XX male syndrome

Last updated
XX male syndrome
Other namesDe la Chapelle syndrome [1]
Human karyotype (259 34) Karyotype Human 46,XX (woman).jpg
Human karyotype 46 XX
Specialty Medical genetics   OOjs UI icon edit-ltr-progressive.svg

XX male syndrome, also known as de la Chapelle syndrome, is a rare condition in which an individual with a 46,XX karyotype develops a male phenotype. [2] Synonyms for XX male syndrome include 46,XX testicular difference of sex development (or 46,XX DSD) [3] [4] [5] [6]

Contents

In 90 percent of these individuals, the syndrome is caused by the Y chromosome's SRY gene, which triggers male reproductive development, being atypically included in the crossing over of genetic information that takes place between the pseudoautosomal regions of the X and Y chromosomes during meiosis in the father. [2] [7] When the X with the SRY gene 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. [2] The masculinization of XX males is variable.

This syndrome is diagnosed through various detection methods and occurs in approximately 1:20,000 newborn males, making it much less common than  Klinefelter syndrome. [2] [8] [9] Medical treatment of the condition varies, with medical treatment usually not necessary. [1] [10] The alternative name for XX male syndrome refers to Finnish scientist Albert de la Chapelle, who studied the condition and its etiology. [11]

Signs and symptoms

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. [12] External genital ambiguities can include hypospadias, micropenis, and clitoromegaly only in SRY negative XX male syndrome. [12] Typically, the appearance of XX males differs from that of an XY male in that they are smaller in height and weight. [2] Most XX males have small  testes, and have an increase in maldescended testicles compared to XY males. All are believed to be sterile, case studies of XX males have revealed all XX males were infertile and most were hypogonadal individuals; One case control study[ which? ] conclusion discloses that they could not make the assumption that all XX male syndrome individuals in the World presented the same characteristic as the 11 individuals they tested. The author explains that the limitation in sample size could be a flaw of the study results, hence stating they could not disregard the possibility a fertile XX male syndrome could exist in the population. It is important to point out that the author's hypothesis in which a possible fertile XX male would exist was loosely expressed and it appears to be a personal opinion of the author, no factual or scientific data was included with the claim and it is in complete contradiction with the presented case study findings. Another study of an XX Male revealed a testicular biopsy findings to be: diffuse interstitial fibrosis, tubular fibrosis, and azoospermia [2] [13] Some XX male individuals have decreased amounts of body hair and decreased libido. [13] Individuals with this condition sometimes have feminine characteristics, with varying degrees of  gynecomastia  but with no intra-abdominal  Müllerian tissue. [13] 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. [14]

They generally have small testes and may also have abnormalities such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). A small number of affected people have external genitalia that do not look clearly male or clearly female (ambiguous genitalia). [3]

Masculinization

Schematic of sexual differentiation in humans Sex-diff.jpg
Schematic of sexual differentiation in humans

The degree to which individuals with XX male syndrome develop the male phenotype is variable, even among SRY-positive individuals. [15] A completely male phenotype usually develops in the presence of the SRY gene but, in some cases, the presence of the SRY gene can result in internal and/or external genitalia ambiguities. [15] Normal XX females undergo X inactivation during which one copy of the X chromosome is silenced. It is thought that X inactivation in XX males may account for the genital ambiguities and incomplete masculinization seen in SRY-positive XX males. [16] [15] The X chromosome with the SRY gene is preferentially chosen to be the active X chromosome 90% of the time, which explains complete male phenotype being observed often in SRY-positive XX males. [16] [15] In the remaining 10%, X inactivation spreads to include a portion of the SRY gene, resulting in incomplete masculinization. [16] [15]

Masculinization of SRY-negative XX males is dependent upon which genes have mutations and at what point in development these mutations occur. [17]

