Familial WPW syndrome

Familial WPW syndrome

Familial WPW syndrome: WPW syndrome is characterized by short PR interval, delta wave due to ventricular pre-excitation and consequent arrhythmias. About three percent of WPW syndrome can have a familial occurrence [1]. These familial cases have an autosomal dominant mode of inheritance and the genes responsible were first identified by Gollob MH and associates [2] who mapped the gene responsible to 7q34-q36. The gene which encodes for a protein AMPK (AMP- activated protein kinase) was identified as the causal gene (PRKAG2). Specifically, it encodes for the gamma-2 subunit which is a non catalytic subunit of AMPK. These were missense mutations in which a single nucleotide is substituted by another one, inducing a change of a single amino acid in the sequence of the final protein which is produced by the action of the gene.

Initial cases of familial WPW syndrome also had cardiac hypertrophy. Cardiac conduction disorders are also associated and occur around the fourth decade of life. These conduction abnormalities involve both the AV nodal and the accessory pathway and interestingly, they may require a pacemaker in spite of having two pathways for AV conduction. Pathophysiology of PRKAG2 mutation causing familial WPW syndrome resembles that of Pompe’s disease in that glycogen like substance deposition may contribute to cardiac hypertrophy. Glycogen like substance deposition has also a causative role in the genesis of conduction system disease as glycogen is more abundant in the conduction system than in myocardial tissue and excessive glycogen is known to be toxic to the conduction system, causing loss of function. Some authors have proposed that glycogen deposition disrupts the annulus fibrosus which insulates the atria from the ventricles and is responsible for pre-excitation [3].

References

  1. H J Vidaillet Jr, J C Pressley, E Henke, F E Harrell Jr, L D German. Familial occurrence of accessory atrioventricular pathways (preexcitation syndrome). N Engl J Med. 1987 Jul 9;317(2):65-9.
  2. M H Gollob, M S Green, A S Tang, T Gollob, A Karibe, A S Ali Hassan, F Ahmad, R Lozado, G Shah, L Fananapazir, L L Bachinski, R Roberts. Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N Engl J Med. 2001 Jun 14;344(24):1823-31.
  3. Michael Arad, Ivan P Moskowitz, Vickas V Patel, Ferhaan Ahmad, Antonio R Perez-Atayde, Douglas B Sawyer, Mark Walter, Guo H Li, Patrick G Burgon, Colin T Maguire, David Stapleton, Joachim P Schmitt, X X Guo, Anne Pizard, Sabina Kupershmidt, Dan M Roden, Charles I Berul, Christine E Seidman, J G Seidman. Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White syndrome in glycogen storage cardiomyopathy. Circulation. 2003 Jun 10;107(22):2850-6.