RT Book, Section A1 Balasubramanian, Ravikumar A1 Crowley, William F. A2 Murray, Michael F. A2 Babyatsky, Mark W. A2 Giovanni, Monica A. A2 Alkuraya, Fowzan S. A2 Stewart, Douglas R. SR Print(0) ID 1102701911 T1 Hypogonadotropic Hypogonadism T2 Clinical Genomics: Practical Applications in Adult Patient Care YR 2014 FD 2014 PB McGraw-Hill Education PP New York, NY SN 9780071622448 LK accessbiomedicalscience.mhmedical.com/content.aspx?aid=1102701911 RD 2024/03/29 AB Disease summary:Kallmann syndrome (KS; hypogonadotropic hypogonadism and anosmia) and normosmic idiopathic hypogonadotropic hypogonadism (nIHH) represent the two major clinical presentations of humans with isolated deficiency of gonadotropin-releasing hormone (GnRH).Both KS and nIHH are more common in males than females (~3:1) and affected patients present with either complete or partial absence of puberty.During development, GnRH neurons arise from the embryonic olfactory placode and migrate in utero into the mediobasal hypothalamus where they secrete GnRH in a pulsatile manner. Combined developmental failure of both olfactory and GnRH neuronal migration result in KS, while isolated neuroendocrine failure of anatomically normal GnRH neurons results in nIHH.Hereditary basis:70% of KS or nIHH cases are apparently sporadic while the remainder is familial. However, on more detailed family expansion, a familial pattern can become evident. The inheritance pattern is heterogeneous. X-linked recessive, autosomal dominant, autosomal recessive, and oligogenic modes of inheritance are all documented.Differential diagnosis:In adolescents presenting with delayed puberty, the main differential diagnosis is constitutional delay in puberty (CDP). Time is the major factor in distinguishing CDP and KS or nIHH as subjects with CDP eventually enter puberty spontaneously and achieve normal sexual maturation.Other anatomic (CNS or pituitary tumors, head trauma, CNS irradiation, etc) or functional (chronic systemic illness, eating disorders, malnutrition) causes of hypogonadotropic hypogonadism must be excluded.