It should be noted, however, that increased Tbx5 dosage (gain-of-function mutations) was also associated with Holt-Oram syndrome and paroxysmal AF (reviewed in [41, 42]). Myocd is regarded as the most likely candidate among the genes affecting LA size [43], which is a clinical marker for risk stratification of AF development [64]. This evidence concerns the gene TBX5 and Holt-Oram syndrome.