Congenital ovarian hypoplasia

Introduction to congenital ovarian hypoplasia Congenital ovarian hypoplasia was first described by Turner in 1938. The clinical features of the genitalia are short stature, neck and female genitalia. Later, they are also known as Turner syndrome (Turnerssyndrome). In the form of a cord, the chromosome lacks an X, which was previously referred to as congenital gonadal dysplasia. After the discovery of no Y chromosome, the gonads developed into the ovary, it is also known as congenital ovarian hypoplasia. Still known as Turner syndrome, it is one of the most common sexual dysplasias. basic knowledge The proportion of sickness: 0.01% Susceptible people: women Mode of infection: non-infectious Complications: amenorrhea

Congenital ovarian hypoplasia

(1) Causes of the disease

The majority of the single X chromosome is from the mother, so the lost X chromosome may be caused by the separation of the spermatogonial chromosome of the father. Under certain conditions, the number of chromosomes in the cell may change quantitatively or structurally. The change is called chromosomal aberration. Morgan used the term chromosomal mutation. Some people think that these two terms refer to changes in chromosome structure. To avoid confusion, Ford advocates the collective change of chromosome number and structure as chromosomal abnormality, using chromosomal aberrations (or Mutations are understood in a broad sense, meaning chromosomal abnormalities.

It is known that a variety of factors can cause chromosomal aberrations. It can also be said that most of the mutagenic factors can cause chromosomal aberrations. At present, these reasons are only a general understanding and further research is needed.

Physical factors (15%):

After the Second World War, with the advent of the "Atomic Age", more and more atomic energy was used in human activities. In the development of scientific research, medicine, industry and agriculture, atomic energy has become an indispensable means. Experiments and the exploration of human space into space make ionizing radiation an important factor affecting all human beings and the entire organic world. The radiation environment in which humans are exposed includes natural and artificial radiation. Natural radiation includes cosmic radiation, radiation from the earth and radiation from radioactive substances in the human body. Artificial radiation includes medical and occupational exposures. Ionizing radiation is attracting attention because it causes chromosome segregation. Experiments have shown that comparing the eggs in the middle of MII with irradiated mice and the untreated irradiated eggs, it is found that the separation is not significantly increased in the irradiated group. Especially in older mice, human lymphocytes were irradiated or grown in irradiated serum. It was found that the trisomy frequency of the experimental group was higher than that of the irradiated group, and caused diploid chromosomal translocation, deletion, etc. Chromosomal aberrations have also been reported, and mothers exposed to ionizing radiation have a significantly increased risk of developing children with Down syndrome.

Chemical factors (15%):

People are exposed to a variety of chemicals in their daily lives, some are natural products, some are synthetic, they can enter the body through diet, breathing or skin contact, in addition, many chemical drugs, poisons, anti-metabolites can be Causes chromosomal aberrations, and other alkylating agents such as nitrogen mustard, ethylene oxide, etc. can also cause chromosomal aberrations.

Biological factors (20%):

When cells in culture are treated with viruses, they often cause multiple types of chromosomal aberrations, including rupture, pulverization, and interchange, to convert diploid cells into non-diploids by transforming viral infections; Another special phenomenon has emerged: the cell population in culture has a limited life span, and once it is transformed, it can be cultured indefinitely. Mycoplasma can cause chromosome changes, so when using cultured cells for cytogenesis You should be alert to the infection of mycoplasma when you are diagnosed. Epidemiological evidence of chromosomal damage in viruses suggests that infective mononucleosis, mumps, rubella, chickenpox, chronic active hepatitis, and other patients who cannot make a specific diagnosis are usually involved in viral infections. In these individual lymphocyte cultures, different types of chromosomal aberrations are often seen, and individuals who are attenuated against yellow fever against yellow fever also exhibit significant chromosome pre-injury in their lymphocyte culture.

