Not all cases of WPW syndrome may have a genetic basis. Till recently, only one gene has been implicated in WPW syndrome – PRKAG2 gene which encodes for the gamma-2 regulatory subunit of AMP-activated protein kinase. The enzyme functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. Mutations in the gene causes distortion of the atrioventricular annulus by glycogen-filled myocytes and causes ventricular pre-excitation.
BMP2 is another gene which has been linked with WPW syndrome recently [Lalani SR, Thakuria JV, Cox GF, et al. 20p12.3 microdeletion predisposes to Wolff-Parkinson-White syndrome with variable neurocognitive deficits. J Med Genet 2009;46:168 –75]. Bone morphogenetic protein is involved in the development of the atrioventricular canal. Microdeletion of 20p12.3 produces pre-excitation (Wolff-Parkinson-White syndrome) along with variable neurocognitive deficits.