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Hypogonadotropic hypogonadism 17 with or without anosmia(HH17)

MedGen UID:
815301
Concept ID:
C3808971
Disease or Syndrome
Synonyms: HH17; HYPOGONADOTROPIC HYPOGONADISM 17 WITH ANOSMIA; HYPOGONADOTROPIC HYPOGONADISM 17 WITH OR WITHOUT ANOSMIA, SUSCEPTIBILITY TO; HYPOGONADOTROPIC HYPOGONADISM 17 WITHOUT ANOSMIA
 
Gene (location): SPRY4 (5q31.3)
 
Monarch Initiative: MONDO:0014102
OMIM®: 615266

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 as well as a discussion of oligogenicity of this disorder, see 147950.  http://www.omim.org/entry/615266

Clinical features

From HPO
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
Hyposmia
MedGen UID:
473584
Concept ID:
C2364082
Finding
A decreased sensitivity to odorants (that is, a decreased ability to perceive odors).
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Osteopenia is a term to define bone density that is not normal but also not as low as osteoporosis. By definition from the World Health Organization osteopenia is defined by bone densitometry as a T score -1 to -2.5.
Abnormality of the dentition
MedGen UID:
78084
Concept ID:
C0262444
Finding
Any abnormality of the teeth.
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

Piotrowicz K, Gąsowski J, Michel JP, Veronese N
Aging Clin Exp Res 2021 Oct;33(10):2887-2898. Epub 2021 Jul 30 doi: 10.1007/s40520-021-01942-8. PMID: 34328636Free PMC Article
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
Stamou MI, Georgopoulos NA
Metabolism 2018 Sep;86:124-134. Epub 2017 Nov 3 doi: 10.1016/j.metabol.2017.10.012. PMID: 29108899Free PMC Article

Recent clinical studies

Etiology

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Schiavetti I, Carmisciano L, Ponzano M, Cordioli C, Cocco E, Marfia GA, Inglese M, Filippi M, Radaelli M, Bergamaschi R, Immovilli P, Capobianco M, De Rossi N, Brichetto G, Scandellari C, Cavalla P, Pesci I, Confalonieri P, Perini P, Trojano M, Lanzillo R, Tedeschi G, Comi G, Battaglia MA, Patti F, Salvetti M, Sormani MP; MuSC-19 Study Group
Eur J Neurol 2022 Dec;29(12):3728-3736. Epub 2022 Sep 23 doi: 10.1111/ene.15554. PMID: 36086905Free PMC Article
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
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, Torres LO, Maggi M
J Sex Med 2020 Mar;17(3):447-460. Epub 2020 Jan 9 doi: 10.1016/j.jsxm.2019.11.270. PMID: 31928918

Diagnosis

Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, Cunningham GR, Granger CB, Khera M, Thompson IM Jr, Wang Q, Wolski K, Davey D, Kalahasti V, Khan N, Miller MG, Snabes MC, Chan A, Dubcenco E, Li X, Yi T, Huang B, Pencina KM, Travison TG, Nissen SE; TRAVERSE Study Investigators
N Engl J Med 2023 Jul 13;389(2):107-117. Epub 2023 Jun 16 doi: 10.1056/NEJMoa2215025. PMID: 37326322
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Roy D, Ghosh R, Dubey S, Dubey MJ, Benito-León J, Kanti Ray B
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Butler G, Purushothaman P
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Corona G, Torres LO, Maggi M
J Sex Med 2020 Mar;17(3):447-460. Epub 2020 Jan 9 doi: 10.1016/j.jsxm.2019.11.270. PMID: 31928918

Therapy

Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, Cunningham GR, Granger CB, Khera M, Thompson IM Jr, Wang Q, Wolski K, Davey D, Kalahasti V, Khan N, Miller MG, Snabes MC, Chan A, Dubcenco E, Li X, Yi T, Huang B, Pencina KM, Travison TG, Nissen SE; TRAVERSE Study Investigators
N Engl J Med 2023 Jul 13;389(2):107-117. Epub 2023 Jun 16 doi: 10.1056/NEJMoa2215025. PMID: 37326322
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
Prodam F, Caputo M, Mele C, Marzullo P, Aimaretti G
Nat Rev Endocrinol 2021 Feb;17(2):114-129. Epub 2020 Nov 27 doi: 10.1038/s41574-020-00437-2. PMID: 33247226
Rahman MA, Islam K, Rahman S, Alamin M
Mol Neurobiol 2021 Mar;58(3):1017-1023. Epub 2020 Oct 19 doi: 10.1007/s12035-020-02177-w. PMID: 33078369Free PMC Article
Corona G, Torres LO, Maggi M
J Sex Med 2020 Mar;17(3):447-460. Epub 2020 Jan 9 doi: 10.1016/j.jsxm.2019.11.270. PMID: 31928918

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
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J Gastroenterol Hepatol 2022 Mar;37(3):489-498. Epub 2021 Nov 4 doi: 10.1111/jgh.15717. PMID: 34672022Free PMC Article
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
Butler G, Purushothaman P
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Fung C, Dinh PC, Fossa SD, Travis LB
J Natl Compr Canc Netw 2019 Dec;17(12):1557-1568. doi: 10.6004/jnccn.2019.7369. PMID: 31805527

Clinical prediction guides

Lincoff AM, Bhasin S, Flevaris P, Mitchell LM, Basaria S, Boden WE, Cunningham GR, Granger CB, Khera M, Thompson IM Jr, Wang Q, Wolski K, Davey D, Kalahasti V, Khan N, Miller MG, Snabes MC, Chan A, Dubcenco E, Li X, Yi T, Huang B, Pencina KM, Travison TG, Nissen SE; TRAVERSE Study Investigators
N Engl J Med 2023 Jul 13;389(2):107-117. Epub 2023 Jun 16 doi: 10.1056/NEJMoa2215025. PMID: 37326322
Wisnivesky JP, Govindarajulu U, Bagiella E, Goswami R, Kale M, Campbell KN, Meliambro K, Chen Z, Aberg JA, Lin JJ
J Gen Intern Med 2022 May;37(7):1748-1753. Epub 2022 Mar 9 doi: 10.1007/s11606-022-07465-w. PMID: 35266128Free 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
Butler G, Purushothaman P
Minerva Pediatr 2020 Dec;72(6):484-490. Epub 2020 Aug 4 doi: 10.23736/S0026-4946.20.05968-X. PMID: 32748610
Corona G, Torres LO, Maggi M
J Sex Med 2020 Mar;17(3):447-460. Epub 2020 Jan 9 doi: 10.1016/j.jsxm.2019.11.270. PMID: 31928918

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
Malik P, Patel K, Pinto C, Jaiswal R, Tirupathi R, Pillai S, Patel U
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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
Christou MA, Christou PA, Markozannes G, Tsatsoulis A, Mastorakos G, Tigas S
Sports Med 2017 Sep;47(9):1869-1883. doi: 10.1007/s40279-017-0709-z. PMID: 28258581

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