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Hypogonadotropic hypogonadism 10 with or without anosmia(HH10)

MedGen UID:
766757
Concept ID:
C3553843
Disease or Syndrome
Synonym: HH10
 
Gene (location): TAC3 (12q13.3)
 
Monarch Initiative: MONDO:0013912
OMIM®: 614839

Disease characteristics

Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is characterized by inappropriately low serum concentrations of the gonadotropins LH (luteinizing hormone) and FSH (follicle-stimulating hormone) in the presence of low circulating concentrations of sex steroids. IGD is associated with a normal sense of smell (normosmic IGD) in approximately 40% of affected individuals and an impaired sense of smell (Kallmann syndrome) in approximately 60%. IGD can first become apparent in infancy, adolescence, or adulthood. Infant boys with congenital IGD often have micropenis and cryptorchidism. Adolescents and adults with IGD have clinical evidence of hypogonadism and incomplete sexual maturation on physical examination. Adult males with IGD tend to have prepubertal testicular volume (i.e., <4 mL), absence of secondary sexual features (e.g., facial and axillary hair growth, deepening of the voice), decreased muscle mass, diminished libido, erectile dysfunction, and infertility. Adult females have little or no breast development and primary amenorrhea. Although skeletal maturation is delayed, the rate of linear growth is usually normal except for the absence of a distinct pubertal growth spurt. [from GeneReviews]
Authors:
Ravikumar Balasubramanian  |  William F Crowley   view full author information

Additional description

From OMIM
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 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).' For a discussion of genetic heterogeneity of hypogonadotropic hypogonadism with or without anosmia, see 147950.  http://www.omim.org/entry/614839

Clinical features

From HPO
Primary amenorrhea
MedGen UID:
115918
Concept ID:
C0232939
Disease or Syndrome
Abnormally late or absent menarche in a female with normal secondary sexual characteristics.
Anosmia
MedGen UID:
1950
Concept ID:
C0003126
Finding
An inability to perceive odors. This is a general term describing inability to smell arising in any part of the process of smelling from absorption of odorants into the nasal mucous overlying the olfactory epithelium, diffusion to the cilia, binding to olfactory receptor sites, generation of action potentials in olfactory neurons, and perception of a smell.
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Hypogonadotropic hypogonadism
MedGen UID:
82883
Concept ID:
C0271623
Disease or Syndrome
Hypogonadotropic hypogonadism is characterized by reduced function of the gonads (testes in males or ovaries in females) and results from the absence of the gonadal stimulating pituitary hormones

Professional guidelines

PubMed

Jankovic J, Tan EK
J Neurol Neurosurg Psychiatry 2020 Aug;91(8):795-808. Epub 2020 Jun 23 doi: 10.1136/jnnp-2019-322338. PMID: 32576618
Gravholt CH, Viuff MH, Brun S, Stochholm K, Andersen NH
Nat Rev Endocrinol 2019 Oct;15(10):601-614. Epub 2019 Jun 18 doi: 10.1038/s41574-019-0224-4. PMID: 31213699
Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamäki J, Raivio T, Pitteloud N
Endocr Rev 2019 Apr 1;40(2):669-710. doi: 10.1210/er.2018-00116. PMID: 30698671

Recent clinical studies

Etiology

Ahmad SJ, Feigen CM, Vazquez JP, Kobets AJ, Altschul DJ
J Integr Neurosci 2022 Apr 6;21(3):77. doi: 10.31083/j.jin2103077. PMID: 35633158
Elvan-Tuz A, Karadag-Oncel E, Kiran S, Kanik-Yuksek S, Gulhan B, Hacimustafaoglu M, Ozdem-Alatas S, Kuyucu N, Ozdemir H, Egil O, Elmas-Bozdemir S, Polat M, Bursal-Duramaz B, Cem E, Apaydin G, Teksam O; TURK-COVID-19-Anosmia Study Group
Pediatr Infect Dis J 2022 Jun 1;41(6):473-477. Epub 2022 May 6 doi: 10.1097/INF.0000000000003526. PMID: 35349499Free PMC Article
Burges Watson DL, Campbell M, Hopkins C, Smith B, Kelly C, Deary V
PLoS One 2021;16(9):e0256998. Epub 2021 Sep 24 doi: 10.1371/journal.pone.0256998. PMID: 34559820Free PMC Article
Corona G, Goulis DG, Huhtaniemi I, Zitzmann M, Toppari J, Forti G, Vanderschueren D, Wu FC
Andrology 2020 Sep;8(5):970-987. Epub 2020 Mar 20 doi: 10.1111/andr.12770. PMID: 32026626
Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC, Yialamas MA
J Clin Endocrinol Metab 2018 May 1;103(5):1715-1744. doi: 10.1210/jc.2018-00229. PMID: 29562364

