Congenital testicular hypoplasia in children

Introduction to congenital testicular hypoplasia in children Congenital testicular hypoplasia, also known as Klinefetter syndrome (Klinefettersyndrome), is a high incidence of sex chromosome disease. Before the chromosome identification, Klinefelter first reported the disease in 1942. In 1956, Bradbury et al showed that the patient was intracellularly present. Female X chromatin, Jacobs and Strong first discovered in 1959 that the patient's karyotype was 47,XXY. Due to abnormal sex chromosomes, testicular hypoplasia, infertility, and low intelligence. basic knowledge Sickness ratio: 0.0004% Susceptible people: children Mode of infection: non-infectious complication:

Pediatric congenital testicular hypoplasia

(1) Causes of the disease

This disease is a sex chromosome abnormality. Most patients have an X chromosome, so the most common peripheral blood leukocyte karyotype is 47,XXY, or chimera 47,XXY/46,XX or 47,XXY/48,XXXY, There are even more X chromosomes, such as 49, XXXXY, and those with positive oral mucosal X-small examinations account for 93% of the XXY karyotype.

The various karyotypes of this disease are the result of the isolation of the mature chromosomes or the sex chromosomes or sex chromatids that occur in the cleavage of the fertilized eggs. From the study of chromosomal gene markers, the egg cells are not separated more than twice as much as the sperm. The above-mentioned sex chromosome malformation has many chances in the pregnancy of the elderly women, which may be due to the aging of the egg cells, the weakening of the longitudinal fissure, or the spindle fascination. There are indications that the number of X chromosomes in the disease is more. The glassy degeneration, the more serious the interstitial fibrosis, the more the mental development is involved, the mechanism is unknown. Some scholars have deduced that the X chromosome gene has an adverse effect on testicular development. Therefore, the main pathological feature of this disease is the dysplasia of the curved tube. Small testicles, can not produce sperm or sperm is very rare, so no birth, interstitial cells are adenoma-like clusters, the lipid content and secretory granules in the cells are reduced, and some cases have abnormal EEG, suggesting a slight Organic brain damage, this line of primary or secondary to endocrine dysfunction is inconclusive.

(two) pathogenesis

Congenital testicular hypoplasia is a congenital testicular dysplasia or non-developmental disease, patients often see infertility due to infertility or physical examination of the genital tract, and then confirmed by chromosome examination.

The common feature of different types of the disease is that the sex chromosome has one or more X chromosomes than the normal XY. The excess X chromosome has adverse effects on the testis and signs, especially on the signs. The more X chromosomes, The more obvious the degree of testicular dysplasia, the more severe the symptoms, the worse the mental development, and the more often the other malformations. Because the Y chromosome has a testicular determinant gene (TDF), the patient has a Y chromosome, so the patient's phenotype is male, but the patient's phenotype is male. Exceeding normal X chromosomes leads to varying degrees of feminization.

Congenital testicular hypoplasia has more karyotypes. Of the 62 cases reported by Wang Defen in China in 1987, 47,XXY accounted for 71.0%, 47,XXY/46,XY chimera accounted for 24.2%, 48,XXXY and 48, XXYY is about 3.2% and 1.6% each. The formation of these karyotypes is due to cell maturation and division, or the segregation of sex chromosomes or sex chromatids in the cleavage of eggs, chromosomal gene marker studies suggest that egg cells Do not separate more than 2 times of sperm, sex chromosome aberrations, the chances of pregnancy in older pregnant women, may be due to the aging of egg cells, the weakening of the longitudinal fissure or the spindle fascination, leading to the formation of the parental germ cells There is no segregation of sex chromosomes. Some analysis shows that 60% of patients are due to the absence of maternal chromosome separation, 40% are due to the separation of the father's chromosome, and about 83% of the chromosomes are not separated during the mature division. The first meiosis, 17% may occur in the second meiosis.

Due to the increase of X chromosome, the testis is not developed, the penis is short, the plasma testosterone is decreased, FSH and LH are increased; the androgen secretion is insufficient, and the increase of FSH may be due to the support of cell damage, the decrease of secreted statin, and the low testosterone level. It indicates that the testosterone function of testicular interstitial cells in this patient is reduced, which will inevitably increase the LH compensatory. By electron microscopy, there are abnormal mitochondria and endoplasmic reticulum in the interstitial cells of the testis, which may interfere with testosterone organisms. The material basis of synthetic barriers.

