Testicular feminization syndrome (TFS), also known as androgen insensitivity syndrome (AIS), is the most common form of male pseudohermaphroditism. TFS is caused by mutations in the Androgen receptor (AR) gene, resulting in structural and functional abnormalities of the AR, causing the target tissues related to male sexual development to be insensitive to androgens, thus causing a total or partial loss of the normal biological effects of androgens, and thus affecting the patient’s development toward masculinity. TFS is an X-linked recessive disorder, and the incidence of TFS in newborn boys is 1/60,000-1/20,000. The embryo has a pair of undifferentiated gonads, two sets of germinal ducts and germinal sinuses at the stage of sex undifferentiation. The direction of sex development in the embryo depends on the sex chromosomes in the fertilized egg. If the fertilized egg contains a Y chromosome, the embryo will develop as a male baby, otherwise it will develop as a female baby. This is because the SRY gene, located on the Y chromosome, induces the undifferentiated gonads to develop into the testes. The embryonic testis in turn determines the development of the germinal ducts, a process that is regulated by a combination of two hormones, testosterone (produced by Leydig cells to promote Wolffian duct development) and a Mullerian duct inhibitor (produced by Sertoli cells to inhibit Mullerian duct development). The result is that the Wolffian ducts on both sides eventually become the epididymis, vas deferens, and seminal vesicles, while the Mullerian ducts degenerate. However, in the absence of these two testosterones, the Wolffian ducts will degenerate and the Mullerian ducts will develop into the fallopian tubes, uterus, and upper 2/3 of the vagina. with the development of the internal genitalia, the continuous secretion of androgens will guide the development of the external genitalia towards the male, otherwise, they will evolve towards the female. The external genitalia in the undifferentiated stage consist mainly of the genital nodes, the urogenital folds, and the labial-scrotal bullae. In males, due to the action of dihydrotestosterone (DHL), a derivative of testosterone, the genital nodules develop to form the head of the penis, the urogenital folds lengthen and fuse to form the body of the penis and urethra, and the labial-scrotal bulge fuses to form the scrotum. In females, the external genital development process is relatively insignificant, with the genital nodules forming the clitoris, the urogenital folds forming the labia minora, and the labial-scrotal bulge forming the labia majora. In addition, androgens are also involved in the development of male secondary sexual characteristics, such as skeletal maturation, beard and body hair growth, and spermatogenesis. However, all the effects of androgens require the involvement of the AR gene, which is located in Xq11-q12 and contains 8 exons encoding 919 amino acids. Exon 1 of the AR gene encodes its transcriptional activation region, exons 2 and 3 encode the DNA binding region, exon 4 at the 5′ end encodes the hinge region, and exon 4 at the 3′ end and exons 5 to 8 together encode the hormone binding region. There are more than 600 reported AR mutation loci, most of which can cause TFS, and only a few of them are associated with the development of prostate and breast cancer. Seventy percent of AR mutations run in families and are passed from mother to offspring as carriers. The AR gene has three characteristic functional domains: the N-terminal transcriptional activation region (NTD), the DNA-binding region (DBD), and the c-terminal hormone-binding region (LBD). the LBD region is a key structure for binding androgens and is involved in nuclear localization, receptor dimerization, and protein-protein interactions, and is encoded by exon 4, end 3, and exons 5 to 8. the AR gene has one of the highest rates of mutations in The AR gene is one of the most mutated steroid hormone receptors, and most mutations can affect receptor-ligand binding or result in loss of transcriptional activation potential of the receptor-androgen complex. Among the more than 600 mutations identified so far, mutations include point mutations, deletions, insertions and shear point mutations, among which single base substitutions predominate and more than half of them occur in the LBD, about 20% in the DBD and about 15% in the NTD. AR is a member of the nuclear receptor superfamily, located in the cytoplasm, and is a ligand-dependent transcription factor that is associated with two major androgens in the human body, testosterone and testosterone. Testosterone and dihydrotestosterone (DHL), the two major androgens in the body, to perform different biological functions. The receptor-testosterone complex initiates Wolffian duct differentiation during embryonic life and regulates luteinizing hormone (LH) secretion and spermatogenesis; the main role of the receptor-DHL complex is to promote the development of external reproductive organs and prostate during embryonic life, as well as to participate in the development of secondary sexual characteristics during puberty. When AR dimerizes upon binding to androgens and translocates into the nucleus of target cells, it can regulate gene transcription when bound to the promoter region or regulatory region specific sequences of genes downstream of androgens, thus triggering a series of cascade responses related to male sexual differentiation. In the embryonic stage, testosterone secreted by Leydig cells in the testis of TFS patients is unable to stimulate the development of Wolffian ducts to form the male internal genitalia due to abnormal AR. In contrast, dihydrotestosterone likewise does not act on the urogenital sinuses and external genitalia, leading to their differentiation into the female vulva and lower vaginal segment. At the same time, testicular Sertoli cells secrete normal Mullerian duct inhibitory substances, which inhibit the proliferation of the Mullerian duct epithelium, causing it to degenerate and prevent the development of the fallopian tubes, uterus, cervix, and upper vaginal segment, ultimately leading to the formation of male pseudohermaphroditism. Depending on the degree of androgen receptor deficiency, patients may present with a wide range of male pseudohermaphroditism from a completely female phenotype, with hypospadias or micropenis, to a normal male phenotype with only sterility or mammary gland development. In addition, other factors such as embryonic androgen levels, the length of the CAG repeat sequence in exon 1, the interaction between AR and other co-transcription factors, somatic