One possibility is that these patients lack cis-acting regulatory elements required for modulating TBX1 expression; alternatively, deletion of CRKL, another 22q11.2 gene that has also been linked to craniofacial and heart anomalies in mouse models (Guris et al., 2001, 2006; Motahari et al., 2019; Verhagen et al., 2012), triggers the craniofacial and cardiac defects of DiGeorge syndrome. Here, TBX1 is linked to 22q11.2 deletion syndrome.