A Novel GnRH1 Gene Mutation in Four Omani Male Siblings, Presentation and Management

Male hypogonadotropic hypogonadism results from defects in the GnRH or gonadotropins, causing sex-organ malformation, reduced or absent male secondary sexual characteristics, and infertility. Genetic mutations at the level of the hypothalamus or pituitary can result in this condition. This paper describes the clinical features and management of four Omani male siblings with hypogonadotropic hypogonadism carrying a novel mutation in the GnRH1 gene. Case 1: 16 years old, had micro penis and bilateral undescended testes. Pubertal induction started at 12 ½ years with testosterone injections. Case 2: 7 years old, had micro penis and bilateral retractile testes. He received HCG injections, followed by testosterone injections. Case 3: 6 years old, had micro penis and bilateral small inguinal testes. He was given HCG injections, followed by testosterone and FSH injections. Case 4: 3 1/2 years old, had a normal penile stretched length with bilateral undescended testes. Only the right testes was seen on ultrasound. On laparoscopic exploration, both testes were detected intra-abdominally. A repeat ultrasound did not show the testes, on either side. He received HCG injections. Conclusion: GnRH1 gene c.85C>G (p. His 29 to ASP) is a novel mutation that can result in micro penis, undescended, or atrophic testes and infertility. Treatment with testosterone, HCG and FSH can be given depending on the clinical findings. Further follow-up is required to understand the course of this condition and the impact of early management on fertility in the future.