male pseudohermaphroditism
Introduction
Introduction to male and female bisexual malformations The pseudo-sexual malformation is the heterogeneity of genetic sex, gonad sex and phenotypic gender, that is, the sex of the gonad is consistent with the genetic gender, while the development of the reproductive duct and urogenital sinus has the opposite sex or the characteristics of both sexes, with genetic gender. Based on the sex of the gonads, the pseudohermaphroditism can be further divided into female pseudohermaphroditism and male pseudohermaphroditism. The basic feature of male and female amphoteric malformation is 46, XY. If the gonad can be found, it is definitely the testicle, but the vulva is incomplete, ambiguous, or completely feminine. Because the process of normal masculinization in the fetus is very complicated, There are many types of male and female malformations. basic knowledge The proportion of illness: 0.001% Susceptible people: male Mode of infection: non-infectious Complications: small penis hypospadias cryptorchidism
Cause
The cause of male and female malformation
(1) Causes of the disease
The main causes of male sex and hermaphroditism are: First, the androgen deficiency is not complete, its synthetic testosterone is normal, but the androgen plays an abnormal role, and the second is the testicular hormone synthesis defect. When the mesenchymal cell differentiation disorder or the enzyme has genetic defects, it may lead to 46, XY fetal middle kidney tube male reproductive duct and external genital differentiation is not complete, resulting in male pseudohermaphroditism, the third is Y chromosome structural abnormalities or gene mutations, or other chromosomal abnormalities leading to gonadal dysplasia.
(two) pathogenesis
The mechanism of male and female malformation is related to the following androgenic action defects:
1 reduced androgen production, such as 3-HSD, 17-HSD and 5-reductase deficiency;
2 androgen receptor (AR) gene mutation, causing a decrease in AR number and dysfunction;
35 reductase deficiency, can not convert testosterone into dihydrotestosterone (DHT); 4 target cell intracellular androgen metabolism abnormalities, etc., AR mutation is the main cause of feminization of complete and incomplete testis.
The human androgen receptor (AR) gene is located at Xq11~12, and more than 200 AR gene mutations have been found, among which the single-base mutation accounts for more than 90%. The AR gene mutation causes AR binding loss and DNA structure abnormality, including completeness. Sex gene deletion, exon deletion and point mutation encoding the androgen binding region or DNA binding region.
1. Complete type testicular feminine testicular feminine patients with chromosome sex is 46, XY, often familial onset, family analysis is X-linked recessive genetic disease, near the centromere on the long arm of the X chromosome - androgen receptor The gene is mutated, and the target cell lacks a specific protein that binds to androgen. Although there is a biologically active androgen, it does not bind to it and loses its reactivity. The hypothalamus is also insensitive to androgen and loses a negative feedback mechanism. The pituitary gland secretes a large amount of gonadotropin to stimulate stromal cell proliferation. It has been confirmed that the androgen receptor gene is located at Xq11~12, the length is greater than 90kb, and there are 8 exons. Exon 1 occupies the entire amino terminus and has the function of stimulating transcription. Most of the testicular feminization patients are genetic point mutations or base pair deletions, leading to defects in androgen receptors, resulting in male genital transformation is blocked.
These patients are caused by the lack of androgen receptor in the target tissue, so they are not sensitive to testosterone. They are the most common type of male sex and hermaphroditism. The incidence rate is about 1:12 million in newborns, with a family history. The testicles under the microscope are like the cryptorchidism before development, the seminiferous tubules become thinner, the tube is filled with supporting cells and immature spermatogenic cells, spermatogenesis is impaired, but the interstitial cells are still proliferating, and the testes are prone to malignant transformation.
2. Incomplete type testicular feminization, also known as 5-reductase deficiency, genetic studies confirmed that the patient's karyotype is 46, XY, parental phenotype is normal, the incidence increases with blood marriage, family analysis can be traced back to common The ancestors are sick, both sexes have abnormal defects in the enzymes, and both sexes have phenotypically normal gene carriers, supporting autosomal recessive inheritance.
