A rare combination of hypogonadotropic hypogonadism, GH deficiency and rectal atresia in a female with an FGFR1 variant: a case report and systematic review of the literature.

PURPOSE

To report a case with combined pituitary hormone deficiency (CPHD) and Fibroblast growth factor receptor 1 (FGFR1) gene defect, and summarize the clinical characteristics of similar cases by reviewing the current reports from the literature.

METHODS

A 24-year-old woman was admitted to the outpatient endocrinology unit with a diagnosis of primary amenorrhea, history of Growth Hormone deficiency and multiple congenital anomalies including rectal atresia. The subsequent hormonal investigation led to the diagnosis of hypogonadotropic hypogonadism and persistent GH deficiency. Abdominal and pelvic ultrasounds were normal whereas the brain MRI revealed a hypoplastic sella turcica with a hypoplastic anterior pituitary lobe, an ectopic posterior pituitary lobe and a thin pituitary stalk. The genetic analysis revealed a novel pathogenic missense heterozygous variant (c.1958G > A, p.Agr635Gln) in exon 15 of FGFR1 gene. PubMed, Scopus, and Web of Science were searched for the identification of studies reporting cases of CPHD with FGFR1 gene defects.

RESULTS

Of the 648 records retrieved, 10 were included in this review. A comprehensive overview of the cases was summarized, and their clinical and genetic characteristics were presented.

CONCLUSION

Although FGFR1 variants have been associated with Kallmann syndrome and isolated hypogonadotropic hypogonadism and recently with CPHD, the patient's phenotype includes phenotypic alterations not previously described, to the best of our knowledge, within the spectrum of non-reproductive features of either of these entities. Isolated GH deficiency combined with other non-common abnormalities exerts a great possibility for subsequent CPHD manifestation.

© 2025. The Author(s).