The complete androgen insensitivity syndrome ( CAIS ) is a condition that causes the cell's inability to respond to androgens. Thus, insensitivity to androgens is only clinically significant when it occurs in genetic men (ie individuals with Y chromosomes, or more specifically, the SRY genes). Cell imbalance in the presence of androgenic hormone prevents masculinisation of male genitalia in developing fetuses, as well as the development of secondary sexual characteristics of men during puberty, but enables, without significant disruption, genital and sexual development of women in genetics. the man with the condition.
Although all human fetuses, both male and female genetically, initiate fetal development appear to be similar, with the Müllüllerian (female) duct system and the Wolffia (male) duct system developing. In the seventh week of pregnancy that an unaffected genetic male body begins their masculinization: that is, the Wolffia duct system is promoted and the Mullerian duct system is suppressed (as opposed to normal females). This process is triggered by the androgens produced by the gonads, which in the genetic woman had previously become an ovary, but in genetic men have become testicles because of the Y chromosome. The male cells that are not affected are then obscured by, inter alia, enlarges the genital tubercle into the penis but in the woman becomes the clitoris, whilst what in the female becomes the fetal labia to become the male scrotum (where the testes will come down).
Individual men affected by CAIS, however, will develop a normal external female habitus, although there is a Y chromosome, but internally, they will lack utero, and the vaginal cavity will be shallow, while the gonads, which have been turned into testicles rather than ovaries in a separate process previously also triggered by their Y chromosome, will still not go down in the place where the ovaries will be located. This not only causes male genital insufficiency with CAIS, but also presents the risk of testicular cancer later in life.
CAIS is one of three categories of androgen insensitivity syndrome (AIS) because AIS is distinguished by the degree of genital masculinity: complete androgen insensitivity syndrome (CAIS) when external genitalia is a mild androgen insensitivity syndrome in normal women (MAIS). ) when external genitalia is partial androgen insensitivity syndrome and normal men, when external genitalia is in part, but not completely masculinized.
Androgen insensitivity syndrome is the largest single entity leading to 46, XY undermasculinization.
Video Complete androgen insensitivity syndrome
Signs and symptoms
Individuals with complete androgen insensitivity syndrome (grades 6 and 7 on the Quigley scale) were born as female phenotypes, without signs of genital masculinisation, despite having 46, XY karyotypes. CAIS symptoms do not appear until puberty, which may be slightly delayed, but otherwise normal except because no menstruation and secondary terminal hair is reduced or absent. Axillary hair (ie underarm hair) fails to develop in one-third of all cases. The external genitalia is normal, although the labia and clitoris are sometimes less developed. The depth of the vagina varies greatly, but is usually shorter than the unaffected woman; one study of eight women with CAIS measured average vaginal depth to 5.9 cm (vs. 11.1 Â ± 1.0 cm for unaffected women). In some extreme cases, the vagina has been reported aplastic (resembling a "dimple"), although this exact event is unknown.
Gonad in this woman is not an ovary, but on the contrary, is a testis; during the developmental stage of the embryo, the testes are formed in an androgen-independent process that occurs due to the influence of the SRY gene on the Y chromosome. They may lie intra-abdominally, in the internal inguinal ring, or perhaps herniate to the labia majora, on the condition discovery. Testes in affected women have been found to be atrophy in gonadectomy. Testosterone produced by the testes can not be directly used because of mutant androgen receptors that characterize CAIS; instead, aromatized into estrogen, which effectively feminizes the body and contributes to the normal female phenotype observed in CAIS.
The immature sperm cells in the testis do not mature through the early stages, since sensitivity to androgens is required for spermatogenesis to be completed. The risk of germ cell malignancy, once considered relatively high, is now estimated at about 2%. The structure of Wolffia (epididymide, vasa deferentia, and seminal vesicles) is usually absent, but will develop at least in part in about 30% of cases, depending on the mutations that cause CAIS. The prostate, such as the male external genitalia, can not masculinize in the absence of androgen receptor function, and thus remains in the female form.
The MÃÆ'¼llerian system (the fallopian tubes, uterus, and upper vagina) usually degenerates due to the anti-MÃÆ'¼llerian hormone derived from the testes Sertoli cells. These women are born without fallopian tubes, cervix, or uterus, and the vagina ends "blindly" in the bag. MÃÆ'¼llerian regression is not completely complete in about one third of all cases, resulting in "remnants" MÃÆ'¼llerian. Although rare, some cases of women with CAIS and fully developed MÃÆ'¼llerian structures have been reported. In one exceptional case, a 22-year-old boy with CAIS was found to have normal cervix, uterus, and fallopian tubes. In an unrelated case, a fully developed uterus was found in a 22-year-old adult with CAIS.
