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Hypogonadotropic hypogonadism 7 with or without anosmia(HH7)

MedGen UID:
Concept ID:
Disease or Syndrome
Synonyms: HH7; HYPOGONADOTROPIC HYPOGONADISM 7 WITHOUT ANOSMIA; Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency
SNOMED CT: Idiopathic hypogonadotropic hypogonadism (123953004); Idiopathic gonadotrophin deficiency (123953004)
Genes (locations): AXL (19q13.2); CCDC141 (2q31.2); DUSP6 (12q21.33); FEZF1 (7q31.32); FGF17 (8p21.3); GNRH1 (8p21.2); GNRHR (4q13.2); SEMA3E (7q21.11); SPRY4 (5q31.3); SRA1 (5q31.3); WDR11 (10q26.12)
Monarch Initiative: MONDO:0007794
OMIM®: 146110

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]
Ravikumar Balasubramanian  |  William F Crowley   view full author information

Additional description

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/146110

Clinical features

From HPO
MedGen UID:
Concept ID:
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).
MedGen UID:
Concept ID:
Inability to conceive for at least one year after trying and having unprotected sex. Causes of female infertility include endometriosis, fallopian tubes obstruction, and polycystic ovary syndrome. Causes of male infertility include abnormal sperm production or function, blockage of the epididymis, blockage of the ejaculatory ducts, hypospadias, exposure to pesticides, and health related issues.
Primary amenorrhea
MedGen UID:
Concept ID:
Disease or Syndrome
Abnormally late or absent menarche in a female with normal secondary sexual characteristics.
Decreased testicular size
MedGen UID:
Concept ID:
Reduced volume of the testicle (the male gonad).
MedGen UID:
Concept ID:
Congenital Abnormality
Abnormally small penis. At birth, the normal penis is about 3 cm (stretched length from pubic tubercle to tip of penis) with micropenis less than 2.0-2.5 cm.
Abnormality of the sense of smell
MedGen UID:
Concept ID:
An anomaly in the ability to perceive and distinguish scents (odors).
Sparse pubic hair
MedGen UID:
Concept ID:
Reduced number or density of pubic hair.
Sparse axillary hair
MedGen UID:
Concept ID:
Reduced number or density of axillary hair.
Hypogonadotropic hypogonadism
MedGen UID:
Concept ID:
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
MedGen UID:
Concept ID:
Disease or Syndrome
Abnormal development of large mammary glands in males resulting in breast enlargement.

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Barone B, Napolitano L, Abate M, Cirillo L, Reccia P, Passaro F, Turco C, Morra S, Mastrangelo F, Scarpato A, Amicuzi U, Morgera V, Romano L, Calace FP, Pandolfo SD, De Luca L, Aveta A, Sicignano E, Trivellato M, Spena G, D'Alterio C, Fusco GM, Vitale R, Arcaniolo D, Crocetto F
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