Syndromic forms of congenital heart disease also can be caused by single genes or be of unknown genetic origin. In a larger case series with 44 patients with Ebstein anomaly, 12 (27 %) had syndromic presentation, and 7 of those had distinct disorders including CHARGE syndrome (N = 2), VACTERL association, Noonan syndrome, Kabuki syndrome, Holt-Oram syndrome, and Cornelia de Lange syndrome (one each) [12]. An additional two patients with CHARGE syndrome have been reported in the literature, both of which carry mutations in CHD7 (chromodomain helicase DNA binding protein 7), as well as one additional patient each with Kabuki syndrome, Holt-Oram syndrome, Noonan syndrome, Williams syndrome, and Ellis-van Creveld syndrome without mutation screening [62–67]. A single patient with thiamine-responsive megaloblastic anemia and Ebstein anomaly has been reported; interestingly, several other cardiac defects have been described in this syndrome, including one case of atrial standstill, which can be part of Ebstein syndrome [68–70]. A relatively high number of patients with Ebstein anomaly and Down syndrome have been reported in the literature (Table 53.1); however, one has to keep in mind that the denominator of all children born with trisomy 21 is much higher than for all other chromosomal imbalances listed here.