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Added "Genetic Profile" Heading and information on SRY positive XX males.
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Added information on SRY-negative XX males and the genes that may be involved.
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=== SRY-Positive ===
=== SRY-Positive ===
The [[SRY gene]] plays an important role in sex determination by initiating testicular development. In most XX males the SRY gene is present. The tip of the Y chromosome contains the SRY gene and, during [[Homologous recombination|recombination]], a translocation occurs in which the SRY gene on the Y chromosome is moved to become part of an X chromosome.<ref name=":32">{{Cite journal|last=Chen|first=Harold|date=2012|title=XX Male|url=|journal=Atlas of Genetic Diagnosis and Counseling|volume=|pages=2191-2196|doi=10.1007/978-1-4614-1037-9_250|via=}}</ref><ref>{{Cite journal|last=Margarit|first=Ester|last2=Coll|first2=M. Dolors|last3=Oliva|first3=Rafael|last4=Gómez|first4=David|last5=Soler|first5=Anna|last6=Ballesta|first6=Francisca|date=2000-01-03|title=SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite|url=http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1096-8628(20000103)90:13.0.CO;2-5/abstract|journal=American Journal of Medical Genetics|language=en|volume=90|issue=1|pages=25–28|doi=10.1002/(SICI)1096-8628(20000103)90:13.0.CO;2-5|issn=1096-8628}}</ref> The presence of the [[Translocation (genetics)|translocated]] SRY gene leads to an XX embryo developing male characteristics.  
The [[SRY gene]] plays an important role in sex determination by initiating testicular development. In most XX males the SRY gene is present. The tip of the Y chromosome contains the SRY gene and, during [[Homologous recombination|recombination]], a translocation occurs in which the SRY gene on the Y chromosome is moved to become part of an X chromosome.<ref name=":32">{{Cite journal|last=Chen|first=Harold|date=2012|title=XX Male|url=|journal=Atlas of Genetic Diagnosis and Counseling|volume=|pages=2191-2196|doi=10.1007/978-1-4614-1037-9_250|via=}}</ref><ref>{{Cite journal|last=Margarit|first=Ester|last2=Coll|first2=M. Dolors|last3=Oliva|first3=Rafael|last4=Gómez|first4=David|last5=Soler|first5=Anna|last6=Ballesta|first6=Francisca|date=2000-01-03|title=SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite|url=http://onlinelibrary.wiley.com/doi/10.1002/(SICI)1096-8628(20000103)90:13.0.CO;2-5/abstract|journal=American Journal of Medical Genetics|language=en|volume=90|issue=1|pages=25–28|doi=10.1002/(SICI)1096-8628(20000103)90:13.0.CO;2-5|issn=1096-8628}}</ref> The presence of the [[Translocation (genetics)|translocated]] SRY gene leads to an XX embryo developing male characteristics.  