Mother age effect (15%):

At the age of 6-7 months, all the oogonia cells have developed into primary oocytes, and enter the nuclear network from the first stage of meiosis. At this time, the chromosomes are loosely stretched again, just like the interphase nucleus. This state may be related to synthetic egg yolk until ovulation is maintained. During puberty, due to the periodic stimulation of follicle stimulating hormone (FSH), oocytes complete only the first polar body, secondary oocyte per month. Excreted from the ovary, enters the fallopian tube, and undergoes a second meiosis in the tube to reach the middle stage of division. At this time, if fertilized, the egg will complete the second meiosis, become a mature egg, combine with sperm to form a zygote, and start a new one. From the development of the individual to the childbirth, it can be seen from the above process that when the woman is born, she has all the eggs. From the time of puberty, she can only discharge one from the existing eggs every month, and discharge a few hundred eggs in a lifetime, which also suggests that the age of women The larger the age, the greater the age of the discharged eggs. As the mother age grows, many aging changes may occur in the egg under the influence of many factors inside and outside the mother. The interactions between the same pair of chromosomes in the mature division and the actions in the late stage of division contribute to the non-segregation between chromosomes.

Genetic factors (10%):

Chromosomal abnormalities can be expressed in a familial tendency, suggesting that chromosomal aberrations are related to heredity. Humans may have genes that tend not to be isolated, and other organisms have similar genes. It is reported that the same family has the same or different types of non- The patients with euploidy exist. In addition, parents with chromosomal abnormalities are transmitted to the next generation in different ways. The most obvious example is the carrier of some balanced translocations, which can cause chromosomal abnormalities or normal offspring, which in turn involves D, Group G chromosomes are more common because they are proximal centromere chromosomes, which form a satellite association during mitosis, which may be one of the causes of chromosome segregation.

Autoimmune disease (10%):

Autoimmune diseases appear to play a role in chromosome segregation, such as a strong correlation between increased thyroid primary autoimmune antibodies and familial chromosomal abnormalities.

(two) pathogenesis

Each normal gamete of a diploid organism, that is, all chromosomes contained in a sperm or egg, is called a genome. For example, the genome of a normal human gamete contains 22 +X or 22+Y, called haploid (haploid). , n), the fertilized egg is composed of a sperm containing a genome and an egg containing a genome. Therefore, the individual developed by the fertilized egg has two genomes, called diploid. 2n).

1. Quantitative aberration: If the increase or decrease in the number of normal diploid chromosomes or the entire chromosome is called chromosome number aberration, including euploid and aneuploid.

The number of haplotypes in the euploidy of congenital ovarian hypoplasia.

Aneuploidy: In the diploid, the increase or decrease of individual chromosomes or their segments, including haplotypes and multi-body types.

The karyotype is 45, X's gonadal dysplasia (Turner syndrome) is the most typical example of haplotypes in humans. The haplotype is less than diploid, so it is also called subdiploid, due to monomer The lack of a chromosome in the cell of the individual causes a serious loss of the gene. Therefore, even in the autosome, even the smaller haplotypes of chromosomes 21 and 22 are difficult to survive. 45, X karmic cases may survive. However, most fetuses (about 98%) are aborted during embryonic period. Although survivors have a female phenotype, due to the lack of an X chromosome, the female gonads cannot develop normally, most of them cannot form germ cells, and the external genitalia are not developed. And the lack of secondary sexual characteristics, in addition, the patient still has short stature, neck brace, elbow valgus and other deformities.

2. The formation mechanism of aneuploidy: Most of the causes of aneuploidy are caused by the loss of chromosomes during cell division.

Chromosomes are not separated: in the late stage of cell division, if a pair of homologous chromosomes or two sister chromosome monomers do not move to the poles on average, but enter into a daughter cell nucleus at the same time, the resulting two daughters are formed after cell division. In cells, one will form a hyperdiploid due to the increase in the number of chromosomes, and one will form a subdiploid due to the decrease in the number of chromosomes. This process is called chromosome separation, and chromosome separation does not occur when the gametes are formed. During the process of division, it is said that meiosis does not separate, and it can also occur during the mitosis of somatic cells in the early or late cleavage of fertilized eggs, and mitosis is not separated.

