Intersex Disorders

Kyriakie Sarafoglou, New York Presbyterian Hospital, Weill Medical College of Cornell University, New York, USA

Published online: January 2006

DOI: 10.1038/npg.els.0005508

Human intersex conditions arise during the complex developmental processes of sexual determination and differentiation resulting in discordance between genetic sex, gonadal sex and sexual phenotype. In humans and other mammals, a regulatory cascade of sex-linked and autosomal genes determines sex. Contingent on the gene mutation, a remarkable range of possible phenotypes are seen, including sex-reversed females and sex-reversed males.

Keywords: intersex; sex-determining region Y; pseudohermaphroditism; congenital adrenal hyperplasia; dysgenesis

Figure 1. onadal sex differentiation. The genes listed have been identified in humans and mice as being involved in gonadal development.
Figure 2. Male sex determination. The diagram shows the development of the male reproductive system. AMH: anti-Müllerian hormone.
Figure 3. Hormonal and genetic causes of male pseudohermaphroditism. ATR-X: X-linked -thalassemia mental retardation; DSS: dosage-sensitive sex reversal; HSD: hydroxysteroid dehydrogenase; WAGR: Wilms tumor, aniridia, genital malformations and mental retardation.
Figure 4. Pathways of normal adrenal and gonadal steroidogenesis.
close
 References
    Belville C, Josso N and Picard JY (1999) Persistence of Müllerian derivatives in males. American Journal of Medical Genetics 89: 218–223.
    Cameron FJ and Sinclair AH (1997) Mutations in SRY and SOX9 testis-determining genes. Human Mutation 9: 388–395.
    Goodfellow PN and Camerino G (1999) DAX-1 and ‘antitestis’ gene. Cellular and Molecular Life Sciences 55: 857–863.
    book Lovell-Badge R, Canning C and Sekido R (2002) "Sex determining genes in mice: building pathways". In: Chadwick and Goode (eds.) The Genetics and Biology of sex Determination. New York: John Wiley.
    McElreavey K and Fellous M (1999) Sex determination and the Y chromosome. American Journal of Medical Genetics 89: 176–185.
    book New MI and Ghizzoni L (2001) "An update of congenital adrenal hyperplasia". In: Lifshitz F (ed.) Pediatric Endocrinology: A Clinical Guide, 4th edn. New York: Marcel Dekker.
    Ortenberg J, Ostrer H and Sarafoglou K (2002) SRY gene expression in the ovotestes of XX true hermaphrodites. Journal of Urology 167(4): 1828–1831.
    Parker KL and Schimmer BP (1997) Steroidogenic factor 1: a key determinant of endocrine development and function. Endocrine Reviews 18: 361–377.
    Sarafoglou K and Ostrer H (2000) Familial sex reversal: a review. Journal of Clinical Endocrinology and Metabolism 85: 483–493.
    Sinclair AH, Berta P, Palmer MS, et al. (1990). A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346: 240–244.
    Vilain E and McCabe ERB (1998) Mammalian sex determination: from gonads to brain. Molecular Genetics and Metabolism 65: 74–84.
 Web Links
    ePath anti-Müllerian hormone (AMH); LocusID: 268. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=268
    ePath nuclear receptor subfamily 0, group B, member 1 (NR0B1); LocusID: 190. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=190
    ePath nuclear receptor subfamily 5, group A, member 1; (NR5A1); LocusID: 2516. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2516
    ePath SRY (sex determining region Y)-box 9 (SOX9); LocusID: 6662. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6662
    ePath sex determining region Y (SRY); LocusID: 6736. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6736
    ePath Wilms tumor 1 (WT1); LocusID: 7490. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7490
    ePath anti-Müllerian hormone (AMH); MIM number: 600957. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600957
    ePath nuclear receptor subfamily 0, group B, member 1 (NR0B1); MIM number: 300200. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?300200
    ePath nuclear receptor subfamily 5, group A, member 1; (NR5A1); MIM number: 184757. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?184757
    ePath SRY (sex determining region Y)-box 9 (SOX9); MIM number: 114290. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?114290
    ePath sex determining region Y (SRY); MIM number: 480000. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?480000
    ePath Wilms tumor 1 (WT1); MIM number: 194070. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?194070

Related Sub-Topics:

Developmental Disorders | Determination of Cell Fate | Organogenesis | Growth and Development | Specific Genetic Disorders | Mutational Mechanisms of Genetic Disease | Quantitative Genetics
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Intersex Disorders
 
How to Cite close
Sarafoglou, Kyriakie(Jan 2006) Intersex Disorders. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005508]