=== SRY-Negative ===
In rare cases, an XX male does not have the SRY gene. The exact cause of this condition is unknown but it has been proposed that mutations in the [[SOX9]] gene may contribute to this syndrome since SOX9 plays a role in testes differentiation during development.<ref>{{Cite journal|last=Vetro|first=Annalisa|last2=Ciccone|first2=Roberto|last3=Giorda|first3=Roberto|last4=Patricelli|first4=Maria Grazia|last5=Mina|first5=Erika Della|last6=Forlino|first6=Antonella|last7=Zuffardi|first7=Orsetta|date=2011-01-01|title=XX males SRY negative: a confirmed cause of infertility|url=http://jmg.bmj.com/content/early/2011/06/07/jmedgenet-2011-100036|journal=Journal of Medical Genetics|language=en|pages=jmedgenet–2011–100036|doi=10.1136/jmedgenet-2011-100036|issn=0022-2593|pmid=21653197}}</ref><ref name=":7">{{Cite journal|last=Rajender|first=S.|date=2006-05-01|title=SRY-negative 46,XX male with normal genitals, complete masculinization and infertility|url=https://academic.oup.com/molehr/article/12/5/341/1005702|journal=Molecular Human Reproduction|language=en|volume=12|issue=5|pages=341–346|doi=10.1093/molehr/gal030|issn=1360-9947}}</ref> Another proposed cause is mutations to the [[DAX1]] gene which encodes a nuclear hormone receptor.<ref>{{Cite journal|last=Swain|first=Amanda|last2=Narvaez|first2=Veronica|last3=Burgoyne|first3=Paul|last4=Camerino|first4=Giovanna|last5=Lovell-Badge|first5=Robin|date=1998-02-19|title=Dax1 antagonizes Sry action in mammalian sex determination|url=https://www.nature.com/articles/35799|journal=Nature|language=en|volume=391|issue=6669|pages=761–767|doi=10.1038/35799|issn=1476-4687}}</ref><ref name=":4">{{Cite journal|last=Domenice|first=S.|last2=Corrêa|first2=R. V.|last3=Costa|first3=E. M. F.|last4=Nishi|first4=M. Y.|last5=Vilain|first5=E.|last6=Arnhold|first6=I. J. P.|last7=Mendonca|first7=B. B.|date=January 2004|title=Mutations in the SRY, DAX1, SF1 and WNT4 genes in Brazilian sex-reversed patients|url=http://www.scielo.br/scielo.php?script=sci_abstract&pid=S0100-879X2004000100020&lng=en&nrm=iso&tlng=en|journal=Brazilian Journal of Medical and Biological Research|volume=37|issue=1|pages=145–150|doi=10.1590/S0100-879X2004000100020|issn=0100-879X}}</ref> DAX1 represses masculinizing genes, therefore, if there is a [[Null allele|loss of function]] of DAX1 then testes can develop in an XX individual.<ref name=":4" /> Mutations in [[SF1 (gene)|SF1]] and [[WNT4]] genes are also being studied in connection with SRY-negative XX male syndrome.<ref name=":4" />


==Clinical diagnosis==
==Clinical diagnosis==

Revision as of 03:10, 29 November 2017

XX male syndrome
SpecialtyMedical genetics Edit this on Wikidata

XX male syndrome (also called de la Chapelle syndrome, for Albert de la Chapelle, who characterized it in 1972[1][2]) is a rare congenital condition where an individual with a female genotype has phenotypically male characteristics that can vary between cases.[3] In 90% of these individuals the syndrome is caused by unequal crossing over between X and Y chromosomes during meiosis in the father, which results in the X chromosome containing the normally male SRY gene.[3] When this X combines with a normal X from the mother during fertilization, the result is an XX male. Less common are SRY-negative XX males which can be caused by a mutation in an autosomal or X chromosomal gene or undetected mosaicism with a Y-bearing cell line.[3]

This syndrome is diagnosed through various detection methods and occurs in approximately 1:20 000 newborn males, making it less common than Klinefelter syndrome.[4][5]

Schematic of sexual differentiation in humans.

Presentation

The appearance of XX males can fall into one of three categories: 1) males that have normal internal and external genitalia, 2) males with external ambiguities, and 3) males that have both internal and external genital ambiguities (true hermaphrodites).[6] Genital ambiguities can include hypospadias, micropenis, and clitormegaly.[6] On average, the appearance of XX males differs from that of an XY male in that they are smaller in height and weight.[7] Most XX males have small testes, are sterile, and have an increase in maldescended testicles compared to XY males.[7][8] Some XX male individuals have decreased amounts of body hair and decreased libido.[9] Individuals with this condition sometimes have feminine characteristics, with varying degrees of gynecomastia but with no intra-abdominal Müllerian tissue.[9] According to research at the University of Oklahoma health science centers, despite XX males exhibiting feminine characteristics, their behaviours are usually representative of masculinity in their culture.[10] 

