Complete androgen insensitivity syndrome occurs when the body does not respond to androgens at all. It happens when there’s a defect or abnormality in the androgen receptor (AR) gene. Androgen insensitivity syndrome (AIS) is a rare condition that affects sexual development. People with AIS are genetically male, but don’t develop male external genitals because their bodies can’t respond to male sex hormones. Androgen insensitivity syndrome (AIS) is a rare, inherited, sexual development disorder. In PAIS patients, in general, gender identity aligned with both sex of rearing male or female (56). Molecular diagnosis is achieved in almost all patients with CAIS and in a lower frequency in PAIS individuals. Non-synonymous point mutations are the commonest AR defects reported in AIS. In MAIS, the diagnosis should be considered in cases of pubertal gynecomastia and male infertility. In PAIS, the diagnosis is usually at birth due to the atypical external genitalia. In CAIS, the diagnosis can be done intrauterus, at birth, childhood or after puberty. Gender change is very rarely described in CAIS and there are just four cases of gender change in individuals with CAIS (57). During male puberty, DHT promotes further growth of the penis and scrotum. DHT is essential for the formation of the male external genitalia, including the penis and scrotum, in a fetus. Unlike testosterone, DHT doesn’t play a significant role in maintaining male physiology in adulthood. Levels of DHT are naturally much higher in males because they naturally have more testosterone. This takes place in the genital skin and prostate in males and in the skin in females. As an adult, your body converts about 10% of your testosterone (the main androgen) into DHT each day. So far, some factors, as chronological age and gonadal location can influence GCTs development (41). The risk of GCTs development is related to the presence of a Y chromosome, but is not the same for the different etiologies of 46,XY DSD. The use of DHT in male PAIS has been tested (0.3 mg/kg of androstanolone gel 2.5% for 4 months) and mixed results were obtained following DHT therapy (38). In general, hormonal replacement is started at the age of years with oral or transdermal estrogen. When gonadectomy is performed before puberty, estrogen replacement is necessary to induce puberty. AR allelic variants in heterozygosis was also identified in some individuals with 47,XXY karyotype causing AIS (31). Interesting, a deletion of an entire exon (exon 4) was previously described in a phenotypic male with azoospermia (29). Rarely, synonymous allelic variants affecting splicing sites has been described in PAIS (27) and in CAIS individuals (28). Some individuals with CAIS or PAIS do not have any AR mutations despite clinical, hormonal, and histological features sufficient to warrant an AIS diagnosis; up to 5% of women with CAIS do not have an AR mutation, as well as between 27 and 72% of individuals with PAIS. Inheritance is typically maternal and follows an X-linked recessive pattern; individuals with a 46,XY karyotype always express the mutant gene since they have only one X chromosome, whereas 46,XX carriers are minimally affected. Androgen insensitivity syndrome is the largest single entity that leads to 46,XY undermasculinized genitalia. Overactive bladder syndrome (OAB) is a common medical condition that affects the urinary system. However, if it happens repeatedly, it can affect your sex life and self-esteem. Missense mutations that result in a single amino acid substitution are known to produce the most phenotypic diversity. The degree of variation, however, does not appear to be constant across all AR mutations, and is much more extreme in some. Unfortunately, little information regarding phenotype can be gleaned from precise knowledge of the AR mutation itself; the same AR mutation may cause significant variation in the degree of masculinization in different individuals, even among members of the same family. Some carriers have been noted to have slightly reduced body hair, delayed puberty, and/or tall stature, presumably due to skewed X-inactivation. Several case studies of fertile 46,XY males with AIS have been published, although this group is thought to be a minority. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. Specifically, the androgen receptor attaches (binds) to androgen hormones to form an androgen-receptor complex. Partial androgen insensitivity is thought to be at least as common as complete androgen insensitivity. They have male internal sex organs (testes) that are undescended, which means they are located in the pelvis or abdomen instead of outside the body. This gene provides instructions for making a protein called an androgen receptor. People with this form of the condition have external sex characteristics that are typical of females. The abnormal gene either blocks or partially blocks androgens. With AIS, the gene mutation prevents male genitals from developing in people who are genetically male. AIS happens due to genetic mutations, which are changes to genes that affect how they function.