Congenital testicular hypoplasia prevention in children

Chromosomal malformations of congenital testicular hypoplasia, in the elderly women with more chances in pregnancy, can refer to the relevant preventive measures of genetic diseases:

1. Prohibit close relatives from marrying and avoiding older pregnancies.

2. Premarital examination to discover genetic diseases or other diseases that should not be married.

3. The detection of the carrier is determined by group census, family survey and pedigree analysis, laboratory examination and other means to determine whether it is a genetic disease, and determine the genetic mode.

4. Genetic counseling

(1) Genetic counseling:

1 Patients diagnosed with hereditary diseases and their relatives.

2 consecutive families with unexplained diseases.

3 congenital primary intelligence is low, suspected of genetic related.

4 balance translocation chromosomes or carriers of disease-causing genes.

5 Women with unexplained recurrent miscarriage.

6 sexual dysplasia.

7 have a family history of hereditary diseases and intend to marry and give birth.

(2) The main objectives of genetic counseling:

1 pair of patients themselves:

A. Determine the diagnosis of the disease, the cause of the disease, the genetic pattern, the treatment and the prognosis, and further analyze whether the patient's disease-causing gene or chromosomal abnormality is caused by a new mutation or a previous generation.

B. Relieve the physical and mental pain and anxiety of the patient.

C. Give early attention to patients who are not ill, and give necessary treatment.

2 For both parents and relatives:

A. Detection of carriers and recessive cases in the family.

B. Determine the risk of developing a member of the family.

C. Help couples who are at risk of having children with genetic diseases to help them scientifically and consider birth plans in accordance with family planning regulations.

(3) Genetic estimation of pediatric diseases:

1 The difference between the diseases of children is the intrauterine environmental factors, the birth injury and the pathogenesis of hypoxia-ischemia or genetic factors, so it is necessary to understand the history of the parents (such as taking drugs, the nature of work, etc.), The mother's pregnancy history, the birth history of the child, etc., in addition to various physical and chemical, biological factors on the embryo and the fetus.

2 Asking about family history and analyzing genealogy is one of the basic methods of genetic counseling.

3 According to the clinical manifestations, combined with the relevant laboratory tests, make a clear diagnosis, such as chromosomal abnormalities must be combined with karyotype analysis can be determined.

(4) Identify the genetic characteristics of each genetic disease: it is of great significance for guiding birth.

5. Prenatal diagnosis of prenatal diagnosis or intrauterine diagnosis is an important measure of preventive eugenics. The prenatal diagnostic techniques used are:

1 amniocytes culture and related biochemical examination (amniotic puncturing time is 16 to 20 weeks of pregnancy is appropriate).

2 pregnant women blood and amniotic fluid alpha fetoprotein determination.

3 ultrasound imaging (applicable in about 4 months of pregnancy).

4X-ray examination (after 5 months of pregnancy) is beneficial for the diagnosis of fetal skeletal deformities.

The sex chromatin of 5 villous cells was measured (40 to 70 days after conception), and the sex of the fetus was predicted to help diagnose the X-linked genetic disease.

6 application gene linkage analysis.

7 fetal mirror examination.

Through the application of the above technology, the birth of a fetus with severe genetic diseases and congenital malformations is prevented.

Congenital testicular dysplasia complications in children Complication

1, androgen deficiency: no testicular body type, normal or high body, longer limbs, normal or short penis, low sexual function, about 97% of patients with infertility, osteoporosis and decreased muscle strength.

2, up to 13% of patients with varicose veins, thrombosis, chronic leg ulcers, may be due to a decrease in fibrinolysis caused by androgen deficiency, rather than vascular anatomical changes.

3. Learning, language, and intellectual barriers.

Congenital testicular hypoplasia in children Common symptoms Testicular hypoplasia vulva is naive type without pubic hair Adolescent body development slow testicular tiny male infertility no beard male breast big learning disorder children behavioral loneliness

The incidence of this disease is quite high, but many patients have no symptoms or discomfort except infertility, so they will not see a doctor, it is difficult to find, the patient's phenotype male, the body is thinner, the body is taller, the finger spacing is greater than the height, the breast is often increased Large, breast feminization accounts for about 40%, in 47,XYY and 48,XXYY karyotype, patients with 2 Y chromosomes have higher body type performance, puberty development is often delayed, due to lack of sperm, generally can not be born (occasionally exceptional ).

Physical examination found that male secondary sexual characteristics were not obvious, no beard, no larynx, fair skin, small testicles, small penis, cryptorchidism or hypospadias, poor pubic hair development.