Genetics

SRY Protein PBB Protein SRY image.jpg
SRY Protein

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 (the SRY gene) from the Y chromosome; this gene causes them to develop a male phenotype despite having chromosomes more typical of females. [2] Some XX males, however, do not have the SRY gene (SRY-negative) and the male phenotype may be caused by another gene on one of the autosomes.[ citation needed ]

SRY-positive

An example of translocation between two chromosomes Translocation of chromosomes (close-up) illustration.jpg
An example of translocation between two chromosomes

The SRY gene, normally found on the Y chromosome, plays an important role in sex determination by initiating testicular development. In about 80 percent of XX males, the SRY gene is present on one of the X chromosomes. [18] [19]

The condition results from an abnormal exchange of genetic material between chromosomes (translocation). This exchange occurs as a random event during the formation of sperm cells in the affected person's father. The tip of the Y chromosome contains the SRY gene and, during recombination, a translocation occurs in which the SRY gene becomes part of the X chromosome. [12] [20] If a fetus is conceived from a sperm cell with an X chromosome bearing the SRY gene, it will develop as a male despite not having a Y chromosome. This form of the condition is called SRY-positive 46,XX testicular disorder of sex development. [3]

SRY-negative

About 20 percent of those with 46 XX testicular disorder of sex development do not have the SRY gene. This form of the condition is called SRY-negative 46,XX testicular disorder of sex development. The cause of the disorder in these individuals is often unknown, although changes affecting other genes have been identified. Individuals with SRY-negative 46,XX testicular disorder of sex development are more likely to have ambiguous genitalia than are people with the SRY-positive form. [3] [2]

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. [21] [17] Another proposed cause is mutations to the DAX1 gene, which encodes a nuclear hormone receptor. [22] [23] DAX1 represses masculinizing genes; therefore, if there is a loss of function of DAX1, then testes can develop in an XX individual. [23] Mutations in SF1 and WNT4 genes have also been studied in connection with SRY-negative XX male syndrome. [23]

Diagnosis

In cases where the individual is being evaluated for ambiguous genitalia, such as a small phallus, hypospadias, or labioscrotal folds, exploratory surgery may be used to determine if male and/or female internal genitalia is present. [24] Indicators include two testes which have not descended the inguinal canal, although this is seen in a minority of XX males, and the absence of Müllerian tissue. [13] External indicators include decreased body weight and small testes. [2]

A standard karyotype can be completed to cytogenetically determine that an individual with a partial or complete male phenotype has an XX genotype. [12] [24] [25]

The presence and location of the SRY gene can by determined using fluorescence in situ hybridization (FISH). [2] [15]

Treatment

Genital ambiguities, while not necessary to treat for medical reasons, can be treated with hormonal therapy, surgery, or both. Since XX male syndrome is variable in its presentation, the specifics of treatment varies widely as well. In some cases, gonadal surgery can be performed to remove partial or whole female genitalia. This may be followed by plastic and reconstructive surgery to make the individual appear more externally male. [26] Conversely, the individual may wish to become more feminine and feminizing genitoplasty can be performed to make the ambiguous genitalia appear more female. [27] Hormonal therapy may also aid in making an individual appear more male or female. [26] [27]

Testosterone

Testosterone Testosteron.svg
Testosterone

At puberty, most affected individuals require treatment with the male sex hormone testosterone to induce development of male secondary sex characteristics such as facial hair and deepening of the voice (masculinization). Hormone treatment can also help prevent breast enlargement (gynecomastia). Adults with this disorder are usually shorter than average for males and are unable to have children (infertile). [3]

Epidemiology

As of 2010, only 200 cases have been reported — it is estimated that 1 of every 20,000 to 30,000 males has a 46,XX karyotype, making it much less common than other related syndromes, such as Klinefelter syndrome. [28] [29] [3]

See also

Related Research Articles

<span class="mw-page-title-main">5α-Reductase 2 deficiency</span> Medical condition

5α-Reductase 2 deficiency (5αR2D) is an autosomal recessive condition caused by a mutation in SRD5A2, a gene encoding the enzyme 5α-reductase type 2 (5αR2). The condition is rare, affects only genetic males, and has a broad spectrum.

