XX male syndrome

XX male syndrome, also known as De la Chapelle syndrome, is a rare congenital intersex condition where an individual with a female genotype has phenotypically male characteristics that can vary among cases. In 90 percent of these individuals, the syndrome is caused by unequal crossing over between X and Y chromosomes during meiosis in the father. This results in the X chromosome containing the SRY gene, as opposed to the Y chromosome where it is normally found. 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. The masculinization of XX males is variable. XX male syndrome, also known as De la Chapelle syndrome, is a rare congenital intersex condition where an individual with a female genotype has phenotypically male characteristics that can vary among cases. In 90 percent of these individuals, the syndrome is caused by unequal crossing over between X and Y chromosomes during meiosis in the father. This results in the X chromosome containing the SRY gene, as opposed to the Y chromosome where it is normally found. 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. 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. Treatment is medically unnecessary, although some individuals choose to undergo treatments to make them appear more male or female. XX male syndrome is not to be confused with sex determination in some non-human mammal species that lack a Y chromosome at all, such as the Transcaucasian mole vole (Ellobius lutescens). 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). External genital ambiguities can include hypospadias, micropenis, and clitoromegaly. Typically, the appearance of XX males differs from that of an XY male in that they are smaller in height and weight. Most XX males have small testes, are sterile, and have an increase in maldescended testicles compared to XY males. Some XX male individuals have decreased amounts of body hair and decreased libido. Individuals with this condition sometimes have feminine characteristics, with varying degrees of gynecomastia but with no intra-abdominal Müllerian tissue. 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. The degree to which individuals with XX male syndrome develop the male phenotype is variable, even among SRY-positive individuals. 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. 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. 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. In the remaining 10%, X inactivation spreads to include a portion of the SRY gene, resulting in incomplete masculinization. Masculinization of SRY-negative XX males is dependent upon which genes have mutations and at what point in development these mutations occur. 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. 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. The presence of the translocated SRY gene leads to an XX embryo developing male characteristics. In 10 % of cases, an XX male does not have the SRY gene, causing variations in their levels of masculinity. 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. Another proposed cause is mutations to the DAX1 gene which encodes a nuclear hormone receptor. DAX1 represses masculinizing genes, therefore, if there is a loss of function of DAX1 then testes can develop in an XX individual. Mutations in SF1 and WNT4 genes are also being studied in connection with SRY-negative XX male syndrome.