Hypogonadotropic hypogonadism

Definition:

Hypogonadotropic hypogonadism (HH) or secondary hypogonadism is defined as a clinical syndrome that results from gonadal failure due to abnormal pituitary gonadotropin levels. HH may result from either absent or inadequate hypothalamic gonadotropin releasing hormone (GnRH) secretion or failure of pituitary gonadotropin secretion. HH can be congenital or acquired. Congenital HH is clinically and genetically heterogeneous. Clinically, the disorder is characterized by an absence of puberty and infertility. The genetic condition is classically divided in 2 groups based on the presence or absence of olfaction dysfunction. Around 50-60% of the affected individuals exhibit anosmia or hyposmia in association with idiopathic HH, defining Kallmann syndrome. Acquired HH can be caused by drugs, infiltrative or infectious pituitary lesions, hyperprolactinemia, encephalic trauma, pituitary/brain radiation, exhausting exercise, abusive alcohol or illicit drug intake, and systemic diseases such as hemochromatosis, sarcoidosis and histiocytosis X.

References:

[1]. A Kemal Topaloglu, et al. Inactivating KISS1 mutation and hypogonadotropic hypogonadism. N Engl J Med. 2012 Feb 16;366(7):629-35. [Content Brief]

[2]. A Kemal Topaloglu, et al. Inactivating NHLH2 variants cause idiopathic hypogonadotropic hypogonadism and obesity in humans. Hum Genet. 2022 Feb;141(2):295-304. [Content Brief]

[3]. A Kemal Topaloglu, et al. TAC3 and TACR3 mutations in familial hypogonadotropic hypogonadism reveal a key role for Neurokinin B in the central control of reproduction. Nat Genet. 2009 Mar;41(3):354-358. [Content Brief]

[4]. Andrea Messina, et al. Neuron-Derived Neurotrophic Factor Is Mutated in Congenital Hypogonadotropic Hypogonadism. Am J Hum Genet. 2020 Jan 2;106(1):58-70. [Content Brief]

[5]. C H Matthews, et al. Primary amenorrhoea and infertility due to a mutation in the beta-subunit of follicle-stimulating hormone. Nat Genet. 1993 Sep;5(1):83-6. [Content Brief]

[6]. Catherine Dodé, et al. Kallmann syndrome. Eur J Hum Genet. 2009 Feb;17(2):139-46. [Content Brief]

[7]. Catherine Dodé, et al. Kallmann syndrome: mutations in the genes encoding prokineticin-2 and prokineticin receptor-2. PLoS Genet. 2006 Oct 20;2(10):e175. [Content Brief]

[8]. Catherine Dodé, et al. Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome. Nat Genet. 2003 Apr;33(4):463-5. [Content Brief]

[9]. D Bick, et al. Brief report: intragenic deletion of the KALIG-1 gene in Kallmann's syndrome. N Engl J Med. 1992 Jun 25;326(26):1752-5. [Content Brief]

[10]. Erica E Davis, et al. TCF12 haploinsufficiency causes autosomal dominant Kallmann syndrome and reveals network-level interactions between causal loci. Hum Mol Genet. 2020 Aug 11;29(14):2435-2450. [Content Brief]

[11]. Hichem Miraoui, et al. Mutations in FGF17, IL17RD, DUSP6, SPRY4, and FLRT3 are identified in individuals with congenital hypogonadotropic hypogonadism. Am J Hum Genet. 2013 May 2;92(5):725-43. [Content Brief]

[12]. Hyung-Goo Kim, et al. Mutations in CHD7, encoding a chromatin-remodeling protein, cause idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet. 2008 Oct;83(4):511-9. [Content Brief]

[13]. Hyung-Goo Kim, et al. WDR11, a WD protein that interacts with transcription factor EMX1, is mutated in idiopathic hypogonadotropic hypogonadism and Kallmann syndrome. Am J Hum Genet. 2010 Oct 8;87(4):465-79. [Content Brief]

[14]. Ivo Jorge Arnhold, et al. Inactivating mutations of luteinizing hormone beta-subunit or luteinizing hormone receptor cause oligo-amenorrhea and infertility in women. Horm Res. 2009;71(2):75-82. [Content Brief]

[15]. J-P Hardelin, et al. The complex genetics of Kallmann syndrome: KAL1, FGFR1, FGF8, PROKR2, PROK2, et al. Sex Dev. 2008;2(4-5):181-93. [Content Brief]

[16]. Janne Tornberg, et al. Heparan sulfate 6-O-sulfotransferase 1, a gene involved in extracellular sugar modifications, is mutated in patients with idiopathic hypogonadotrophic hypogonadism. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11524-9. [Content Brief]

[17]. Jérôme Bouligand, et al. Isolated familial hypogonadotropic hypogonadism and a GNRH1 mutation. N Engl J Med. 2009 Jun 25;360(26):2742-8. [Content Brief]

[18]. John Falardeau, et al. Decreased FGF8 signaling causes deficiency of gonadotropin-releasing hormone in humans and mice. J Clin Invest. 2008 Aug;118(8):2822-31. [Content Brief]

[19]. Kiyonori Miura, et al. Characterization of the human nasal embryonic LHRH factor gene, NELF, and a mutation screening among 65 patients with idiopathic hypogonadotropic hypogonadism (IHH). J Hum Genet. 2004;49(5):265-8. [Content Brief]

[20]. L Damla Kotan, et al. Mutations in FEZF1 cause Kallmann syndrome. Am J Hum Genet. 2014 Sep 4;95(3):326-31. [Content Brief]

[21]. N Pitteloud, et al. The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor. J Clin Endocrinol Metab. 2001 Jun;86(6):2470-5. [Content Brief]

[22]. Naresh Kumar Hanchate, et al. SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome. PLoS Genet. 2012 Aug;8(8):e1002896. [Content Brief]

[23]. Stephanie B Seminara, et al. The GPR54 gene as a regulator of puberty. N Engl J Med. 2003 Oct 23;349(17):1614-27. [Content Brief]

[24]. Ulrich Boehm, et al. Expert consensus document: European Consensus Statement on congenital hypogonadotropic hypogonadism--pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2015 Sep;11(9):547-64. [Content Brief]

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