(1) Meiosis does not separate: Meiosis occurs during the maturation phase of gamete formation, including two divisions. See Figure 1. In the first or second meiosis, chromosome segregation can occur, if chromosome Non-separation occurs at the first meiosis, and contains primary chromosomes of two-fold chromosomes (2n=46), forming two secondary spermatocytes with 24 dyads and 22 dyads. After the second meiosis, 2 of the 4 sperm cells will have 24 chromosomes (n+1), and 2 cells will have 22 chromosomes (n-1). After fertilization of the egg of the chromosome, an ultradiploid (2n 1) having 47 chromosomes and a subdiploid (2n-1) having 45 chromosomes will be formed.

When the first meiosis is normal, two secondary spermatocytes with 23 dyads can be formed. If one of the second meiosis occurs, the chromosome does not separate, then one or two points. The two chromosomes formed by the body cannot be divided into two cells on the average, but enter one cell at the same time. The sperm cells will have 24 chromosomes; the other sperm cell has only 22 chromosomes because it does not. Chromosomes, when fertilized with normal eggs containing 23 chromosomes, there will be 1/2 as normal diploid, 1/4 as hyperdiploid (2n 1), and 1/4 as subdiploid (2n Individuals of -1) [Fig. 2 (3)], it is now known that chromosome segregation during meiosis occurs mostly in the first meiosis, and that after the fertilized cells are fertilized, there are many subdiploid individuals. Can not survive, so generally can only produce three-body offspring, this parent is a normal diploid, only in the formation of germ cells, due to the trisomy produced by the meiotic chromosome is not separated, in the cytogenetics called primary non-separation .

If one of the parents is a three-body type (such as mother, 47, XX, 21), at the time of meiosis, there are three chromosomes 21 in the oocyte, one to one pole, and the other two will be assigned simultaneously. The other pole (not isolated), the former forms an egg cell with a normal chromosome number (n), and the latter will form an egg cell of chromosome 21 (n 1). After fertilization with normal sperm, the former can develop into Normal diploid individuals, the latter is type 3: 47, XY 21 or 47, XX 21, the germ cells of the trisomy parental family do not separate during meiosis, said secondary non-separation, sex Trisomy chromosomes (such as XXY and XXX) are also reported by three children. Only 2 cases of XYY male fertility XYY boys may not be able to survive due to YY sperm, so this phenomenon rarely occurs.

(2) Somatic cells do not separate: In the earliest stage of embryo development - cell division in the cleavage stage of the fertilized egg, if the sister chromosome monomer of a certain chromosome does not separate, the chimera will be produced.

(3) Chromosome loss: when the chromosome is lost or lost during the mitosis of the cell, during the middle to late stages, the two sister chromosomes will move to the poles respectively by the pulling of the spindle, if the centromere of a certain chromosome is not related to the spindle When connected, they cannot be pulled to a certain pole and participate in the formation of new nuclei; or when a certain chromosome monomer moves toward a pole, it causes slowness of action for some reason, late delay, and cannot participate in the formation of new nuclei. It stays in the cytoplasm and finally decomposes and disappears. As a result, a cell is about to lose one chromosome to form a subdiploid.

Chromosomal loss is also a form of chimerism. In particular, only the XO/XY cell lines are seen clinically, and chimeric cases without trisomy cell lines can be explained by chromosome loss.