Patients may be unsociable, awkward, inactive, timid, and lacking a boy's personality. In the standard 47, XXY karyotype, about 25% show moderate mental retardation, manifested as language and learning disabilities, which is in adolescence. There is a lack of obvious symptoms before, and it is difficult to recognize. If a routine karyotype analysis is performed on children with intelligent backwardness or abnormal behavior, early diagnosis can be performed.

Congenital testicular hypoplasia can be diagnosed in cryptorchidism or small testicles in childhood, but most of the symptoms are not serious, lack of characteristic or physical examination negligence is not easy to be valued, generally in puberty, due to testicular development, masculinization Some patients have women with breast development or infertility.

Pediatric congenital testicular hypoplasia

1. Cytogenetic testing

(1) Oral mucosal X chromatin examination: X chromatin is also called X body (Barr body). Under normal circumstances, the number of X bodies is equal to the number of X chromosomes minus 1. Normal males have only one X chromosome. X small body test is negative, and the patient has 2 or more X chromosomes, so one or more X small bodies can be detected in their oral mucosal cells. The examination method is simple, and the smear is mirrored. The results of the test can be used as a preliminary screening test for sex chromosome abnormalities, and cells without cell culture conditions can also be performed, but the correct karyotype analysis cannot be performed.

(2) Karyotype analysis:

1 Analysis of karyotype of peripheral blood lymphocytes: The sex chromosome in normal male somatic cells is XY, the standard chromosome of the disease is XXY, which is a trisomy of sex chromosomes, and 80% of the karyotypes are standard type 47,XXY or standard. Type karyotype, such as 48, XXXY. 48, XXYY. 49, XXXXY. 49, XXXYY, 15% is a chimera type, and the chimera has 47, XXY. 46, XY. 47,XXY. 46, XX. 47,XXY. 46, XY. 45, X. 47,XXY. 46, XY. 46, XX, etc.

2 karyotype analysis of amniotic fluid cells: In order to prevent the birth of children with congenital sex chromosome disease, amniocentesis was performed at the 16th to 20th week of the second trimester, amniocytes were taken, and the karyotype analysis of the fetus was performed after culture, and the abnormal nucleus was found. The timely termination of pregnancy can reduce birth defects.

2. Fluorescence in situ hybridization

In the second trimester of pregnancy, the karyotype analysis of the fetus, whether it is peripheral blood lymphocytes or amniocytes, can be performed after cell culture for karyotype analysis, so it takes time, and fluorescence in situ hybridization detection does not require cell culture, and can directly Hybridization detection of cells during the period shortens the diagnosis time. For prenatal diagnosis, the method has its advantages. It can be directly mixed with villous cells and amniotic fluid cells, and the conclusion can be reached in one day. If there is abnormality, it can be terminated. Pregnancy, the time to end the pregnancy early.

3. Biochemical testing and other tests

Testosterone in patients with serum decreased, feedback inhibition of hypothalamic pituitary decreased, pituitary gonadotropin luteinizing hormone (LH), urinary tropin (FSH) increased, serum testosterone levels were lower than normal; gonadotropin-releasing hormone (LHRH) Excitatory tests showed an increase in FSH response and a normal LH response; testosterone was low in human chorionic gonadotropin (HCG) stimulation test.

There was no sperm production in the semen of the patient, and the pathological examination of the testicular biopsy showed degeneration of the seminiferous tubule and interstitial cell hyperplasia.

Abdominal B-ultrasound, electrocardiogram and X-ray examination to see if there are other abnormalities and abnormalities.

Diagnosis and diagnosis of congenital testicular hypoplasia in children

diagnosis

According to clinical features, patients suspected of congenital testicular hypoplasia can be biochemically examined. If serum FSH, LH is increased, testosterone level is lower than normal, the karyotype analysis of peripheral blood lymphocytes can be performed on the patient to determine the number of X chromosomes. It is the main basis for the diagnosis of congenital testicular hypoplasia, FISH technology is a rapid diagnosis method.

Differential diagnosis

Intrinsic to delay diagnosis of puberty development, congenital testicular hypoplasia in the adolescent blood gonadotropin is significantly elevated, testosterone levels are lower, while puberty development delay is at an undeveloped level, no gonadotropin elevation, such as this After the puberty, the testicular biopsy was performed, and the seminiferous tubules were found to have a glassy change. Although the Leydig cells were increased, the endocrine viability was insufficient.

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