👤 Fevronia Papagianni

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. 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. 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. 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. Show less

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS) that causes progressive neurological disability in most patients due to neurodegeneration. Activated immune cells infiltrate the CNS, triggering an inflammatory cascade that leads to demyelination and axonal injury. Non-inflammatory mechanisms are also involved in axonal degeneration, although they are not fully elucidated yet. Current therapies focus on immunosuppression; however, no therapies to promote regeneration, myelin repair, or maintenance are currently available. Two different negative regulators of myelination have been proposed as promising targets to induce remyelination and regeneration, namely the Nogo-A and LINGO-1 proteins. Although Nogo-A was first discovered as a potent neurite outgrowth inhibitor in the CNS, it has emerged as a multifunctional protein. It is involved in numerous developmental processes and is necessary for shaping and later maintaining CNS structure and functionality. However, the growth-restricting properties of Nogo-A have negative effects on CNS injury or disease. LINGO-1 is also an inhibitor of neurite outgrowth, axonal regeneration, oligodendrocyte differentiation, and myelin production. Inhibiting the actions of Nogo-A or LINGO-1 promotes remyelination both in vitro and in vivo, while Nogo-A or LINGO-1 antagonists have been suggested as promising therapeutic approaches for demyelinating diseases. In this review, we focus on these two negative regulators of myelination while also providing an overview of the available data on the effects of Nogo-A and LINGO-1 inhibition on oligodendrocyte differentiation and remyelination. Show less