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Hypogonadotropic hypogonadism 20 with or without anosmia(HH20)

MedGen UID:
815313
Concept ID:
C3808983
Disease or Syndrome
Synonyms: HH20; HYPOGONADOTROPIC HYPOGONADISM 20 WITH ANOSMIA; HYPOGONADOTROPIC HYPOGONADISM 20 WITH ANOSMIA, SUSCEPTIBILITY TO
 
Gene (location): FGF17 (8p21.3)
 
Monarch Initiative: MONDO:0014106
OMIM®: 615270

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/615270

Clinical features

From HPO
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).
Hypogonadism
MedGen UID:
5711
Concept ID:
C0020619
Disease or Syndrome
A decreased functionality of the gonad.
Delayed puberty
MedGen UID:
46203
Concept ID:
C0034012
Pathologic Function
Passing the age when puberty normally occurs with no physical or hormonal signs of the onset of puberty.

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
Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamäki J, Raivio T, Pitteloud N
Endocr Rev 2019 Apr 1;40(2):669-710. doi: 10.1210/er.2018-00116. PMID: 30698671
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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Diagnosis

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Can J Neurol Sci 2021 Jan;48(1):9-24. Epub 2020 Aug 5 doi: 10.1017/cjn.2020.173. PMID: 32753076Free PMC Article
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Therapy

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Prognosis

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Clinical prediction guides

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Nat Rev Endocrinol 2015 Sep;11(9):547-64. Epub 2015 Jul 21 doi: 10.1038/nrendo.2015.112. PMID: 26194704

Recent systematic reviews

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