Congenital Hypogonadotropic Hypogonadism With Novel Pathogenic Variants in FGFR1 and GNRHR

Congenital hypogonadotropic hypogonadism (CHH) can cause delayed secondary sexual characteristics and contribute to juvenile osteoporosis, with multiple causative genes having been reported. We treated a 27-year-old man diagnosed with central hypogonadism, presenting with delayed secondary sexual characteristics and juvenile osteoporosis, using bone resorption inhibitors and testosterone therapy. Genetic testing revealed missense variants both in the fibroblast growth factor receptor 1 (<i>FGFR1</i>) and gonadotropin-releasing hormone receptor (<i>GNRHR</i>) genes, a combination that has not been previously reported. This case represents a CHH caused by a novel combination of gene variants not registered in the human genome mutation database.