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Genetic basis and pathogenesis of Familial WPW Syndrome

Sidhu, Jasvinder and Roberts, Robert (2003) Genetic basis and pathogenesis of Familial WPW Syndrome. [Journal (Paginated)]

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Abstract

The Wolff-Parkinson-White (WPW) syndrome has been a known clinical entity for over fifty years. In 1967 Durrer et al postulated WPW syndrome was due to an accessory pathway, bypassing the AV node, from the atria to the ventricles1. This was later confirmed by epicardial mapping. WPW is the second most common cause of paroxysmal supraventricular tachycardias in the western world and the most common cause in China2. WPW syndrome has a prevalence of 1.5 to 3.1 per 1000 persons in western countries3,4,5 . Patients with the WPW syndrome may present with palpitations, presyncope, syncope, or sudden cardiac death (SCD). In some patients the first and only manifestation of the disease is SCD. This is more likely to occur in the setting of atrial fibrillation with a rapid ventricular response. Electrocardiographic findings of WPW syndrome consist of preexcitation manifested by a shortened PR interval (<120 msec), a widened QRS (>100 msec) a delta wave (abnormal initial QRS vector) and supraventricular tachycardia. The EKG finding of preexcitation is a result of early ventricular depolarization through the accessory pathway. SVT can occur with retrograde or antigrade conduction through the accessory pathway forming the basis of the so-called “macro-reentrant” arrhythmia model 6. Rapid conduction through the accessory pathway in the setting of atrial fibrillation markedly increases the risk of SCD7. We recently identified the gene responsible for familial Wolff-Parkinson-White 8. The gene (PRKAG2) which encodes for a protein AMPK (AMP- activated protein kinase) was identified as the causal gene. Missense (single nucleotide change) mutations in this gene were identified in families with WPW. Six such mutations have been identified. Along with preexcitation the affected families had conduction abnormalities (AV block) and cardiac hypertrophy.

Item Type:Journal (Paginated)
Keywords:WPW syndrome; genetic basis
Subjects:JOURNALS > Indian Pacing and Electrophysiology Journal
ID Code:4243
Deposited By:Indian Pacing and Electrophysiology, Journal
Deposited On:20 Apr 2005
Last Modified:11 Mar 2011 08:55

References in Article

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1. Durrer D., Roos JP. Epicardial excitation of the ventricles in a patient with a Wolff-Parkinson White syndrome (type B). Circulation. 1967, 35: 15-21.

2. Wan Q, Wu N, Fan W, Tang YY, Jin L, FangQ. Clinical manifestations and prevalence of different types of supraventricular tachycardia among Chinese. Chin Med J (Engl) 1992, 105: 284-8.

3. Packard JM, Graettinger JS, Graybeil A. Analysis of the electrocardiograms obtained from 1000 young healthy aviators: ten year follow-up. Circulation 1954, 10: 384-400.

4. Hejtmancik MR, Hermann GR. The electrocardiographic syndrome of short PR interval and board QRS complexs: a clinical study of 80 cases. Am Heart J 1957, 54: 708-21.

5. Guize L, Soria R, Chaouat JC, Chretien JM, Houe D, Le Heuzey JY. Prevalence et evolution du syndrome de Wolff-Parkinson-Syndrome dans une population de 138 048 sujets. Ann Med Interne 1985, 136: 474-8.

6. Kastor JA, Goldreyer BN, Moore EN, Spear JF. Re-entry – an important mechanism of cardiac arrhythmias. Cardiovasc Clin 1974, 6: 111-35.

7. Wiedermann CJ, Becker AE, Hopferwieser T, et. al. Sudden death in a young competitive athlete with Wolff-Parkinson-White syndrome. Eur. Heart J 1987, 8:

651-655.

8. Gollub MH et al. Identification of a gene responsible for familial Wolff- Parkinson-White Syndrome. NEJM 2001, 344: 1823-1831.

9. Cheung PC, Salt IP, Davies DG, et al. Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding. Biochem J 2000, 346: 659-669.

10. Hardie, Carling. The AMP-activated protein kinase--fuel gauge of the mammalian cell? Eur J Biochem 1997, 246: 259-273.

11. Gollob MH, Green MS, Tang AS, and Robert R. PRKAG2 cardiac syndrome: familial ventricular preexcitation, conduction system disease, and cardiac hypertrophy Curr Opin Cardiol 2002, 17: 229-234.

12. Wolff L, Parkinson J, and White PD. Bundle branch block with short PR interval in healthy young people prone to paroxysmal tachycardia Am Heart J 1930, 5: 686-704.

13. Gollob MH. Glycogen storage disease as a unifying mechanism of disease in the PRKAG2 cardiac syndrome. Biochem Soc Transactions 2003, 31: 228-231.

14. Seidman JG and Seidman CE. The Genetic Basis for Cardiomyopathy: from Mutation Identification to Mechanistic Paradigms Cell 2001, 104: 557-567.

15. Bulkley BH and Hutchins GM. Pompe's disease presenting as hypertrophic myocardiopathy with Wolff- Parkinson-White syndrome Am Heart J 1978, 96: 246-252. Hutchins GM. Am Heart J 1978, 96: 246-252.

16. Amato AA. Acid maltase deficiency and related myopathies Neural Clin 2000, 18: 151-165.

17. Francesconi M and Auff E. Cardiac arrhythmias and the adult form of type II glycogenosis NEJM 1982, 306: 937-938.

18. Wessels A, Markman MWM, Vermeulen JLM, Anderson RH, Moorman AFM, and Lamers WH. The Development of the Atrioventricular Junction in the Human Heart Cir Res 1996, 78: 110-117.

19. Janse MJ, Anderson RH, van Capelle FJL, and Durrer D. A combined electrophysiological and anatomical study of the human fetal heart. Am Heart J 1976, 91: 556-562.

20. Arad M, Moskowitz IP, Patel VV, Ahmed F and Seidman JG. Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White glycogen storage cardiomyopathy. Circ 2003, 107(22): 2850-2856.

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