Синдром Каллмана 2 типу, асоційований з рідкісною міссенс-мутацією гена FGFR1: клінічний випадок

Kallmann syndrome (KS) is a rare congenital form of isolated hypogonadotropic hypogonadism (IHH) associated with anosmia or hyposmia due to impaired migration of GnRH and olfactory neurons during embryogenesis. Objective — to describe the diagnostic work-up and clinical course of a rare case of KS type 2 associated with a mutation in the FGFR1 gene and to substantiate the initial hormone replacement therapy strategy to optimize early detection and management algorithms in pediatric endocrinology practice. Materials and methods. A systematic analysis of 23 contemporary peer-reviewed sources (PubMed/MEDLINE, Scopus, Web of Science) was performed with emphasis on clinical manifestations, genotype—phenotype correlations and differential diagnosis. The clinical case of a 17-year-old Ukrainian boy was reported in accordance with CARE guidelines and with informed parental consent. Comprehensive evaluation included medical history, physical examination, hormonal profiling, bone-age radiography, brain MRI with contrast, olfactometry, scrotal ultrasound, karyotyping and targeted next-generation sequencing (targeted next-generation sequencing (tNGS) panel for hypogonadotropic hypogonadism/Disorders of Sex Development) of 93 genes performed in a certified laboratory (Labcorp/Invitae, USA). Results and discussion. Molecular genetic analysis identified a rare heterozygous missense variant rs1064793123 in the FGFR1 gene (c.1019C>T). This study presents the first comprehensive clinical characterization of this variant with new phenotypic manifestations, additional evidence of pathogenicity, and practical algorithms for pediatric endocrinology in Ukraine. Conclusions. The case emphasizes the need for mandatory assessment of olfactory function in all adolescents with delayed puberty and early initiation of replacement therapy to prevent psychosocial and somatic complications.