U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

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

Patel ZM, Holbrook EH, Turner JH, Adappa ND, Albers MW, Altundag A, Appenzeller S, Costanzo RM, Croy I, Davis GE, Dehgani-Mobaraki P, Doty RL, Duffy VB, Goldstein BJ, Gudis DA, Haehner A, Higgins TS, Hopkins C, Huart C, Hummel T, Jitaroon K, Kern RC, Khanwalkar AR, Kobayashi M, Kondo K, Lane AP, Lechner M, Leopold DA, Levy JM, Marmura MJ, Mclelland L, Miwa T, Moberg PJ, Mueller CA, Nigwekar SU, O'Brien EK, Paunescu TG, Pellegrino R, Philpott C, Pinto JM, Reiter ER, Roalf DR, Rowan NR, Schlosser RJ, Schwob J, Seiden AM, Smith TL, Soler ZM, Sowerby L, Tan BK, Thamboo A, Wrobel B, Yan CH
Int Forum Allergy Rhinol 2022 Apr;12(4):327-680. doi: 10.1002/alr.22929. PMID: 35373533
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

Siderowf A, Concha-Marambio L, Lafontant DE, Farris CM, Ma Y, Urenia PA, Nguyen H, Alcalay RN, Chahine LM, Foroud T, Galasko D, Kieburtz K, Merchant K, Mollenhauer B, Poston KL, Seibyl J, Simuni T, Tanner CM, Weintraub D, Videnovic A, Choi SH, Kurth R, Caspell-Garcia C, Coffey CS, Frasier M, Oliveira LMA, Hutten SJ, Sherer T, Marek K, Soto C; Parkinson's Progression Markers Initiative
Lancet Neurol 2023 May;22(5):407-417. doi: 10.1016/S1474-4422(23)00109-6. PMID: 37059509Free 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
Mol Neurobiol 2021 Feb;58(2):564-575. Epub 2020 Sep 29 doi: 10.1007/s12035-020-02152-5. PMID: 32990925Free PMC Article
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

Diagnosis

Siderowf A, Concha-Marambio L, Lafontant DE, Farris CM, Ma Y, Urenia PA, Nguyen H, Alcalay RN, Chahine LM, Foroud T, Galasko D, Kieburtz K, Merchant K, Mollenhauer B, Poston KL, Seibyl J, Simuni T, Tanner CM, Weintraub D, Videnovic A, Choi SH, Kurth R, Caspell-Garcia C, Coffey CS, Frasier M, Oliveira LMA, Hutten SJ, Sherer T, Marek K, Soto C; Parkinson's Progression Markers Initiative
Lancet Neurol 2023 May;22(5):407-417. doi: 10.1016/S1474-4422(23)00109-6. PMID: 37059509Free PMC Article
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
Alzheimers Dement 2023 Feb;19(2):589-601. Epub 2022 Sep 15 doi: 10.1002/alz.12777. PMID: 36341691
Marin C, Hummel T, Liu Z, Mullol J
J Allergy Clin Immunol Pract 2022 Jun;10(6):1423-1432. Epub 2022 Mar 17 doi: 10.1016/j.jaip.2022.03.003. PMID: 35307579Free PMC Article
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

Therapy

Premraj L, Kannapadi NV, Briggs J, Seal SM, Battaglini D, Fanning J, Suen J, Robba C, Fraser J, Cho SM
J Neurol Sci 2022 Mar 15;434:120162. Epub 2022 Jan 29 doi: 10.1016/j.jns.2022.120162. PMID: 35121209Free 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
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
Kwah JH, Peters AT
Allergy Asthma Proc 2019 Nov 1;40(6):380-384. doi: 10.2500/aap.2019.40.4252. PMID: 31690375
Sedaghat AR
Am Fam Physician 2017 Oct 15;96(8):500-506. PMID: 29094889

Prognosis

Ladani AP, Loganathan M, Kolikonda MK, Lippmann S
South Med J 2021 Dec;114(12):751-759. doi: 10.14423/SMJ.0000000000001337. PMID: 34853850Free PMC Article
Hsieh JW, Daskalou D, Detroux V, Sipione R, Senn P, Hugentobler M, Landis BN
Laryngoscope 2020 Oct;130(10):2442-2447. Epub 2020 Aug 1 doi: 10.1002/lary.28918. PMID: 32738075
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
Gaines AD
Allergy Asthma Proc 2010 May-Jun;31(3):185-9. doi: 10.2500/aap.2010.31.3357. PMID: 20615320

Clinical prediction guides

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
Thorstensen WM, Oie MR, Dahlslett SB, Sue-Chu M, Steinsvag SK, Helvik AS
Rhinology 2022 Feb 1;60(1):47-55. doi: 10.4193/Rhin21.037. PMID: 34647543
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
Altundag A, Yıldırım D, Tekcan Sanli DE, Cayonu M, Kandemirli SG, Sanli AN, Arici Duz O, Saatci O
Otolaryngol Head Neck Surg 2021 Jun;164(6):1337-1344. Epub 2020 Oct 13 doi: 10.1177/0194599820965920. PMID: 33045908Free PMC Article
Hsieh JW, Daskalou D, Detroux V, Sipione R, Senn P, Hugentobler M, Landis BN
Laryngoscope 2020 Oct;130(10):2442-2447. Epub 2020 Aug 1 doi: 10.1002/lary.28918. PMID: 32738075

Recent systematic reviews

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
Neuropsychol Rev 2024 Mar;34(1):155-191. Epub 2023 Feb 2 doi: 10.1007/s11065-022-09573-0. PMID: 36725781Free PMC Article
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
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
Hwang K, Yeom SH, Hwang SH
J Craniofac Surg 2017 May;28(3):803-805. doi: 10.1097/SCS.0000000000003482. PMID: 28468171

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...