Kallmann syndrome 2

Common Name(s)

Kallmann syndrome 2

Congenital idiopathic hypogonadotropic hypogonadism (IHH) is a disorder characterized by absent or incomplete sexual maturation by the age of 18 years, in conjunction with low levels of circulating gonadotropins and testosterone and no other abnormalities of the hypothalamic-pituitary axis. Idiopathic hypogonadotropic hypogonadism can be caused by an isolated defect in gonadotropin-releasing hormone (GNRH; {152760}) release, action, or both. Other associated nonreproductive phenotypes, such as anosmia, cleft palate, and sensorineural hearing loss, occur with variable frequency. In the presence of anosmia, idiopathic hypogonadotropic hypogonadism has been called 'Kallmann syndrome (KS),' whereas in the presence of a normal sense of smell, it has been termed 'normosmic idiopathic hypogonadotropic hypogonadism (nIHH)' (summary by {31:Raivio et al., 2007}). Because families have been found to segregate both KS and nIHH, the disorder is here referred to as 'hypogonadotropic hypogonadism with or without anosmia (HH).' Although HH was initially considered to be a monogenic disorder, the presence of marked locus heterogeneity, incomplete penetrance within pedigrees, and variable expressivity of pathogenic alleles, together with evidence for mutations in multiple genes in some affected individuals, resulted in a conceptual shift from monogenicity to an oligogenic framework in which a limited number of genes contribute pathogenic alleles to the genetic network responsible for the neuroendocrine control of human reproduction ({40:Sykiotis et al., 2010}). Genetic Heterogeneity of Hypogonadotropic Hypogonadism with or without Anosmia Other forms of autosomal hypogonadotropic hypogonadism with or without anosmia include HH3 ({244200}), caused by mutation in the PROKR2 gene ({607123}); HH4 ({610628}), caused by mutation in the PROK2 gene ({607002}); HH5 ({612370}), caused by mutation in the CHD7 gene ({608892}); HH6 ({612702}), caused by mutation in the FGF8 gene ({600483}); HH7 ({146110}), caused by mutation in the GNRHR gene ({138850}); HH8 ({614837}), caused by mutation in the KISS1R gene ({604161}); HH9 ({614838}), caused by mutation in the NELF gene ({608137}); HH10 ({614839}), caused by mutation in the TAC3 gene ({162330}); HH11 ({614840}), caused by mutation in the TACR3 gene ({162332}); HH12 ({614841}), caused by mutation in the GNRH1 gene ({152760}); HH13 ({614842}), caused by mutation in the KISS1 gene ({603286}); HH14 ({614858}), caused by mutation in the WDR11 gene ({606417}); HH15 ({614880}), caused by mutation in the HS6ST1 gene ({604846}); HH16 ({614897}), caused by mutation in the SEMA3A gene ({603961}); HH17 ({615266}), caused by mutation in the SPRY4 gene ({607984}); HH18 ({615267}), caused by mutation in the IL17RD gene ({606807}); HH19 ({615269}), caused by mutation in the DUSP6 gene ({602748}); HH20 ({615270}), caused by mutation in the FGF17 gene ({603725}); HH21 ({615271}), caused by mutation in the FLRT3 gene ({604808}); and HH22 ({616030}), caused by mutation in the FEZF1 gene ({613301}). There is also an X-linked form of the disorder (HH1; {308700}), caused by mutation in the KAL1 gene ({300836}). There is evidence that mutation in 2 or more of these genes can work in combination (oligogenicity) to produce GnRH-deficient conditions (summary by {5:Chan, 2011}). {40:Sykiotis et al. (2010)}, for example, demonstrated that of patients with an identifiable coding sequence mutation in 1 of 8 genes responsible for isolated GnRH deficiency, 11% carried mutations in at least one other of these genes as well. To assess oligogenicity in hypogonadotropic hypogonadism, {25:Miraoui et al. (2013)} analyzed 350 HH probands of European descent for mutation in 17 HH-associated genes. Mutations were identified in 124 (35%) of the probands, and 24 (19%) of the mutation-positive probands carried at least 2 mutant alleles from different genes. {25:Miraoui et al. (2013)} noted that 23 of the 24 oligogenic cases involved at least 1 gene associated with the fibroblast growth factor (FGF) network (see {601513}). {10:Dode et al. (2006)} stated that loss-of-function mutations in the KAL1 ({300836}) and FGFR1 genes account for approximately 20% of all cases of Kallmann syndrome and that mutations in the PROKR2 and PROK2 genes account for an additional 10%. {16:Gurbuz et al. (2012)} reviewed all causative mutations detected in multiplex families with normosmic hypogonadotropic hypogonadism over a 7-year period in Turkey. Mutations that segregated with disease were identified in 17 (77.2%) of 22 families studied, including mutations of the GNRHR gene in 7 (31.8%) of the families, TACR3 in 6 (27.2%), KISSR in 2 (9%), TAC3 in 1 (4.5%), and KISS1 in 1 (4.5%). Inheritance was autosomal recessive in all 17 families.
 

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Scientific Literature

Articles from the PubMed Database

Research articles describe the outcome of a single study. They are the published results of original research.
The terms "Kallmann syndrome 2" returned 5 free, full-text research articles on human participants. First 3 results:

[Maestre de San Juan-Kallmann-de Morsier syndrome: 2 clinical cases].
 

Author(s): M Fontecha García de Yébenes, R Hoyos Gurrea, C Iglesias Fernández, M D Rodríguez Arnao, A Rodríguez Sánchez

Journal: An Pediatr (Barc). 2009 Jul;71(1):88-9.

 

Last Updated: 29 Jun 2009

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Genetic analysis in patients with Kallmann syndrome: coexistence of mutations in prokineticin receptor 2 and KAL1.
 

Author(s): P Canto, P Munguía, D Söderlund, J J Castro, J P Méndez

Journal: J. Androl.. ;30(1):41-5.

 

Kallmann syndrome (KS) is characterized by the association of hypogonadotropic hypogonadism and anosmia or hyposmia. To date, 4 different genes have been identified as responsible for the presence of KS; however, in many cases no mutations have been found in any of these genes. Herein, ...

Last Updated: 3 Dec 2008

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Biallelic mutations in the prokineticin-2 gene in two sporadic cases of Kallmann syndrome.
 

Author(s): Chrystel Leroy, Corinne Fouveaut, Sandrine Leclercq, Sébastien Jacquemont, Hélène Du Boullay, James Lespinasse, Marc Delpech, Jean-Michel Dupont, Jean-Pierre Hardelin, Catherine Dodé

Journal: Eur. J. Hum. Genet.. 2008 Jul;16(7):865-8.

 

Kallmann syndrome is a developmental disease that combines hypogonadotropic hypogonadism and anosmia. Putative loss-of-function mutations in PROKR2 or PROK2, encoding prokineticin receptor-2 (a G protein-coupled receptor), and one of its ligands, prokineticin-2, respectively, have ...

Last Updated: 19 Jun 2008

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Reviews from the PubMed Database

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The terms "Kallmann syndrome 2" returned 0 free, full-text review articles on human participants.

 
 
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