Diagnosis

Bandeira L, Silva BC, Bilezikian JP
Arch Endocrinol Metab 2022 Nov 11;66(5):739-747. doi: 10.20945/2359-3997000000563. PMID: 36382763Free PMC Article
Koyama S, Kondo K, Ueha R, Kashiwadani H, Heinbockel T
Int J Mol Sci 2021 Aug 18;22(16) doi: 10.3390/ijms22168912. PMID: 34445619Free PMC Article
Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamäki J, Raivio T, Pitteloud N
Endocr Rev 2019 Apr 1;40(2):669-710. doi: 10.1210/er.2018-00116. PMID: 30698671
Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC, Yialamas MA
J Clin Endocrinol Metab 2018 May 1;103(5):1715-1744. doi: 10.1210/jc.2018-00229. PMID: 29562364
Fraietta R, Zylberstejn DS, Esteves SC
Clinics (Sao Paulo) 2013;68 Suppl 1(Suppl 1):81-8. doi: 10.6061/clinics/2013(sup01)09. PMID: 23503957Free PMC Article

Therapy

García-Arnés JA, García-Casares N
Rev Clin Esp (Barc) 2022 Dec;222(10):612-620. Epub 2022 Nov 15 doi: 10.1016/j.rceng.2022.09.003. PMID: 36400345
Koyama S, Kondo K, Ueha R, Kashiwadani H, Heinbockel T
Int J Mol Sci 2021 Aug 18;22(16) doi: 10.3390/ijms22168912. PMID: 34445619Free PMC Article
Corona G, Goulis DG, Huhtaniemi I, Zitzmann M, Toppari J, Forti G, Vanderschueren D, Wu FC
Andrology 2020 Sep;8(5):970-987. Epub 2020 Mar 20 doi: 10.1111/andr.12770. PMID: 32026626
Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamäki J, Raivio T, Pitteloud N
Endocr Rev 2019 Apr 1;40(2):669-710. doi: 10.1210/er.2018-00116. PMID: 30698671
Bhasin S, Brito JP, Cunningham GR, Hayes FJ, Hodis HN, Matsumoto AM, Snyder PJ, Swerdloff RS, Wu FC, Yialamas MA
J Clin Endocrinol Metab 2018 May 1;103(5):1715-1744. doi: 10.1210/jc.2018-00229. PMID: 29562364

Prognosis

Cecchetti G, Agosta F, Canu E, Basaia S, Barbieri A, Cardamone R, Bernasconi MP, Castelnovo V, Cividini C, Cursi M, Vabanesi M, Impellizzeri M, Lazzarin SM, Fanelli GF, Minicucci F, Giacalone G, Falini A, Falautano M, Rovere-Querini P, Roveri L, Filippi M
J Neurol 2022 Jul;269(7):3400-3412. Epub 2022 Mar 6 doi: 10.1007/s00415-022-11047-5. PMID: 35249144Free PMC Article
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Mendelson M, Nel J, Blumberg L, Madhi SA, Dryden M, Stevens W, Venter FWD
S Afr Med J 2020 Nov 23;111(1):10-12. doi: 10.7196/SAMJ.2020.v111i11.15433. PMID: 33403997
Krzastek SC, Sharma D, Abdullah N, Sultan M, Machen GL, Wenzel JL, Ells A, Chen X, Kavoussi M, Costabile RA, Smith RP, Kavoussi PK
J Urol 2019 Nov;202(5):1029-1035. Epub 2019 Oct 9 doi: 10.1097/JU.0000000000000396. PMID: 31216250
Boehm U, Bouloux PM, Dattani MT, de Roux N, Dodé C, Dunkel L, Dwyer AA, Giacobini P, Hardelin JP, Juul A, Maghnie M, Pitteloud N, Prevot V, Raivio T, Tena-Sempere M, Quinton R, Young J
Nat Rev Endocrinol 2015 Sep;11(9):547-64. Epub 2015 Jul 21 doi: 10.1038/nrendo.2015.112. PMID: 26194704

