title: Genetic basis and variable phenotypic expression of Kallmann syndrome: towards a unifying theory.
abstract: Idiopathic hypogonadotropic hypogonadism (IHH) is defined by absent or incomplete puberty and characterised biochemically by low levels of sex steroids, with low or inappropriately normal gonadotropin hormones. IHH is frequently accompanied by non-reproductive abnormalities, most commonly anosmia, which is present in 50-60% of cases and defines Kallmann syndrome. The understanding of IHH has undergone rapid evolution, both in respect of genetics and breadth of phenotype. Once considered in monogenic Mendelian terms, it is now more coherently understood as a complex genetic condition. Oligogenic and complex genetic-environmental interactions have now been identified, with physiological and environmental factors interacting in genetically susceptible individuals to alter the clinical course and phenotype. These potentially link IHH to ancient evolutionary pressures on the ancestral human genome.
authors.affiliation: Endocrine Research Group, Institute for Genetic Medicine, University of Newcastle-upon-Tyne, UK.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Mitchell
authors.forename: Andrew
authors.initials: A
authors.lastname: Dwyer
authors.forename: Nelly
authors.initials: N
authors.lastname: Pitteloud
authors.forename: Richard
authors.initials: R
authors.lastname: Quinton
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D017436:Kallmann Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D020412:Multifactorial Inheritance; D010641:Phenotype; D012727:Sex Characteristics; D015398:Signal Transduction