Abstract
Idiopathic hypogonadotropic hypogonadism (IHH) is a group of rare developmental disorders characterized by low gonadotropin levels in the face of low sex steroid hormone concentrations. IHH is practically divided into two major groups according to the olfactory function: normal sense of smell (normosmia) nIHH, and reduced sense of smell (hyposmia/anosmia) Kallmann syndrome (KS). Although mutations in more than 50 genes have been associated with IHH so far, only half of those cases were explained by gene mutations. Various combinations of deleterious variants in different genes as causes of IHH have been increasingly recognized (Oligogenic etiology). In addition to the complexity of inheritance patterns, the spontaneous or sex steroid-induced clinical recovery from IHH, which is seen in approximately 10–20% of cases, blurs further the phenotype/genotype relationship in IHH, and poses challenging steps in new IHH gene discovery. Beyond helping for clinical diagnostics, identification of the genetic mutations in the pathophysiology of IHH is hoped to shed light on the central governance of the hypothalamo-pituitary-gonadal axis through life stages. This review aims to summarize the genetic etiology of IHH and discuss the clinical and physiological ramifications of the gene mutations.
Highlights
Idiopathic hypogonadotropic hypogonadism (IHH) refers to instances of hypogonadotropic hypogonadism (HH) that have no known etiology
IHH is divided into two categories with normal olfaction (normosmic idiopathic hypogonadotropic hypogonadism, and hyposmia or anosmia (Kallmann Syndrome (KS)) and can be congenital or acquired [1]
Recessive mutations in these genes have been reported in association with the 4H syndrome, which is characterized by hypomyelination, hypodontia, and hypogonadotropic hypogonadism [87,88]
Summary
Idiopathic hypogonadotropic hypogonadism (IHH) refers to instances of hypogonadotropic hypogonadism (HH) that have no known etiology. Researchers have recently associated more genes with IHH in complex pedigrees, often lacking proper genotype-phenotype segregations. This is probably due to a combination of oligogenic etiology [4] and clinical recovery [5], among other factors. AND “gene” OR “puberty” AND “mutation.” The search results were manually nearly 60 genes have been reported to be associated with IHH (Table 1). The increasing use of next-generation sequencing in for genetic-based studies (e.g., elucidating disease physiology, rapid diagnosis, or new clinical practice has been revolutionary for genetic-based studies (e.g., elucidating disease gene discoveries) [10].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