<span class="mw-page-title-main">XY sex-determination system</span> Method of determining sex

The XY sex-determination system is a sex-determination system used to classify many mammals, including humans, some insects (Drosophila), some snakes, some fish (guppies), and some plants. In this system, the sex of an individual is determined by a pair of sex chromosomes. Females have two of the same kind of sex chromosome (XX), and are called the homogametic sex. Males have two different kinds of sex chromosomes (XY), and are called the heterogametic sex.

<span class="mw-page-title-main">Androgen insensitivity syndrome</span> Medical condition

Androgen insensitivity syndrome (AIS) is a condition involving the inability to respond to androgens, typically due to androgen receptor dysfunction.

<span class="mw-page-title-main">XY gonadal dysgenesis</span> Medical condition

XY complete gonadal dysgenesis, also known as Swyer syndrome, is a type of defect hypogonadism in a person whose karyotype is 46,XY. Though they typically have normal vulvas, the person has underdeveloped gonads, fibrous tissue termed "streak gonads", and if left untreated, will not experience puberty. The cause is a lack or inactivation of an SRY gene which is responsible for sexual differentiation. Pregnancy is often possible in Swyer syndrome with assisted reproductive technology. The phenotype is usually similar to Turner syndrome (45,X0) due to a lack of X inactivation. The typical medical treatment is hormone replacement therapy. The syndrome was named after Gerald Swyer, an endocrinologist based in London.

<span class="mw-page-title-main">Virilization</span> Biological development of male sex characteristics

Virilization or masculinization is the biological development of adult male characteristics in young males or females. Most of the changes of virilization are produced by androgens.

<span class="mw-page-title-main">Sex-determining region Y protein</span> Protein that initiates male sex determination in therian mammals

Sex-determining region Y protein (SRY), or testis-determining factor (TDF), is a DNA-binding protein encoded by the SRY gene that is responsible for the initiation of male sex determination in therian mammals. SRY is an intronless sex-determining gene on the Y chromosome. Mutations in this gene lead to a range of disorders of sex development with varying effects on an individual's phenotype and genotype.

<span class="mw-page-title-main">Ovotesticular syndrome</span> A condition where a person has a gonad that contains both ovarian and testicular tissue.

Ovotesticular syndrome is a rare congenital condition where an individual is born with both ovarian and testicular tissue. It is one of the rarest DSDs, with only 500 reported cases. Commonly, one or both gonads is an ovotestis containing both types of tissue. Although it is similar in some ways to mixed gonadal dysgenesis, the conditions can be distinguished histologically.

<span class="mw-page-title-main">Genital ridge</span>

The genital ridge is the precursor to the gonads. The genital ridge initially consists mainly of mesenchyme and cells of underlying mesonephric origin. Once oogonia enter this area they attempt to associate with these somatic cells. Development proceeds and the oogonia become fully surrounded by a layer of cells.

<span class="mw-page-title-main">XXYY syndrome</span> Extra X and Y chromosome in males

XXYY syndrome is a sex chromosome anomaly in which males have 2 extra chromosomes, one X and one Y chromosome. Human cells usually contain two sex chromosomes, one from the mother and one from the father. Usually, females have two X chromosomes (XX) and males have one X and one Y chromosome (XY). The appearance of at least one Y chromosome with a properly functioning SRY gene makes a male. Therefore, humans with XXYY are genotypically male. Males with XXYY syndrome have 48 chromosomes instead of the typical 46. This is why XXYY syndrome is sometimes written as 48, XXYY syndrome or 48, XXYY. It affects an estimated one in every 18,000–40,000 male births.