Other subtle differences that have been reported include longer limbs and legs and larger hands due to higher stature than unaffected women, larger teeth, minimal or no acne, well-developed breasts, and more incidents large from meibom gland dysfunction (ie dry eye syndrome and light sensitivity).
Comorbidity
All forms of androgen insensitivity, including CAIS, are associated with infertility, although exceptions have been reported for both mild and partial forms.
CAIS is associated with decreased bone mineral density. Some people hypothesize that the decrease in bone mineral density observed in women with CAIS is associated with inadequate time of gonadotomy and estrogen supplementation. However, recent studies have shown that bone mineral density is similar to whether gonadectomy occurs before or after puberty, and decreases despite estrogen supplementation, leading to some hypotheses that this deficiency is directly due to the role of androgens in bone mineralization.
CAIS is also associated with an increased risk for gonadal tumors (eg germ cell malignancies) in adulthood if gonadectomy is not performed. The risk of malignant germ cell tumors in women with CAIS increases with age and is estimated to be 3.6% at 25 years and 33% at 50 years. The incidence of gonadal tumors in childhood was considered relatively low; A recent review of the medical literature found that only three cases of malignant germ cell tumors in preteen girls were reported to work with CAIS in the last 100 years. Some estimate the incidence of germ cell malignancy to be as low as 0.8% before puberty.
Hypoplastic vagina, a relatively frequent finding in CAIS and some forms of PAIS, is associated with sexual difficulties including difficulty of vaginal penetration and dyspareunia.
At least one study showed that individuals with intersex conditions may be more susceptible to psychological difficulties, at least in part to parental attitudes and behavior, and conclude that the prevention of long-term psychological counseling for parents as well as for affected individuals should begin at the time of diagnosis.
Age is not considered to be influenced by SIA.
Maps Complete androgen insensitivity syndrome
Diagnosis
CAIS can only be diagnosed in normal phenotypic women. It is usually not suspected unless the menses fail to develop at puberty, or the inguinal hernia occurs during premenarche. As many as 1-2% of prepubertal girls who come with inguinal hernia will also have CAIS.
The diagnosis of CAIS or Swyer syndrome can be performed in utero by comparing the karyotype obtained with amniocentesis with the fetal external genitalia during prenatal ultrasound. Many infants with CAIS do not experience normal and spontaneous neonatal testosterone surges, a fact that can be diagnostically exploited by obtaining luteinizing hormone and early testosterone measurements, followed by human chorionic gonadotropin (hGC) stimulation tests.
The main differences for CAIS are complete gonadal dysgenesis (Swyer syndrome) and MÃÆ'¼llerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome or MRKH). Both CAIS and Swyer syndromes are associated with 46, XY karyotype, whereas MRKH is not; MRKH can thus be ruled out by examining the presence of Y chromosomes, which can be performed either by in situ hybridization fluorescence analysis (FISH) or in full karyotype. Swyer syndrome is distinguished by poor breast development and shorter stature. The diagnosis of CAIS is confirmed when the sequence of androgen receptor (AR) genes expresses mutations, although up to 5% of individuals with CAIS have no AR mutation.
Until the 1990s, CAIS diagnosis was often hidden from affected individuals and/or families. It is a current practice to reveal genotypes at the time of diagnosis, especially when girls are exposed to at least adolescence. If the affected individual is a child or a baby, it is generally up to the parents, often together with a psychologist, to decide when to disclose the diagnosis.
Management
The management of SIA is currently limited to symptomatic management; methods for correcting damaged androgen receptor proteins resulting from AR gene mutations are currently unavailable. Management areas include sex work, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, and genetic and psychological counseling. Non-consensual interventions are still common, although the general awareness of the resulting psychological trauma increases.
Sex Sex work and sexuality
Most of the individuals with CAIS were raised as women. They are born as phenotypic women and almost always have a gender identity of heterosexual women; the incidence of homosexuality in women with CAIS is considered to be less of an unaffected woman. However, at least two case studies have reported the gender identity of men in individuals with CAIS.
