A nonsense variant in FGFR1: a rare cause of combined pituitary hormone deficiency

ObjectivesVariants in fibroblast growth factor receptor-1 (FGFR1) may either cause isolated hypogonadotropic hypogonadism (IHH) or Kallmann syndrome (KS). Although the relationship of genes classically involved in IHH with combined pituitary hormone deficiency (CPHD) is well established, variants in FGFR1 have been presented as a rare cause of this phenotype recently.Case presentationHerein, we report an adopted 16-year-old male presented with delayed puberty and micropenis. He had undergone surgery for bilateral undescended testes in childhood. He was normosmic, and the pituitary imaging was normal. However, hypogonadotropic hypogonadism and growth hormone deficiency were detected, associated with a heterozygous nonsense variant (c.1864 C>T, p.R622X) in FGFR1.ConclusionsFGFR1 variants are among the causes of IHH and KS, which are inherited in an autosomal dominant manner and can be associated with midline defects. It should also be kept in mind that CPHD may be associated with FGFR1 variants in a subject with normal olfactory function.