Genetic Profile

Males typically have one X chromosome and one Y chromosome in each diploid cell of their bodies. Females typically have two X chromosomes. XX males that are SRY-positive have two X chromosomes, with one of them containing genetic material from the Y chromosome, making them phenotypically male but genetically female.[11]

SRY-Positive

The SRY gene plays an important role in sex determination by initiating testicular development. In most XX males the SRY gene is present. The tip of the Y chromosome contains the SRY gene and, during recombination, a translocation occurs in which the SRY gene on the Y chromosome is moved to become part of an X chromosome.[12][13] The presence of the translocated SRY gene leads to an XX embryo developing male characteristics.  

SRY-Negative

In rare cases, an XX male does not have the SRY gene. The exact cause of this condition is unknown but it has been proposed that mutations in the SOX9 gene may contribute to this syndrome since SOX9 plays a role in testes differentiation during development.[14][15] Another proposed cause is mutations to the DAX1 gene which encodes a nuclear hormone receptor.[16][17] DAX1 represses masculinizing genes, therefore, if there is a loss of function of DAX1 then testes can develop in an XX individual.[17] Mutations in SF1 and WNT4 genes are also being studied in connection with SRY-negative XX male syndrome.[17]

Clinical diagnosis

  • Standard XX karyotype in two tissues (with at least one, or both, containing the male SRY gene)
  • Male external genitalia, sometimes showing hypospadias
  • Two testes which may or may not have descended the inguinal canal. Most XX males have descended testes.
  • Absence of Müllerian tissue

