Gonadotropin-releasing hormone receptor mutation as a cause of pubertal delay

A mid-adolescent boy presented with pubertal delay and micropenis. His sister had amenorrhoea. Laboratory evaluation confirmed hypogonadotropic hypogonadism. Brain MRI showed normal pituitary and hypothalamus, though the olfactory bulbs assessment was limited by artefacts. Testosterone therapy enabled the development of secondary sexual characteristics. Subsequent genetic testing identified compound heterozygous pathogenic variants in the gonadotropin-releasing hormone receptor gene, establishing the molecular basis of isolated hypogonadotropic hypogonadism (IHH). Identifying a genetic cause allowed proper counselling regarding prognosis, fertility induction and familial risk. Management focuses on completing sexual maturation, fertility induction and genetic counselling. This case emphasises that mid-adolescents with absent sexual characteristics apart from pubic hair should be evaluated for hypogonadotropic hypogonadism. Early recognition and prompt investigation support timely pubertal induction, fertility preservation and genetic counselling, improving long-term outcomes. Furthermore, this report highlights the pivotal role of genetic testing in guiding the diagnosis and long-term treatment management in patients with IHH.