Interestingly, the first mutations implicated in clonal expansion in spermatogonial stem cells were initially shown to cause developmental disorders such as Noonan and Costello syndrome (caused by PTPN11 and HRAS mutations, respectively) [78, 81, 82], Apert, Crouzon, and Pfeiffer syndromes (FGFR2) [81, 83], achondroplasia, Muenke syndrome and thanatophoric dysplasia (FGFR3) [81, 82], and multiple endocrine neoplasia (RET) [84]. This evidence concerns the gene HRAS and Costello syndrome.