GRHL3 mutations were reported in patients with VWS (Peyrard-Janvid et al., 2014) and human spina bifida (Lemay et al., 2017), and polymorphisms were associated with both NSCL ± P and NSCPO phenotypes (Leslie et al., 2016; Mangold et al., 2016; Wang Y. et al., 2016; Eshete et al., 2018). This evidence concerns the gene GRHL3 and van der Woude syndrome.