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Hypogonadotropic hypogonadism 19 with or without anosmia(HH19)

MedGen UID:
815311
Concept ID:
C3808981
Disease or Syndrome
Synonyms: HH19; HYPOGONADOTROPIC HYPOGONADISM 19 WITH ANOSMIA; HYPOGONADOTROPIC HYPOGONADISM 19 WITH ANOSMIA, SUSCEPTIBILITY TO; HYPOGONADOTROPIC HYPOGONADISM 19 WITHOUT ANOSMIA
 
Gene (location): DUSP6 (12q21.33)
 
Monarch Initiative: MONDO:0014105
OMIM®: 615269

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/615269

Clinical features

From HPO
Hearing impairment
MedGen UID:
235586
Concept ID:
C1384666
Disease or Syndrome
A decreased magnitude of the sensory perception of sound.
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.
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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Rahman MA, Islam K, Rahman S, Alamin M
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S Afr Med J 2020 Nov 23;111(1):10-12. doi: 10.7196/SAMJ.2020.v111i11.15433. PMID: 33403997
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Diagnosis

Marin C, Hummel T, Liu Z, Mullol J
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Therapy

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Sedaghat AR
Am Fam Physician 2017 Oct 15;96(8):500-506. PMID: 29094889

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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S Afr Med J 2020 Nov 23;111(1):10-12. doi: 10.7196/SAMJ.2020.v111i11.15433. PMID: 33403997
Boesveldt S, Postma EM, Boak D, Welge-Luessen A, Schöpf V, Mainland JD, Martens J, Ngai J, Duffy VB
Chem Senses 2017 Sep 1;42(7):513-523. doi: 10.1093/chemse/bjx025. PMID: 28531300Free 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

Clinical prediction guides

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
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J Neurol 2022 Jul;269(7):3400-3412. Epub 2022 Mar 6 doi: 10.1007/s00415-022-11047-5. PMID: 35249144Free PMC Article
Mullol J, Bachert C, Amin N, Desrosiers M, Hellings PW, Han JK, Jankowski R, Vodicka J, Gevaert P, Daizadeh N, Khan AH, Kamat S, Patel N, Graham NMH, Ruddy M, Staudinger H, Mannent LP
J Allergy Clin Immunol Pract 2022 Apr;10(4):1086-1095.e5. Epub 2021 Oct 7 doi: 10.1016/j.jaip.2021.09.037. PMID: 34628065
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Virol J 2021 Nov 18;18(1):225. doi: 10.1186/s12985-021-01699-6. PMID: 34794467Free PMC Article
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J Korean Med Sci 2020 May 11;35(18):e174. doi: 10.3346/jkms.2020.35.e174. PMID: 32383370Free PMC Article

Recent systematic reviews

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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
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Am J Epidemiol 2021 Jan 4;190(1):161-175. doi: 10.1093/aje/kwaa191. PMID: 32870978Free PMC Article
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