SPRY4 and hypogonadotropic hypogonadism: Clearly, the FGFR signaling pathway plays a central role in the pathogenesis of KS/nIHH as mutations in several interacting genes have been identified (including HS6OST1, SPRY4, IL17RD, DUSP6, FGF17, and FLRT3) (Tornberg et al. 2011; Miraoui et al. 2013).