<span class="mw-page-title-main">Gonadal dysgenesis</span> Congenital disorder of the reproductive system

Gonadal dysgenesis is classified as any congenital developmental disorder of the reproductive system in humans. It is atypical development of gonads in an embryo. One type of gonadal dysgenesis is the development of functionless, fibrous tissue, termed streak gonads, instead of reproductive tissue. Streak gonads are a form of aplasia, resulting in hormonal failure that manifests as sexual infantism and infertility, with no initiation of puberty and secondary sex characteristics.

<span class="mw-page-title-main">Sex chromosome</span> Chromosome that differs from an ordinary autosome in form, size, and behavior

Sex chromosomes are chromosomes that carry the genes that determine the sex of an individual. The human sex chromosomes are a typical pair of mammal allosomes. They differ from autosomes in form, size, and behavior. Whereas autosomes occur in homologous pairs whose members have the same form in a diploid cell, members of an allosome pair may differ from one another.

<span class="mw-page-title-main">Sexual differentiation in humans</span> Process of development of sex differences in humans

Sexual differentiation in humans is the process of development of sex differences in humans. It is defined as the development of phenotypic structures consequent to the action of hormones produced following gonadal determination. Sexual differentiation includes development of different genitalia and the internal genital tracts and body hair plays a role in sex identification.

<span class="mw-page-title-main">Disorders of sex development</span> Medical conditions involving the development of the reproductive system

Disorders of sex development (DSDs), also known as differences in sex development or variations in sex characteristics (VSC), are congenital conditions affecting the reproductive system, in which development of chromosomal, gonadal, or anatomical sex is atypical.

<span class="mw-page-title-main">Steroidogenic factor 1</span> Protein-coding gene in humans

The steroidogenic factor 1 (SF-1) protein is a transcription factor involved in sex determination by controlling the activity of genes related to the reproductive glands or gonads and adrenal glands. This protein is encoded by the NR5A1 gene, a member of the nuclear receptor subfamily, located on the long arm of chromosome 9 at position 33.3. It was originally identified as a regulator of genes encoding cytochrome P450 steroid hydroxylases, however, further roles in endocrine function have since been discovered.

<span class="mw-page-title-main">Klinefelter syndrome</span> Human chromosomal condition

Klinefelter syndrome (KS), also known as 47,XXY, is a chromosome anomaly where a male has an extra X chromosome. These complications commonly include infertility and small, poorly functioning testicles. These symptoms are often noticed only at puberty, although this is one of the most common chromosomal disorders, occurring in one to two per 1,000 live births. It is named after American endocrinologist Harry Klinefelter, who identified the condition in the 1940s.

46,XX/46,XY is a chimeric genetic condition characterized by the presence of some cells that express a 46,XX karyotype and some cells that express a 46,XY karyotype in a single human being. The cause of the condition lies in utero with the aggregation of two distinct blastocysts or zygotes into a single embryo, which subsequently leads to the development of a single individual with two distinct cell lines, instead of a pair of fraternal twins. 46,XX/46,XY chimeras are the result of the merging of two non-identical twins. This is not to be confused with mosaicism or hybridism, neither of which are chimeric conditions.

45,X/46,XY mosaicism, also known as X0/XY mosaicism and mixed gonadal dysgenesis, is a mutation of sex development in humans associated with sex chromosome aneuploidy and mosaicism of the Y chromosome. It is a fairly rare chromosomal disorder at birth, with an estimated incidence rate of about 1 in 15,000 live births. Mosaic loss of the Y chromosome in previously non-mosaic men grows increasingly common with age.

Albert Fredrik de la Chapelle, MD, Ph.D was a Finnish human geneticist, long-time head of Finland's first Department of Medical Genetics at the University of Helsinki, and subsequently professor of Human Cancer Genetics at Ohio State University. He was best known for his role in the elucidation of the genetics of hereditary colorectal cancer and Lynch syndrome.

Sexual anomalies, also known as sexual abnormalities, are a set of clinical conditions due to chromosomal, gonadal and/or genitalia variation. Individuals with congenital (inborn) discrepancy between sex chromosome, gonadal, and their internal and external genitalia are categorised as individuals with a disorder of sex development (DSD). Afterwards, if the family or individual wishes, they can partake in different management and treatment options for their conditions.

