However, considering the significant variable expressivity and phenotypic heterogeneity of CS syndromes, recent studies demonstrate the advantage of next-generation sequencing (NGS) using gene panels with less-frequently mutated CS core genes, such as IL11RA, POR, MSX2, and CDC45. Furthermore, WES and WGS enable targeted in silico analysis of a custom-designed CS-related gene panel and performance of a broader exome/genome analysis in cases returning negative results. Here, MSX2 is linked to Cowden syndrome 1.