Congenital Hypogonadotropic Hypogonadism With Novel Pathogenic Variants in FGFR1 and GNRHR

Shinta Yamamoto; Hanako Nakajima; Hiroshi Okada; Naoko Nakanishi; Masahide Hamaguchi; Michiaki Fukui

doi:10.1210/jcemcr/luae254

Congenital Hypogonadotropic Hypogonadism With Novel Pathogenic Variants in FGFR1 and GNRHR

JCEM Case Rep. 2025 Jan 15;3(1):luae254. doi: 10.1210/jcemcr/luae254. eCollection 2025 Jan.

Authors

Shinta Yamamoto¹, Hanako Nakajima¹, Hiroshi Okada¹, Naoko Nakanishi¹, Masahide Hamaguchi¹, Michiaki Fukui¹

Affiliation

¹ Department of Endocrinology and Metabolism, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

Abstract

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 (FGFR1) and gonadotropin-releasing hormone receptor (GNRHR) 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.

Keywords: FGFR1; GNRHR; congenital hypogonadotropic hypogonadism; gene pathogenic variant.

Publication types

Case Reports