<span class="mw-page-title-main">Definitions of intersex</span>

Various criteria have been offered for the definition of intersex, including ambiguous genitalia, atypical genitalia, and differential sexual development. Ambiguous genitalia occurs in roughly 0.05% of all births, and atypical genitalia occurs in 0.5% of all births, usually caused by masculinization or feminization during pregnancy, these conditions range from full androgen insensitivity syndrome to ovotesticular syndrome, although the definition of what constitutes "normal" genitalia is largely arbitrary.

References

  1. 1 2 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.
  2. 1 2 3 4 5 6 7 8 9 10 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. PMID   17579198.
  3. 1 2 3 4 5 6 "46,XX testicular disorder of sex development - Genetics Home Reference". Archived from the original on 2019-05-17. Retrieved 2017-01-08.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  4. ↑ RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: 46,XX testicular disorder of sex development". www.orpha.net. Archived from the original on 2017-01-13. Retrieved 2017-01-12.{{cite web}}: CS1 maint: numeric names: authors list (link)
  5. ↑ Délot, EC; Vilain, EJ; Pagon, RA; Adam, MP; Ardinger, HH; Wallace, SE; Amemiya, A; Bean, LJH; Bird, TD; Fong, CT; Mefford, HC; Smith, RJH; Stephens, K (1993). "Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development". Nonsyndromic 46,XX Testicular Disorders of Sex Development. University of Washington, Seattle. PMID   20301589. Archived from the original on 18 January 2017. Retrieved 12 January 2017.{{cite book}}: |journal= ignored (help)updated 2015
  6. ↑ "46,XX testicular disorder of sex development: MedlinePlus Genetics". medlineplus.gov. Archived from the original on 2020-09-15. Retrieved 2020-09-06.
  7. ↑ Andersson, M.; Page, D. C.; de la Chapelle, A. (1986-08-15). "Chromosome Y-specific DNA is transferred to the short arm of X chromosome in human XX males". Science. 233 (4765): 786–788. Bibcode:1986Sci...233..786A. doi:10.1126/science.3738510. ISSN   0036-8075. PMID   3738510. S2CID   32456133.
  8. ↑ Anık, Ahmet; Çatlı, Gönül; Abacı, Ayhan; Böber, Ece (2013). "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.
  9. ↑ 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 (2): 46–48. doi:10.4274/Tjem.2064.
  10. ↑ 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.
  11. ↑ de la Chapelle, Albert (August 1981). "The etiology of maleness in XX men". Human Genetics. 58 (1): 105–116. doi:10.1007/bf00284157. ISSN   0340-6717. PMID   6945286. S2CID   26425178.
  12. 1 2 3 4 Chen, Harold (2012). "XX Male". Atlas of Genetic Diagnosis and Counseling. pp. 2191–2196. doi:10.1007/978-1-4614-1037-9_250. ISBN   978-1-4614-1036-2.
  13. 1 2 3 4 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. doi:10.1136/jmg.7.4.394. ISSN   0022-2593. PMC   1468937 . PMID   5501706.
  14. ↑ 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. PMID   11278224.
  15. 1 2 3 4 5 6 Kusz, Kamila; Kotecki, Maciej; Wojda, Alina; Szarras-Czapnik, Maria; Latos-Bielenska, Anna; Warenik-Szymankiewicz, Alina; Ruszczynska-Wolska, Anna; Jaruzelska, Jadwiga (1999-06-01). "Incomplete masculinisation of XX subjects carrying the SRY gene on an inactive X chromosome". Journal of Medical Genetics. 36 (6): 452–456. doi:10.1136/jmg.36.6.452. ISSN   0022-2593. PMC   1734388 . PMID   10874632.
