The TP63 gene is essential for epithelial proliferation, differentiation, and maintenance during embryogenesis. Despite considerable clinical variability, TP63-related symptoms are characterized by ectodermal dysplasia, distal limb malformations, and orofacial clefts. We identified a novel TP63 variant (c.619A > G, p.K207E) in a seven-month-old Chinese patient with orofacial clefts and ectrodactyly but no evident signs of ectodermal dysplasia. This phenotype was rarely reported before. We summarized the presence of the three main TP63-related manifestations in the literature and noted different distributions of CP- and CL/P-related variants regarding p63 structural domains.

The TP63 gene has been described in 5 overlapping limb malformation disorders, including a rare autosomal dominant ectodermal disorder named acro-dermato-ungual-lacrimal-tooth (ADULT) syndrome. This article describes 2 patients with ectrodactyly and variable features related to ectodermal dysplasia/ADULT syndrome, and the polymorphism rs16864880 in the TP63 gene, which was not present in their parents. The role of this variant in the genesis of this condition is discussed, based upon a review of 40 cases. The results suggested that rs16864880 may not be directly related to ADULT syndrome. However, it is not possible to exclude its participation in gene interactions in the limb development pathway.