It is known that testosterone plays a role in the conversion of dihydrotestosterone by the action of 5-reductase in androgen-sensitive target tissues; testosterone and dihydrotestosterone are indispensable in the differentiation of male genitals into males, if male In the early stage of development, the fetus lacks 5-reductase, and the dihydrotestosterone deficiency in the target tissue causes abnormal development of the external genitalia, which is often difficult for women or men and women.
According to the results of 5-reductase activity assay, the disease can be divided into two types: enzyme deficiency and enzyme instability. The results of genetic analysis indicate that the lack of enzyme activity is caused by mutation and deletion of the gene, or the enzyme cannot bind to testosterone. , or affect the function of the enzyme; or the mutation outside the enzyme encoding gene affects the expression of the gene.
Prevention
Male and female malformation prevention
The cause of this disease is not clear, early detection, early diagnosis, early treatment is of great significance for the prevention of this disease. Regular examination should be done during pregnancy. If the child has a tendency to develop abnormalities, chromosome screening should be done in time, and abortion should be performed in time to avoid the birth of the diseased child. For children with bothergic malformations, the gender is determined before the age of 2, because the children after 2 years of age have obtained corresponding psychological developments for their gender, such as changing their gender, it may cause future psychological abnormalities. Therefore, the gender of children with gender deformity over 2 years old should be determined according to the shape and gender of the external genitalia. According to the determined gender, the corresponding shaping surgery is selected, and the corresponding sex hormone therapy is given when necessary to promote the development of gender-consistent secondary sexual characteristics.
Complication
Male and female malformation complications Complications small penis hypospadias cryptorchidism
Small penis: small penis (micropenis) means that the appearance of the penis is normal, the ratio of length to diameter is normal, but the length of the penis is less than 2.5 standard deviations above the average length of the normal penis. The length of the penis refers to the straightening of the penis head as much as possible, which is equivalent to the distance from the top of the penis to the pubic symphysis when the penis is fully erect. Adults generally have a penis relaxation length of less than 3 cm for a small penis.
Hypospadias: The urethral ectopic opening in the ventral side of the urethra is called hypospadias. The hypospadias opening can occur anywhere from the perineum to the penis head. The distal end of the external urethra, the urethra and surrounding tissues are underdeveloped, and the formation of a fiber cord involves the penis, causing the penis to bend to the ventral side. Congenital penile curvature is not all of the hypospadias, but the hypospadias have different degrees of penile curvature.
Cryptorchidism: Cryptorchidism refers to any place where the unilateral or bilateral testes of a baby boy have not fallen to the scrotum and remain in their normal decline. That is to say, there are no testicles in the scrotum or testicles on only one side.
Symptom
Male and female gender deformity symptoms Common symptoms Mild malformation masculine amenorrhea breast hypertrophy cryptorchidism penis short
1. The external genitalia of the fully-type testicular feminized patients is completely the same as the normal female, the clitoris is not hypertrophy, but the vagina is relatively shallow, blind, no cervix, no uterus and fallopian tubes in the abdominal cavity, primary amenorrhea, testis on both sides The position can be in the abdominal cavity, in the groin and the labia majora, the most common in the groin (78%), the breasts on both sides are hypertrophied, but the glandular tissue is less, the nipple is poorly developed, and the body shape is also female. One feature is that the patient has no mane and pubic hair (no hairy woman).
2. Incomplete testicular feminization patients reproductive tract, gonads, plasma sex hormones and gonadotropins, karyotype, genetic pattern, etc. are the same as complete testicular feminization, but the vulva has different degrees of masculinization, accompanied by pubic hair And mane growth, because the amount or quality of the target tissue androgen receptor is lower than the normal level rather than a complete lack, so there are varying degrees of masculinity.
(1) Lubs syndrome: The renal tube is partially developed in the patient, with sexual hair, male body type, combined with post-fusion, and the external genitalia tends to be female.