  16. 1 2 3 Bouayed Abdelmoula, Nouha; Portnoi, Marie-France; Keskes, Leila; Recan, Dominique; Bahloul, Ali; Boudawara, Tahia; Saad, Ali; Rebai, Tarek (2003-01-01). "Skewed X-chromosome inactivation pattern in SRY positive XX maleness: a case report and review of literature". Annales de Génétique. 46 (1): 11–18. doi:10.1016/S0003-3995(03)00011-X. PMID   12818524.
  17. 1 2 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. PMID   16556678.
  18. ↑ Majzoub, Ahmad; Arafa, Mohamed; Starks, Christopher; Elbardisi, Haitham; Al Said, Sami; Sabanegh, Edmund (2017). "46 XX karyotype during male fertility evaluation; case series and literature review". Asian Journal of Andrology. 19 (2): 168–172. doi: 10.4103/1008-682X.181224 . ISSN   1745-7262. PMC   5312213 . PMID   27297128.
  19. ↑ Anık, Ahmet; Çatlı, Gönül; Abacı, Ayhan; Böber, Ece (2013-12-10). "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.
  20. ↑ 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)90:1<25::aid-ajmg5>3.0.co;2-5. ISSN   1096-8628. PMID   10602113.
  21. ↑ 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. 48 (10): jmedgenet–2011–100036. doi:10.1136/jmedgenet-2011-100036. ISSN   0022-2593. PMC   3178810 . PMID   21653197.
  22. ↑ 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. Bibcode:1998Natur.391..761S. doi:10.1038/35799. ISSN   1476-4687. PMID   9486644. S2CID   4416667.
  23. 1 2 3 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. PMID   14689056.
  24. 1 2 "OMIM Entry - # 400045 - 46,XX SEX REVERSAL 1; SRXX1". www.omim.org. Archived from the original on 2019-12-13. Retrieved 2017-11-07.
  25. ↑ Délot, Emmanuèle C; Vilain, Eric J (2003). "Nonsyndromic 46,XX Testicular Disorders/Differences of Sex Development". Nonsyndromic 46,XX Testicular Disorders of Sex Development. University of Washington, Seattle. PMID   20301589. Archived from the original on 23 June 2020. Retrieved 6 December 2018.{{cite book}}: |journal= ignored (help)
  26. 1 2 Parada-Bustamante, Alexis; Ríos, Rafael; Ebensperger, Mauricio; Lardone, María Cecilia; Piottante, Antonio; Castro, Andrea (2010-11-01). "46,XX/SRY-negative true hermaphrodite". Fertility and Sterility. 94 (6): 2330.e13–2330.e16. doi: 10.1016/j.fertnstert.2010.03.066 . ISSN   0015-0282. PMID   20451191. Archived from the original on 2019-12-13. Retrieved 2017-11-29.
  27. 1 2 Kurita, Masakazu; Aiba, Emiko; Matsumoto, Daisuke; Sato, Katsujiro; Nagase, Takashi; Yoshimura, Kotaro (May 2006). "Feminizing genitoplasty for treatment of XX male with masculine genitalia". Plastic and Reconstructive Surgery. 117 (6): 107e–111e. doi:10.1097/01.prs.0000214653.30135.a1. ISSN   1529-4242. PMID   16651931.
  28. ↑ Bouvattier, Claire (1 January 2010). "Disorders of Sex Development". Pediatric Urology (Second Edition). W.B. Saunders: 459–475. doi:10.1016/B978-1-4160-3204-5.00035-9. ISBN   9781416032045.
  29. ↑ Witchel, Selma Feldman; Topaloglu, A. Kemal (1 January 2019). "Chapter 17 - Puberty: Gonadarche and Adrenarche". Yen and Jaffe's Reproductive Endocrinology (Eighth Edition). Content Repository Only!: 394–446.e16. doi:10.1016/B978-0-323-47912-7.00017-2. ISBN   9780323479127. S2CID   239351840. Archived from the original on 17 May 2019. Retrieved 21 March 2020.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.