What is Wolff-Parkinson-White (WPW) syndrome?
Wolff-Parkinson-White is a congenital abnormality resulting in an electrical anomaly in the heart. The physiology of this condition involves the presence of alternative conducting pathway between the atrium and ventricles [1-2]. This alternative pathway (known as an accessory pathway (AP)) acts to conduct faster than normal cardiac impulses and impulses that sometimes conduct in both directions. WPW is associated with distinctive periods of very fast heart beats that originate above the ventricles, otherwise known as supraventricular tachycardia [3].
What causes WPW syndrome?
Figure 1. Normal electrical pathway versus WPW's accessory pathway.
The accessory pathway in WPW syndrome, that connects the atria and the ventricles, allows the heart's electrical signal to bypass the AV node and activate the ventricles too early. This premature electrical impulse can travel around the heart very quickly and are responsible for preexcitation [4].
WPW syndrome affects 1 to 3 per 1,000 persons in the population and is seen in people of all ages, sexes, and ethnicities. The appearance of WPW symptoms is most often seen during infancy and in school-aged children and adolescents. WPW patients may not always experience symptoms and the accessory pathway may spontaneously disappear with age. Clinical studies have shown that males are usually affected by WPW more often than females (2:1 ratio) but the reasoning is still unknown [5].
WPW syndrome affects 1 to 3 per 1,000 persons in the population and is seen in people of all ages, sexes, and ethnicities. The appearance of WPW symptoms is most often seen during infancy and in school-aged children and adolescents. WPW patients may not always experience symptoms and the accessory pathway may spontaneously disappear with age. Clinical studies have shown that males are usually affected by WPW more often than females (2:1 ratio) but the reasoning is still unknown [5].
What is the prkag2 gene?
In a small percentage of cases, WPW is caused by a missense mutation in the prkag2 gene found on the long arm of chromosome 7 [6]. So far, seven different missense mutations have been identified in the prkag2 gene that affect the 5'-AMP-activated protein kinase subunit gamma-2 protein (Accession Number: NP_057287.2) and cause WPW symptoms in patients [7]. Although it is ultimately unknown how the alteration of the 5'-AMP-activated protein kinase subunit gamma-2 (AAKG2) activity causes WPW symptoms, certain research suggests that this alteration causes abnormal build up of glycogen within the heart. Other studies have shown that AMP-activated protein kinase helps regulate the ion channels in the heart that help balance the heart's normal rhythm. Modification to these ion channels may result in an influx of sodium ions that alter the cardiac electrophysiology of the heart and initiate arrythmias [8].
WPW patients most often have no family history of the disease, yet familial WPW does account for a small percentage of occurences. When WPW is familial, the gene mutation appears to have an autosomal dominant pattern of inheritance [6]. Any of the gene mutations that cause familial WPW can be identified through direct DNA genotyping to determine if there is indeed a missense mutation in the region of the prkag2 gene (7q36.1). |
How is WPW syndrome diagnosed?WPW is a disease that can only be diagnosed through the analysis of an electrocardiograph.
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How is WPW syndrome treated?
Figure 5. Radiofrequency catheter ablation of the AP.
There are currently a wide array of different treatments for WPW syndrome. Vagal maneuvers may help to slow tachycardia in WPW patients. These exercises affect the vagus nerve and help regulate heartbeat [4]. Medication such as adenosine, antiarrhythmic drugs, and amidoarone may be prescribed to prevent tachycardiac episodes altogether [9]. If these treatments do not work, some doctors perform electrical cardioversion therapy. This treatment involves electrically shocking the heart in order to affect the heart's electrical impulses and restore a normal rhythm. The most common treatment is the radiofrequency catheter ablation. This procedure involves threading electrical catheters through the blood vessels of the heart in order to damage the accessory pathway and disable it from sending signals. The high success rate and minimally invasive ablation technique prevents the need for surgery in almost all WPW patients [4].