Clinical prediction guides

Bandeira L, Silva BC, Bilezikian JP
Arch Endocrinol Metab 2022 Nov 11;66(5):739-747. doi: 10.20945/2359-3997000000563. PMID: 36382763Free PMC Article
Cecchetti G, Agosta F, Canu E, Basaia S, Barbieri A, Cardamone R, Bernasconi MP, Castelnovo V, Cividini C, Cursi M, Vabanesi M, Impellizzeri M, Lazzarin SM, Fanelli GF, Minicucci F, Giacalone G, Falini A, Falautano M, Rovere-Querini P, Roveri L, Filippi M
J Neurol 2022 Jul;269(7):3400-3412. Epub 2022 Mar 6 doi: 10.1007/s00415-022-11047-5. PMID: 35249144Free PMC Article
Raheem OA, Chen T, Akula KP, Greenberg J, Le TV, Chernobylsky D, Sikka SC, Walsh TJ
Sex Med Rev 2021 Jul;9(3):381-392. Epub 2021 Apr 29 doi: 10.1016/j.sxmr.2020.08.003. PMID: 33933392
Topaloğlu AK
J Clin Res Pediatr Endocrinol 2017 Dec 30;9(Suppl 2):113-122. Epub 2017 Dec 27 doi: 10.4274/jcrpe.2017.S010. PMID: 29280744Free PMC Article
Boehm U, Bouloux PM, Dattani MT, de Roux N, Dodé C, Dunkel L, Dwyer AA, Giacobini P, Hardelin JP, Juul A, Maghnie M, Pitteloud N, Prevot V, Raivio T, Tena-Sempere M, Quinton R, Young J
Nat Rev Endocrinol 2015 Sep;11(9):547-64. Epub 2015 Jul 21 doi: 10.1038/nrendo.2015.112. PMID: 26194704

Recent systematic reviews

Lopez-Leon S, Wegman-Ostrosky T, Ayuzo Del Valle NC, Perelman C, Sepulveda R, Rebolledo PA, Cuapio A, Villapol S
Sci Rep 2022 Jun 23;12(1):9950. doi: 10.1038/s41598-022-13495-5. PMID: 35739136Free PMC Article
Huijben M, Lock MTWT, de Kemp VF, de Kort LMO, van Breda HMK
Andrology 2022 Mar;10(3):451-469. Epub 2022 Jan 8 doi: 10.1111/andr.13146. PMID: 34933414
Malik P, Patel K, Pinto C, Jaiswal R, Tirupathi R, Pillai S, Patel U
J Med Virol 2022 Jan;94(1):253-262. Epub 2021 Sep 7 doi: 10.1002/jmv.27309. PMID: 34463956Free PMC Article
Gómez-Ochoa SA, Franco OH, Rojas LZ, Raguindin PF, Roa-Díaz ZM, Wyssmann BM, Guevara SLR, Echeverría LE, Glisic M, Muka T
Am J Epidemiol 2021 Jan 4;190(1):161-175. doi: 10.1093/aje/kwaa191. PMID: 32870978Free PMC Article
Agyeman AA, Chin KL, Landersdorfer CB, Liew D, Ofori-Asenso R
Mayo Clin Proc 2020 Aug;95(8):1621-1631. Epub 2020 Jun 6 doi: 10.1016/j.mayocp.2020.05.030. PMID: 32753137Free PMC Article

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