SAT-012 Congenital Hypogonadotropic Hypogonadism Caused bya FrameshiftMutation inFGFR1masking as constitutional delay of puberty

Abstract Disclosure: E.M. Mohamed: None. I. Boughazi: None. A. Theodoraki: None. Z. Htut: None. Background: Congenital hypogonadotropic hypogonadism (CHH) is a rare condition characterized by impaired gonadotropin secretion, leading to absent or incomplete puberty and primary amenorrhoea in women. Mutations in the FGFR1 gene, which encodes fibroblast growth factor receptor 1, are known to cause CHH, often presenting with variable phenotypic features. Delayed diagnosis and treatment initiation can negatively impact psychosocial well-being and reproductive health. Case Presentation: A 30-year-old woman was initially evaluated at the age of 16 for incomplete puberty and primary amenorrhoea. Initial investigations revealed a 46XX karyotype, gonadotropins within the follicular phase reference range (LH 4.6 IU/L, FSH 5.9 IU/L), low serum oestradiol (68 pmol/L), absence of other causes of hypogonadism, and delayed bone age (12.6 years vs. chronological age of 16). Based on these findings, a provisional diagnosis of constitutional delay of puberty was made, and a low dose combined oral contraceptive pill (COCP) was prescribed. She took COCP intermittently for three years before seeking further evaluation for fertility concerns. Subsequent reassessment revealed gonadotropins at the lower end of the reference range (LH 3.4 IU/L [follicular phase: 2-10 IU/L], FSH 3.4 IU/L [follicular phase: 4-13 IU/L]), persistently low oestradiol (<92 pmol/L), anti-Müllerian hormone levels of 20 and 34 pmol/L, a small pituitary gland on MRI, and a small uterus. A diagnosis of CHH was established two years ago, and genetic testing identified a heterozygous pathogenic FGFR1 frameshift variant. Hormone replacement therapy (HRT) was initiated, and a bone density scan demonstrated values within the expected range for age (hip Z-score: 0.2, lumbar spine Z-score: -0.2). The patient has been referred for genetic counselling. Conclusion: This case highlights the diagnostic complexity of CHH and the importance of thorough evaluation, including genetic testing and periodic reassessment. Transitioning young adults to adult clinics at age of 18 often disrupts continuity of care, particularly when relocation for education occurs. Early identification of FGFR1 mutations enables a better understanding of disease aetiology and supports informed reproductive planning. Presentation: Saturday, July 12, 2025