References
[Header Image] Human Cardiovascular System 3D Rendering 02, 2011, BeatMap 3D Animation & Design, Washington DC, accessed 24 Jan. 2013. <http://www.beatmap.net/bmg/wp-content/uploads/2011/08/Beatmap-Human-Cardiovascular-System-3D-Rendering-02.jpg>
[1] Calkins H, Sousa J, el-Atassi R, et al. (1991). Diagnosis and cure of the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardias during a single electrophysiologic test. N Engl J Med,324(23):1612-8. DOI: 10.1056/NEJM199106063242302
[2] Pappone C, Vicedomini G, Manguso F, et al. (2012). Risk of malignant arrhythmias in initially symptomatic patients with Wolff-Parkinson-White syndrome: results of a prospective long-term electrophysiological follow-up study. Circulation, 125(5):661-8. DOI: 10.1161/ CIRCULATIONAHA.111.065722
[3] Cohen, M.I., Triedman, J., Cannon, B., et al. (2012). PACES/HRS Expert Consensus Statement on the Mangagement of the Asymptomatic Young Patient with a Wolff-Parkinson-White (WPW, Ventricular Preexcitation) Electrocardiographic Pattern. Heart Rhythm, 9(6): 1006-24. DOI: 10.1016/j.hrthm.2012.03.050.
[4] http://www.mayoclinic.com/health/wolff-parkinson-white-syndrome/DS00923
[5] http://equimedcorp.com/rhythms/topic/53/
[6] Gollob, M.H., Green, M., Tang, A., et al. (2001). Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N Engl J Med, 344, 1823-31. doi: 10.1056/NEJM200106143442403
[7] http://ghr.nlm.nih.gov/gene/PRKAG2
[8] LIGHT, P. E. (2006), Familial Wolff-Parkinson-White Syndrome: A Disease of Glycogen Storage or Ion Channel Dysfunction?. Journal of Cardiovascular Electrophysiology, 17: S158–S161. DOI: 10.1111/j.1540-8167.2006.00399.x
[9] Olgin J, Zipes DP. Specific arrhythmias: diagnosis and treatment. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 39.
[1] Calkins H, Sousa J, el-Atassi R, et al. (1991). Diagnosis and cure of the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardias during a single electrophysiologic test. N Engl J Med,324(23):1612-8. DOI: 10.1056/NEJM199106063242302
[2] Pappone C, Vicedomini G, Manguso F, et al. (2012). Risk of malignant arrhythmias in initially symptomatic patients with Wolff-Parkinson-White syndrome: results of a prospective long-term electrophysiological follow-up study. Circulation, 125(5):661-8. DOI: 10.1161/ CIRCULATIONAHA.111.065722
[3] Cohen, M.I., Triedman, J., Cannon, B., et al. (2012). PACES/HRS Expert Consensus Statement on the Mangagement of the Asymptomatic Young Patient with a Wolff-Parkinson-White (WPW, Ventricular Preexcitation) Electrocardiographic Pattern. Heart Rhythm, 9(6): 1006-24. DOI: 10.1016/j.hrthm.2012.03.050.
[4] http://www.mayoclinic.com/health/wolff-parkinson-white-syndrome/DS00923
[5] http://equimedcorp.com/rhythms/topic/53/
[6] Gollob, M.H., Green, M., Tang, A., et al. (2001). Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N Engl J Med, 344, 1823-31. doi: 10.1056/NEJM200106143442403
[7] http://ghr.nlm.nih.gov/gene/PRKAG2
[8] LIGHT, P. E. (2006), Familial Wolff-Parkinson-White Syndrome: A Disease of Glycogen Storage or Ion Channel Dysfunction?. Journal of Cardiovascular Electrophysiology, 17: S158–S161. DOI: 10.1111/j.1540-8167.2006.00399.x
[9] Olgin J, Zipes DP. Specific arrhythmias: diagnosis and treatment. In: Bonow RO, Mann DL, Zipes DP, Libby P, eds. Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine. 9th ed. Philadelphia, Pa: Saunders Elsevier; 2011:chap 39.
Margaret Beatka ([email protected])
Page Last Updated: 5/10/13
This web page was produced as an assignment for Genetics 677, as an undergraduate course at UW-Madison.
Page Last Updated: 5/10/13
This web page was produced as an assignment for Genetics 677, as an undergraduate course at UW-Madison.