(2) Gilbert-Dreyfus syndrome: The patient is male, with a small penis, accompanied by hypospadias, partial renal tube development, breast hypertrophy, and masculine degree.
(3) Reifenstein syndrome: male vulva, short penis, varying degrees of hypospadias, scrotal bifurcation, developmental breast hypertrophy, sexual hair, infertility.
(4) Rosewater syndrome: male genital and genital tube, breast hypertrophy during development, fat distribution is female, sexual hair, infertility.
(5) false vaginal perineal scrotum type hypospadias: in this type of patients due to 5-alpha reductase deficiency, testosterone can not be converted to 5- dihydrotestosterone, the result is that the penis is like a clitoris, the urethra is in the perineum, there is a shallow The vagina, the middle kidney tube differentiates like a normal male, that is, there are seminal vesicles, vas deferens, epididymis, ejaculation tube opening in the genital sinus, testis in the groin or bifurcation scrotum, mature sperm and various sperm cells in the semen of adult patients In the developmental stage, male secondary sexual characteristics: muscle development, low voice, breast development, penis enlargement, erection and ejaculation, hormone test showed blood testosterone value is the same as normal male, and 5-alpha dihydrotestosterone value Decreased, 5--dihydrotestosterone is almost undetectable in tissues such as patient foreskin, corpus cavernosum, etc., indicating that 5-alpha reductase is absent in these tissues, resulting in urinary sinus and genital dysplasia not fully developing in the male direction, according to Analysis of the patient's genealogy, the patient's genetic pattern may be autosomal recessive.
Examine
Examination of male and female bisexual malformations
1. Complete testicular feminine hormone test showed that serum FSH and LH were normal or slightly elevated, testosterone concentration was equivalent to male adult level, estradiol concentration was higher than male adult level, and testicular biopsy showed smaller testicular volume. The leukorrhage is smooth, the vas deferens, the epididymis, the seminiferous tubules are underdeveloped, the wall is degenerated, there are spermatogonial cells, but no sperm is produced, and the interstitial cells are poorly proliferated, sparsely distributed around the seminiferous tubules.
2. Incomplete testicular feminization endocrine examination Testosterone levels in puberty patients are similar to normal men, mainly due to low dihydrotestosterone levels, increased ratio of testosterone to dihydrotestosterone, plasma luteinizing hormone (LH) Mild rise, urinary 17-hydroxycorticosteroid (17-HS) and 17-ketocorticosteroid (17-KS) were normal.
Diagnosis
Diagnosis and diagnosis of male and female hermaphroditism
diagnosis
Complete testicular feminization can be based on karyotype 46, XY, female phenotype, uterine absent, inguinal hernia, no pubic hair, cryptorchidism and male serum testosterone determination can determine the full-type testicular feminization diagnosis.
Incomplete testicular feminization is basically the same as full-type testicular feminization, the difference is that some masculine symptoms and signs appear.
Differential diagnosis
Related diseases that should be differentially diagnosed in testicular feminization syndrome include:
1. Secondary renal tubular hypoplasia syndrome (Mayer-Rokitansky-Kuster-Hauser syndrome, MRH syndrome) is congenital absence of vaginal malformation, MRH syndrome karyotype is 46, XX, bilateral gonads are ovary, no Vagina, but with pubic hair and mane development, the internal genitalia is female, serum estrogen concentration is normal.
2. The karyotype of true amphoteric malformation is 46, XX or 46, XY or chimeric, bilateral gonads are testis / ovary / egg test, genital development of both sexes, vulvar deformity, phenotype is female or male or deformed.
3. Klinefelter syndrome is congenital testicular hypoplasia, chromosome karyotype is 47, XXY can be identified.
Children are easily confused with 17-hydroxydehydrogenase deficiency, which is a defect in testosterone biosynthesis. It also has the characteristics of pseudovaginal, perineal, and scrotal hypospadias, but the plasma testosterone is normal and puberty is progressive. Male development can rule out insufficient testosterone production.
