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Hypogonadotropic hypogonadism 18 with or without anosmia(HH18)

MedGen UID:
815305
Concept ID:
C3808975
Disease or Syndrome
Synonym: HH18
 
Gene (location): IL17RD (3p14.3)
 
Monarch Initiative: MONDO:0014103
OMIM®: 615267

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/615267

Clinical features

From HPO
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
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.
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.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
Abnormality of the dentition
MedGen UID:
78084
Concept ID:
C0262444
Finding
Any abnormality of the teeth.
Hypogonadism
MedGen UID:
5711
Concept ID:
C0020619
Disease or Syndrome
A decreased functionality of the gonad.
Absence of pubertal development
MedGen UID:
375841
Concept ID:
C1846228
Finding

Professional guidelines

PubMed

Tritos NA, Miller KK
JAMA 2023 Apr 25;329(16):1386-1398. doi: 10.1001/jama.2023.5444. PMID: 37097352
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

Alexander EC, Faruqi D, Farquhar R, Unadkat A, Ng Yin K, Hoskyns R, Varughese R, Howard SR
Eur J Endocrinol 2024 Jan 3;190(1):S1-S11. doi: 10.1093/ejendo/lvad166. PMID: 38128110Free PMC Article
Yan CH, Jang SS, Lin HC, Ma Y, Khanwalkar AR, Thai A, Patel ZM
Int Forum Allergy Rhinol 2023 Jun;13(6):989-997. Epub 2022 Dec 21 doi: 10.1002/alr.23116. PMID: 36507615Free 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
Bougakov D, Podell K, Goldberg E
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Drugs Aging 2019 Nov;36(11):981-989. doi: 10.1007/s40266-019-00716-2. PMID: 31595418Free PMC Article

Diagnosis

Mohanraj S, Prasad HK
Indian J Pediatr 2023 Jun;90(6):590-597. Epub 2023 May 2 doi: 10.1007/s12098-023-04577-x. PMID: 37127825
Schrag A, Bohlken J, Dammertz L, Teipel S, Hermann W, Akmatov MK, Bätzing J, Holstiege J
JAMA Neurol 2023 Feb 1;80(2):161-171. doi: 10.1001/jamaneurol.2022.3902. PMID: 36342675Free PMC Article
Dong Y, Li Y, Liu K, Han X, Liu R, Ren Y, Cong L, Zhang Q, Hou T, Song L, Tang S, Shi L, Luo Y, Kalpouzos G, Laukka EJ, Winblad B, Wang Y, Du Y, Qiu C
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Tartaglia N, Ayari N, Howell S, D'Epagnier C, Zeitler P
Acta Paediatr 2011 Jun;100(6):851-60. Epub 2011 Apr 8 doi: 10.1111/j.1651-2227.2011.02235.x. PMID: 21342258Free PMC Article

Therapy

Alexander EC, Faruqi D, Farquhar R, Unadkat A, Ng Yin K, Hoskyns R, Varughese R, Howard SR
Eur J Endocrinol 2024 Jan 3;190(1):S1-S11. doi: 10.1093/ejendo/lvad166. PMID: 38128110Free PMC Article
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Int Forum Allergy Rhinol 2023 Jun;13(6):989-997. Epub 2022 Dec 21 doi: 10.1002/alr.23116. PMID: 36507615Free PMC Article
Yabluchanskiy A, Tsitouras PD
Drugs Aging 2019 Nov;36(11):981-989. doi: 10.1007/s40266-019-00716-2. PMID: 31595418Free PMC Article
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Sports Med 2017 Sep;47(9):1869-1883. doi: 10.1007/s40279-017-0709-z. PMID: 28258581

Prognosis

Mohanraj S, Prasad HK
Indian J Pediatr 2023 Jun;90(6):590-597. Epub 2023 May 2 doi: 10.1007/s12098-023-04577-x. PMID: 37127825
Corona G, Vena W, Pizzocaro A, Vignozzi L, Sforza A, Maggi M
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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

Corona G, Vena W, Pizzocaro A, Vignozzi L, Sforza A, Maggi M
Andrology 2023 Feb;11(2):204-214. Epub 2022 Dec 29 doi: 10.1111/andr.13367. PMID: 36542412
Yan CH, Jang SS, Lin HC, Ma Y, Khanwalkar AR, Thai A, Patel ZM
Int Forum Allergy Rhinol 2023 Jun;13(6):989-997. Epub 2022 Dec 21 doi: 10.1002/alr.23116. PMID: 36507615Free PMC Article
Gitman L, Newman D, Burak B, Reilly BK, Mudd P
Int J Pediatr Otorhinolaryngol 2023 Jan;164:111403. Epub 2022 Nov 25 doi: 10.1016/j.ijporl.2022.111403. PMID: 36463663Free PMC Article
Papazian EJ, Pinto JM
Chem Senses 2021 Jan 1;46 doi: 10.1093/chemse/bjab045. PMID: 34673938
Rouadi PW, Idriss SA, Bousquet J
Curr Opin Allergy Clin Immunol 2021 Jun 1;21(3):229-244. doi: 10.1097/ACI.0000000000000735. PMID: 33560742

Recent systematic reviews

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Eur J Endocrinol 2024 Jan 3;190(1):S1-S11. doi: 10.1093/ejendo/lvad166. PMID: 38128110Free PMC Article
Vance DE, Del Bene VA, Kamath V, Frank JS, Billings R, Cho DY, Byun JY, Jacob A, Anderson JN, Visscher K, Triebel K, Martin KM, Li W, Puga F, Fazeli PL
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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
J Med Virol 2022 Jan;94(1):253-262. Epub 2021 Sep 7 doi: 10.1002/jmv.27309. PMID: 34463956Free 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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