A familial association of the Wolff-Parkinson-White (WPW) pattern with and without cardiomyopathy

      has been described previously.

  It is due to a mutation in the g2 subunit of the AMP activated protein kinase gene (
PRKAG2).

  Familial WPW syndrome has an autosomal dominant mode of inheritance.

  In addition to the WPW pattern, ECGs from these patients may show a high incidence of

      paroxysmal
atrial fibrillation and flutter, sinus bradycardia and high-grade sino-atrial or A-V block.

      Furthermore, some patients may also demonstrate
left anterior fascicular block, and pseudo bi-atrial

      enlargement
(bi-atrial hypertrophy on ECG contrasting with normal atrial diameter on echocardiography).

      Atrial fibrillation may increase the risk of sudden death in these patients.

  Animal studies showed that the PRKAG2 mutants had increased AMPK activity that resulted in a

     
glycogen storage disease.

     
Infiltration of the specialized conduction system was thought to explain the findings of sinus and AV

      conduction disorders
.

      According to this study, preexcitation was due to disruption by glycogen-ladened myocytes rather than

      a specifically defined muscle bundle that characterizes the spontaneous forms of WPW.

      ECG findings suggestive of preexcitation are sometimes found in patients with glycogen storage diseases

      (
Pompe disease, Danon disease).



ECG findings of Pseudo-WPW Syndrome

  Sternick et al. suggested that PRKAG2 mutations are responsible for a diverse phenotype and

      not only the familial form of the WPW syndrome.

  Familial occurrence of
right bundle branch block, sinus bradycardia, and short PR interval should raise

      suspicion of a
mutant PRKAG2 gene.

  A slurred QRS complex may mimick a delta wave (hence named as "pseudo").

  Not all patients show myocardial hypertrophy.




References: (including links to abstract and/or full-text articles)

  J Med Invest 2018;65(1.2):1-8.

  Heart Rhythm 2018;15(2):267-276.

  Am J Case Rep 2017;18:766-776.

  Am J Med Genet A 2015;167A(12):2975-2984.

  Europace 2007;9(8):597-600.

  J Cardiovasc Electrophysiol 2006;17(7):724-732..

  J Am Coll Cardiol 2005;45(6):922-930.

  Indian Pacing Electrophysiol J 2003;3(4):197-201.

  Circulation 2003;107(22):2850-2856.

  J Clin Invest 2002;109(3):357-362.

  N Engl J Med 2001;344(24):1823-1831.

  J Clin Invest 1995;96(3):1216-1220.