Intersex Disorders

Abstract

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 α‐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.

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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.

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.

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

anti‐Müllerian hormone (AMH); LocusID: 268. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=268

nuclear receptor subfamily 0, group B, member 1 (NR0B1); LocusID: 190. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=190

nuclear receptor subfamily 5, group A, member 1; (NR5A1); LocusID: 2516. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2516

SRY (sex determining region Y)‐box 9 (SOX9); LocusID: 6662. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6662

sex determining region Y (SRY); LocusID: 6736. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=6736

Wilms tumor 1 (WT1); LocusID: 7490. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=7490

anti‐Müllerian hormone (AMH); MIM number: 600957. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?600957

nuclear receptor subfamily 0, group B, member 1 (NR0B1); MIM number: 300200. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?300200

nuclear receptor subfamily 5, group A, member 1; (NR5A1); MIM number: 184757. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?184757

SRY (sex determining region Y)‐box 9 (SOX9); MIM number: 114290. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?114290

sex determining region Y (SRY); MIM number: 480000. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?480000

Wilms tumor 1 (WT1); MIM number: 194070. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?194070

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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]