Intersex is a group of individuals in whom there exists a discrepancy between the external genitalia and internal gonads (testes and ovary). In the earlier times these people were referred to as ‘hermaphrodites’
and the condition as hermophroditism. Taking into account the insensitivity and inaccuracy of this ancient term, these conditions are now referred to as ‘Disorders of Sex Development’ or DSD.
Intersex can be classified into four categories the details of which are discussed below.a) 46 XX Intersex
A person with this condition has the genotype of a female 46, XX. External genitalia will appear like that of a male. The labia of the female external genitalia gets fused and the clitoris is enlarged to look like a penis giving the appearance of male genitalia.
It must be noted that the person usually has a normal uterus, ovaries and fallopian tubes. Some of the causes include-
• Overexposure of a female fetus to excess male hormones while still in the mother’s womb. This may even be due to tumors producing male hormones in the mother.
• Aromatase deficiency- Aromatase is an enzyme that normally converts male hormones to female hormones. Excessive aromatase activity leads to the overproduction of female hormone estrogen while its deficiency can result in 46, XX intersex, where enough estrogen is not produced. This is not noticeable until puberty when these XX girls begin to display male characteristics.b) 46, XY Intersex
The 46, XY person has the genotype of a male but the external genitalia may resemble that of a female or it may be ambiguous or incompletely formed. Testes when present may be normal or malformed. In some cases it may be absent. The condition used to be called ‘male pseudohermaphroditism’.
It is also referred to 46, XY with undervirilization and it occurs due to the following possible causes:
• Testosterone formation is a multi-step process that requires the functioning of different enzymes. Dysfunction of these enzymes can result in its inadequate production and results in the formation of 46, XY intersex.
• In some cases of 46, XY intersex, normal internal testes may be present that ensures adequate testosterone production. However deficiency in the enzyme 5-alpha-reductase impairs the conversion of testosterone to dihydrotestosterone a step necessary for proper maleness to manifest.
• Malformation syndromes such as Smith Lemli –Opitz and Campomelic dysplasia also have 46 XY karyotype with female or ambiguous genitalia.These occur due to mutations in the autosomal genes DHCR7 (which codes for 7-dehydrocholesterol reductase) or it could be due to deletions in the autosomal gene SOX-9
• In some cases of 46XY there is a loss of SRY genes located on the Y chromosomes . These SRY genes are responsible for the development of the male attributes.
• Sometimes, in a 46 XY individual, a duplication of the dosage sensitive region (DSS) on the short arm of the X (Xp) results in female external genitalia.
• Mutation in the gene DAX 1 is also associated with XY females
• Swyer syndrome is a type of hypogonadism. Here the functional gonads,the ovaries, are absent but the person resembles a normal female and has a karyotype 46, XY.Androgen Insensitivity Syndrome(AIS) is the most common cause of 46, XY intersex. A person with AIS is insensitive to the male hormones( androgens). When an individual presents with a male genotype 46 XY but appears more like a female, a case of ‘Androgen Insensitivity Syndrome’, also known as ‘testicular feminization’ should be suspected .
AIS individuals produce adequate amounts of testosterone but they lack the receptors that sensitize the body to the male hormone androgen. As a result the person’s body cannot detect the androgens and, therefore, is unable to develop as male. These individuals grow as females and it really comes as a surprise to many of them when the abnormality is detected or when they find out that they are infertile.
c) True Gonadal Intersex.
A person is said to be true gonadal intersex when both testicular and ovarian tissues are present.These tissues may be found seperately or they may be present as a single ovotestis. The genotype may denote 46 XX, 46 XY or both. The external genitalia may appear to be male or female or it may be ambiguous . The underlying cause of this condition, once referred to as “true hermaphroditism”, is yet unknown.
d) Complex Intersex Disorders
These intersex disorders are chrecterized by the impaired sexual development and involves conditions such as Turners syndrome (45,XO), Klinefelter syndrome (47,XXY) and super females (47,XXX).These individuals are not classically intersex but display deficiencies in their overall sexual development.