Widening therapy
Most cases of vaginal hypoplasia associated with CAIS can be corrected using a non-surgical pressure dilation method. The elastic nature of the vaginal tissue, as demonstrated by its ability to accommodate the difference in size between the tampon, the penis, and the baby's head, makes widening possible even in cases where the vaginal depth is significantly compromised. Treatment compliance is considered very important to achieve satisfactory results. Widening can also be done through the Vecchietti procedure, which extends the vaginal tissue into a functional vagina using a traction tool that anchored to the abdominal wall, subperitoneal stitches, and mold placed against the vaginal lining. Vaginal stretching occurs by increasing the tension in the stitches, which are done daily. The current non-operative pressure widening method is recommended as a first choice, because it is not invasive, and is very successful. Vaginal dilatation should not be performed before puberty.
Gonadectomy
Although it is often recommended that women with CAIS end up undergoing gonadectomy to reduce the risk of cancer, there are differences of opinion regarding the need and timing of gonadectomy. The risk of malignant germ cell tumors in women with CAIS increases with age and is estimated to be 3.6% at 25 years and 33% at 50 years. However, only three cases of malignant germ cell tumors in preteen girls with CAIS have been reported in the last 100 years. The youngest of these girls is 14 years old. If gonadectomy is performed earlier, puberty should be artificially induced by a gradually increasing dose of estrogen. If gonadectomy is done late, then puberty will happen by itself, because the aromatization of testosterone becomes estrogen. At least one organization, the Australasian Pediatric Endocrine Group, classifies the cancer risk associated with CAIS as low enough to recommend against gonadectomy, although it warns that the risk of cancer still rises above the general population, and ongoing cancer monitoring is essential. Some choose to do gonadectomy if and when the inguinal hernia appears. Estrogen replacement therapy is essential to minimize bone mineral density shortages later in life.
Hormone replacement therapy
Some people hypothesize that the supraphysiological rate of estrogen can reduce the reduced bone mineral density associated with CAIS. Data have been published showing that women affected who are not in compliance with estrogen replacement therapy, or who have estrogen replacement hoses, have significantly decreased bone mineral density. Progestin replacement therapy is rarely started, because there is no uterus. Androgen replacement has been reported to improve the well-being of women who are gonadectomized with CAIS, although the mechanism by which these benefits are achieved is poorly understood.
Counseling
It is no longer a common practice to hide the diagnosis of CAIS from affected individuals or their families. Parents of children with CAIS need substantial support in planning and implementing disclosures for their children after diagnosis is established. For parents with young children, information disclosure is an ongoing collaborative process that requires an individualized approach that develops according to the child's cognitive and psychological development. In all cases, the help of an experienced psychologist in this field is recommended.
Neovaginal Construction
Many surgical procedures have been developed to create neovagina, because there is nothing ideal. Surgical intervention should only be considered after the non-surgical pressure dilation method fails to produce satisfactory results. Neovaginoplasty can be performed using a skin graft, intestinal segment, ileum, peritoneum, Interceed, buccal mucosa, amnion, or dura mater. The success of the method should be determined by the sexual function, and not only with the vagina, as has been done in the past. The ialal or cecal segment may be problematic because of the shorter mesenterium, which can produce tension in the neovagina, leading to stenosis. Sigmoid neovagina is considered to self-lubricate, without the production of excess mucus associated with small intestinal segments. Vaginoplasty can cause scarring of the introitus (opening of the vagina), which requires additional surgery to repair. The vaginal dilator is required postoperatively to prevent vaginal stenosis from scarring. Other complications include bladder and intestinal injury. Annual examination is necessary because neovaginoplasty carries the risk of carcinoma, although neovaginal carcinoma is rare. Both neovaginoplasty and vaginal dilatation should be performed before puberty.
Prognosis
The challenges presented to people affected by this condition include: psychologically coming to terms with conditions, difficulties with sexual function, infertility. Long-term studies show that with appropriate medical and psychological care, women with CAIS can be satisfied with their sexual function and psychosexual development. CAIS women can live an active life and expect a normal age.
See also
- complete estrogen insensitivity syndrome
References
External links
- Information
- androgen at NIH/UW GeneTests
- Australian parent/patient booklet on CAIS (archived)
- My Sex Secrets news articles
- Women With Male DNA All Women news articles on ABCnews.com
- Group of patients AIS Support Group AISSG (UK and International)
Source of the article : Wikipedia
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