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Hypogonadotropic hypogonadism 14 with or without anosmia(HH14)

MedGen UID:
761703
Concept ID:
C3540450
Disease or Syndrome
Synonyms: HH14; HYPOGONADOTROPIC HYPOGONADISM 14 WITHOUT ANOSMIA
 
Gene (location): WDR11 (10q26.12)
 
Monarch Initiative: MONDO:0013926
OMIM®: 614858

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/614858

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Primary amenorrhea
MedGen UID:
115918
Concept ID:
C0232939
Disease or Syndrome
Abnormally late or absent menarche in a female with normal secondary sexual characteristics.
Decreased testicular size
MedGen UID:
66027
Concept ID:
C0241355
Finding
Reduced volume of the testicle (the male gonad).
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.
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
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Nat Rev Endocrinol 2018 Aug;14(8):476-500. doi: 10.1038/s41574-018-0042-0. PMID: 29959430Free PMC Article
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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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
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Dabaja A, Wosnitzer M, Goldstein M
Curr Urol Rep 2013 Aug;14(4):309-14. doi: 10.1007/s11934-013-0339-4. PMID: 23754533
Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, Chanoine JP, Rubenstein J, Mohammadi M, Tsai PS, Sidis Y, Lage K, Pitteloud N
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Diagnosis

Mohanraj S, Prasad HK
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Roy D, Ghosh R, Dubey S, Dubey MJ, Benito-León J, Kanti Ray B
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Therapy

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Luskin K, Thakrar H, White A
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Prognosis

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Expert Rev Endocrinol Metab 2019 Nov;14(6):369-380. Epub 2019 Oct 7 doi: 10.1080/17446651.2019.1671821. PMID: 31587581
Miraoui H, Dwyer AA, Sykiotis GP, Plummer L, Chung W, Feng B, Beenken A, Clarke J, Pers TH, Dworzynski P, Keefe K, Niedziela M, Raivio T, Crowley WF Jr, Seminara SB, Quinton R, Hughes VA, Kumanov P, Young J, Yialamas MA, Hall JE, Van Vliet G, Chanoine JP, Rubenstein J, Mohammadi M, Tsai PS, Sidis Y, Lage K, Pitteloud N
Am J Hum Genet 2013 May 2;92(5):725-43. doi: 10.1016/j.ajhg.2013.04.008. PMID: 23643382Free PMC Article

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
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
Morris GC, Lloyd-Evans E, Cahill DJ
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Butler G, Purushothaman P
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Recent systematic reviews

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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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