chimerism, and 5α-reductase activity can all influence the final phenotype of TFS patients. According to the degree of androgen receptor defects in the body, TFS can be classified into two types: complete and incomplete. Although both types are hereditary, only one type of defect is produced in a family, and clinical examination reveals testicular and epididymal tissues. Patients with the incomplete type are often female by gender and present with primary amenorrhea, rough skin, higher than average female stature, varying degrees of breast development, male nipples, absence of uterus and fallopian tubes, varying degrees of deformity in vulvar development, a little pubic hair, an enlarged clitoris, and a urethra located below the clitoris. The vagina was short and shallow or showed urogenital sinus. The testicular tissue was usually located on both sides of the labia, inguinal or abdominal inguinal ring, etc. Pathological examination showed atrophy of the varicocele, severe degeneration, atresia of the lumen, loss of supporting cells and germ cells, thickening of the basement membrane with vitelliform changes, and large sheets of interstitial cells. It is sensitive to exogenous androgens. In contrast, complete type patients have delicate skin, the same figure as the average female, well-developed breasts, female physique and female vulva, infantile female genitalia, labia are often poorly developed, clitoris is not enlarged, lower two-thirds of the vagina is well developed, so the depth is shallower than normal, its tip is blind end, no uterus, pelvic cavity is empty, pubic hair, axillary hair is sparse, testicular tissue is mostly located in the groin or in the abdominal cavity, pathological examination shows: light microscopy The pathological examination showed that: the varicocele was well developed, spermatocytes were occasionally seen, supporting cells and spermatocytes were not seen, the basement membrane was not thickened and glassy, and the interstitial cells were few in number, scattered or distributed in small clusters. There was no thickening of the basement membrane or vitreous changes. TFS patients had a karyotype of 46, XY, negative chromatin on oral mucosa examination and positive fluorescent vesicles (Y chromatin). Blood testosterone levels were normal or higher than normal male, estrogen levels were equivalent to follicular phase, and vaginal exfoliative cell examination showed estrogen levels equivalent to follicular phase of the menstrual cycle. Pelvic insufflation angiography, ultrasound and laparoscopy show an empty pelvis with no uterus or ovaries, and there may be intra-abdominal testes. In pregnant women with a family history of TFS, amniotic fluid or chorionic villus examination should be performed in early or mid-pregnancy, and if the fetal karyotype is 46,XY, ultrasound, amniocentesis, fetoscopy or magnetic resonance imaging should be given in mid-pregnancy to observe the development of the external genitalia of the fetus, and termination of pregnancy should be recommended if the findings are female or if the genitalia are abnormally developed. Issues often involved in the treatment of TFS: 1. Timing of gonadal debulking There is a consensus on removing the gonads to avoid the occurrence of gonadal malignancies, but the timing of surgery is still controversial. Hannema et al [19] reported that the malignancy rate of prepubertal testes is very small and about 8% after puberty, and the rate of testicular malignancy tends to increase with age; Fallat et al [20] reported that incomplete Fallat et al [20] reported a relatively high rate of testicular malignancy in patients with incomplete forms. The testosterone secreted by the testes can be converted into estrogen, which can promote height growth and the development of female secondary sexual characteristics during puberty. excision should be performed in early adolescence is more appropriate. 2. Guidance on gender orientation The determination of human gender can be divided into six aspects: chromosomal gender, gonadal gender, internal and external genital gender, sex hormone gender, social gender and psychological gender. In normal males or females, these six aspects of gender performance are consistent. In people with abnormal sexual differentiation, there can be multiple inconsistencies and conflicts between these 6 gender expressions. The majority of patients with the complete type have well-developed female external genitalia and are often raised as females; therefore, a female gender orientation is usually recommended. Incomplete patients, on the other hand, because of the unpredictable developmental trend of external genitalia and the change of gender of upbringing may lead to serious psychological abnormalities in the future, therefore, the choice of gender orientation for this type of patients should be treated with particular care. After gonadectomy, estrogen replacement therapy should be given to maintain female secondary sexual characteristics, improve vaginal function and prevent osteoporosis. It has been reported that orchiectomy can lead to a decrease in bone mineral density, and even after postoperative supplementation with regular doses of estrogen, some patients still have a decrease in bone mineral density. Estrogen has the effect of promoting epiphyseal healing, and supplementation should be started in small doses and gradually increased when puberty develops to avoid premature closure of the epiphysis and resulting in short height. In addition, calcium and vitamin D supplements are recommended. 4. Vulvar and vaginal plastic surgery In complete patients, the depth of the vagina is often shallower than normal and the width is narrower than normal, so vaginal dilatation can be performed to increase the depth and width of the vagina. Incomplete patients have different degrees of vulvar deformity and need to undergo plastic surgery. The clitoris is rich in vascular nerves and plays an important role in sexual life. Clitoral reduction and repositioning can preserve the vascular nerves of the clitoris so that the clitoris retains good function. If the vagina is short, vaginal dilatation can be performed. If it fails, vaginoplasty can be performed six months before marriage, and at home and abroad, ileum, sigmoid colon, free flap and peritoneum are mainly used for vaginoplasty. 5, other parts of the plastic In addition to the patient’s vulva and vagina for the corresponding plastic surgery, but also according to the specific requirements of patients, facial, chest and other parts of the plastic surgery, so that patients from the appearance of their choice of gender orientation to maintain harmony.