PITX2 and stroke disorder: Although the function of the specific variants included in the developmental pathway (PITX2, NKX2-5, GATA 4, and TBX5) is only partially known,4 these genes may impact cardiac development in early life, with evidence that missense mutations in TBX5 can lead to profound atrial transcriptional alteration and AF.63 Investigation of more sophisticated and novel biomarkers (eg, bone morphogenetic protein 1064,65) may yield more insights into understanding how this pathway impacts AF and stroke risk.