Combined pituitary hormone deficiency in a patient with an missense variant: case report and literature review.

Recent studies have indicated that heterozygous loss-of-function variants in fibroblast growth factor receptor 1 () are involved in the development of congenital hypogonadotropic hypogonadism and combined pituitary hormone deficiency (CPHD). We encountered a Japanese boy with short stature and pubertal failure. Endocrine studies showed GH, TSH, and LH/FSH deficiencies, and brain magnetic resonance imaging delineated hypoplastic anterior pituitary and ectopic posterior pituitary. The patient was treated with GH, -thyroxine, and hCG/rFSH. Next-generation sequencing panel for pituitary dysfunction identified a probably weak disease-associated heterozygous missense variant in (NM_023110.3:c.176A>T:p.(Asp59Val)), together with a probably non-deleterious heterozygous missense variant in (NM_032551.5:c.769G>C:p.(Val257Leu)). We also review six previously reported CHPD patients with probably deleterious variants. The data, in conjunction with the previously reported cases, argue for the relevance of variants to the development of CPHD.