Alternative titles; symbols
ORPHA: 166282; DO: 13884;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3p22.2 | Sick sinus syndrome 1 | 608567 | Autosomal recessive | 3 | SCN5A | 600163 |
A number sign (#) is used with this entry because of evidence that congenital sick sinus syndrome-1 (SSS1) is caused by compound heterozygous mutation in the SCN5A gene (600163) on chromosome 3p22.
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, in which case it is considered to be a congenital disorder (Benson et al., 2003).
Genetic Heterogeneity of Sick Sinus Syndrome
Sick sinus syndrome-2 (SSS2; 163800) is caused by mutation in the HCN4 gene (605206). Susceptibility to sick sinus syndrome-3 (SSS3; 614090) is influenced by variation in the MYH6 gene (160710). Sick sinus syndrome-4 (SSS4; 619464) is caused by mutation in the GNB2 gene (139390).
Ward et al. (1984) described a brother and sister, aged 15 months and 3.5 years, respectively, with atrial standstill and inexcitability. Autopsy in the boy showed endocardial fibroelastosis of atria and ventricles.
Benson et al. (2003) reported 5 children from 3 families with autosomal recessive SSS characterized by sinus bradycardia, absent P waves, atrial inexcitability, prolonged QRS duration, prolonged His-ventricle conduction time, and ventricular escape rhythms. Age of onset was 2 to 9 years, and the disorder progressed from bradycardia to atrial inexcitability during the first decade of life. None of the patients had other evidence of heart disease.
The inheritance pattern of sick sinus syndrome in the families reported by Benson et al. (2003) was autosomal recessive.
In 5 affected children from 3 kindreds with congenital SSS, Benson et al. (2003) identified compound heterozygosity for 6 distinct mutations in the SCN5A gene (e.g., 600163.0025). Heterozygous mutation carriers were asymptomatic, but some showed subclinical evidence of a latent cardiac conduction system disease, particularly first-degree heart block. Benson et al. (2003) noted that 2 of the mutations (e.g., G1408R, 600163.0026) had previously been associated with autosomal dominant disorders of cardiac excitability.
The sick sinus syndrome was originally described by Lown (1967) as a complicating arrhythmia following cardioversion.
Benson, D. W., Wang, D. W., Dyment, M., Knilans, T. K., Fish, F. A., Strieper, M. J., Rhodes, T. H., George, A. L., Jr. Congenital sick sinus syndrome caused by recessive mutations in the cardiac sodium channel gene (SCN5A). J. Clin. Invest. 112: 1019-1028, 2003. [PubMed: 14523039] [Full Text: https://doi.org/10.1172/JCI18062]
Lown, B. Electrical reversion of cardiac arrhythmias. Brit. Heart J. 29: 469-489, 1967. [PubMed: 6029120] [Full Text: https://doi.org/10.1136/hrt.29.4.469]
Nordenberg, A., Varghese, P. J., Nugent, E. W. Spectrum of sinus node dysfunction in two siblings. Am. Heart J. 91: 507-512, 1976. [PubMed: 1258759] [Full Text: https://doi.org/10.1016/s0002-8703(76)80334-1]
Spellberg, R. D. Familial sinus node disease. Chest 60: 246-251, 1971. [PubMed: 5093256] [Full Text: https://doi.org/10.1378/chest.60.3.246]
Ward, D. E., Ho, S. Y., Shinebourne, E. A. Familial atrial standstill and inexcitability in childhood. Am. J. Cardiol. 53: 965-967, 1984. [PubMed: 6702657] [Full Text: https://doi.org/10.1016/0002-9149(84)90540-x]