Treatment

See also

References

  1. ^ de la Chapelle, A (January 1972). "Analytic review: nature and origin of males with XX sex chromosomes". American Journal of Human Genetics. 24 (1): 71–105. ISSN 0002-9297. PMC 1762158. PMID 4622299.{{cite journal}}: CS1 maint: PMC format (link)
  2. ^ de la Chapelle, Albert (1985). Cytogenetics of the mammalian X-chromosome, Part B: Progress and topics in cytogenetics. New York: Alan Liss. pp. 75–85.
  3. ^ a b c Vorona, Elena; Zitzmann, Michael; Gromoll, Jörg; Schüring, Andreas N.; Nieschlag, Eberhard (2007-09-01). "Clinical, Endocrinological, and Epigenetic Features of the 46,XX Male Syndrome, Compared with 47,XXY Klinefelter Patients". The Journal of Clinical Endocrinology & Metabolism. 92 (9): 3458–3465. doi:10.1210/jc.2007-0447. ISSN 0021-972X.
  4. ^ Anık, Ahmet; Çatlı, Gönül; Abacı, Ayhan; Böber, Ece (2013-12). "46,XX Male Disorder of Sexual Development: A Case Report". Journal of Clinical Research in Pediatric Endocrinology. 5 (4): 258–260. doi:10.4274/Jcrpe.1098. ISSN 1308-5727. PMC 3890225. PMID 24379036. {{cite journal}}: Check date values in: |date= (help)CS1 maint: PMC format (link)
  5. ^ Ucan, Bekir; Ozbek, Mustafa; Topaloglu, Oya; Yesilurt, Ahmet; Gungunes, Askin; Demrici, Taner; Delibasi, Tunfay (July 2012). "46,XX Male Syndrome". Turkish Journal of Endocrinology and Metabolism. 17: 46–48. doi:10.4274/Tjem.2064.
  6. ^ a b Chen, Harold (2012). "XX Male". Atlas of Genetic Diagnosis and Counseling: 2191–2196. doi:10.1007/978-1-4614-1037-9_250.
  7. ^ a b Vorona, Elena; Zitzmann, Michael; Gromoll, Jörg; Schüring, Andreas N.; Nieschlag, Eberhard (2007-09-01). "Clinical, Endocrinological, and Epigenetic Features of the 46,XX Male Syndrome, Compared with 47,XXY Klinefelter Patients". The Journal of Clinical Endocrinology & Metabolism. 92 (9): 3458–3465. doi:10.1210/jc.2007-0447. ISSN 0021-972X.
  8. ^ Lisker, R; Flores, F; Cobo, A; Rojas, F G (December 1970). "A case of XX male syndrome". Journal of Medical Genetics. 7 (4): 394–398. ISSN 0022-2593. PMC 1468937. PMID 5501706.{{cite journal}}: CS1 maint: PMC format (link)
  9. ^ a b Lisker, R; Flores, F; Cobo, A; Rojas, F G (December 1970). "A case of XX male syndrome". Journal of Medical Genetics. 7 (4): 394–398. ISSN 0022-2593. PMC 1468937. PMID 5501706.{{cite journal}}: CS1 maint: PMC format (link)
  10. ^ Abusheikha, N.; Lass, A.; Brinsden, P. (2001-04-01). "XX males without SRY gene and with infertility: Case report". Human Reproduction. 16 (4): 717–718. doi:10.1093/humrep/16.4.717. ISSN 0268-1161.
  11. ^ Vorona, Elena; Zitzmann, Michael; Gromoll, Jörg; Schüring, Andreas N.; Nieschlag, Eberhard (2007-09-01). "Clinical, Endocrinological, and Epigenetic Features of the 46,XX Male Syndrome, Compared with 47,XXY Klinefelter Patients". The Journal of Clinical Endocrinology & Metabolism. 92 (9): 3458–3465. doi:10.1210/jc.2007-0447. ISSN 0021-972X.
  12. ^ Chen, Harold (2012). "XX Male". Atlas of Genetic Diagnosis and Counseling: 2191–2196. doi:10.1007/978-1-4614-1037-9_250.
  13. ^ Margarit, Ester; Coll, M. Dolors; Oliva, Rafael; Gómez, David; Soler, Anna; Ballesta, Francisca (2000-01-03). "SRY gene transferred to the long arm of the X chromosome in a Y-positive XX true hermaphrodite". American Journal of Medical Genetics. 90 (1): 25–28. doi:10.1002/(SICI)1096-8628(20000103)90:13.0.CO;2-5. ISSN 1096-8628.
  14. ^ Vetro, Annalisa; Ciccone, Roberto; Giorda, Roberto; Patricelli, Maria Grazia; Mina, Erika Della; Forlino, Antonella; Zuffardi, Orsetta (2011-01-01). "XX males SRY negative: a confirmed cause of infertility". Journal of Medical Genetics: jmedgenet–2011–100036. doi:10.1136/jmedgenet-2011-100036. ISSN 0022-2593. PMID 21653197.
  15. ^ Rajender, S. (2006-05-01). "SRY-negative 46,XX male with normal genitals, complete masculinization and infertility". Molecular Human Reproduction. 12 (5): 341–346. doi:10.1093/molehr/gal030. ISSN 1360-9947.
  16. ^ Swain, Amanda; Narvaez, Veronica; Burgoyne, Paul; Camerino, Giovanna; Lovell-Badge, Robin (1998-02-19). "Dax1 antagonizes Sry action in mammalian sex determination". Nature. 391 (6669): 761–767. doi:10.1038/35799. ISSN 1476-4687.
  17. ^ a b c Domenice, S.; Corrêa, R. V.; Costa, E. M. F.; Nishi, M. Y.; Vilain, E.; Arnhold, I. J. P.; Mendonca, B. B. (January 2004). "Mutations in the SRY, DAX1, SF1 and WNT4 genes in Brazilian sex-reversed patients". Brazilian Journal of Medical and Biological Research. 37 (1): 145–150. doi:10.1590/S0100-879X2004000100020. ISSN 0100-879X.

External links

Retrieved from "https://en.wikipedia.org/w/index.php?title=XX_male_syndrome&oldid=812657624"