Congenital ovarian hypoplasia prevention

prevention:

Congenital ovarian hypoplasia is a sex chromosome disease, the cause is still unclear, refer to the relevant preventive measures of genetic diseases:

1. Prohibit close relatives from getting married.

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

3. The detection of the carrier: determine whether it is a genetic disease by means of group census, family survey and pedigree analysis, laboratory examination, etc., 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, pathogenesis, genetic pattern, treatment and prognosis of the disease, 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 disease of children should be distinguished by intrauterine environmental factors, labor injury and hypoxic ischemic disease or genetic factors. Therefore, it is necessary to understand the history of the child's 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 clinical manifestations, combined with relevant laboratory tests, make a clear diagnosis. If the chromosomal abnormal disease 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: 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 line examination (after 5 months of pregnancy) is beneficial for the diagnosis of fetal skeletal deformities;

5 Determination of sex chromatin in villus cells (40 to 70 days of conception), predicting fetal gender to help diagnose X-linked genetic diseases;

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.

Do a good job of preventing the cause, prevent chromosomal aberrations, and treat the child early to prevent future complications.

Congenital ovarian dysplasia complications Complications amenorrhea

Height, weight behind, can be associated with heart, kidney deformity and so on.

Congenital ovarian hypoplasia symptoms Common symptoms Uterine abortion anti-ovarian antibody positive amenorrhea orbital ptosis neck short hairline low lymphadenopathy

The clinical features are short stature, genital and secondary sexual characteristics are not developed, and a group of physical development abnormalities, the height is generally less than 150cm, female vulva, developmental naive, vaginal, small or absent uterus, physical characteristics of sputum, eyelids Drooping, low ear size, high zygomatic arch, low posterior hairline, short and wide neck, neck brace, chest barrel or shield, large nipple spacing, no breast and nipple development, elbow eversion, 4th or 5 metacarpal or humerus short, palmprint clearance, lower limb lymphedema, renal malformation, aortic arch stenosis, etc. These characteristics are not necessarily in every patient, mental development is different, completely normal, poor intelligence, longevity and Normal people are the same, the mother's age seems to be unrelated to this developmental abnormality, LH and FSH increase significantly from 10 to 11 years old, and the increase of FSH is greater than the increase of LH. Peking Union Medical College Hospital uses single photon (SPA) to measure Turner synthesis. 40 cases were enrolled, 13 of them also used QCT to measure bone density. It was found that the bone mineral density of Turner patients was significantly lower than that of normal women of the same age.

In addition to 45, X, Turner syndrome can have a variety of chimeras, such as 45, X / 46, XX, 45, X / 47, XXX, or 45, X / 46, XX / 47, XXX, etc., clinical According to which cell line in the chimera is the majority, the normal sex chromosome is the majority, the abnormal signs are less, and if the abnormal chromosome is the majority, the typical abnormal signs are more.

Turner syndrome can also be due to abnormalities in sex chromosome structure, such as the arm Xi (Xq) of the long arm of the X chromosome, the arm Xi (Xp) of the short arm, the missing XXq-, XXp- of the long arm or short arm, forming a circular Xxr (Figure 8 Or translocation, clinical manifestations are related to the number of missing, the missing may still have residual follicles and may have menstrual cramps, but amenorrhea several years later.

The genital genitalia can be seen in the laparotomy, but the gonads are small, and the gonads are strip-shaped, 2~3cm long and 0.5cm wide. In the ovary-like part, the thin cortex, medulla and door are observed under the microscope. The cortex is a typical ovarian stroma, the cell is long wave-shaped, and there are portal cells and ovarian nets in the portal. At the 45th week before the 12th week of pregnancy, the X embryo has a normal number of primordial follicles, and the number is reduced when the fetus is larger. Almost no birth, clinically encountered individual patients can be pregnant, but short reproductive life, premature ovarian failure, may be related to the slower consumption of eggs in these patients during embryonic period, so you can understand which patients with Turner syndrome have follicles and can give birth very much Importantly, the chromosomes of pregnant cases were analyzed as 45, X/46, XX chimerism. When the 46, XX cell line was dominant, the ovary could develop and maintain normal function. 45, X individuals were 8% and 45, X /46, 21% of XX individuals can have normal puberty development and menstruation, ovarian no follicles and lack of function when pituitary gonadotropin FSF and LH increase, a small number of Turner syndrome patients FSH and LH do not increase but in the normal range ,through After laparoscopic examination, these patients were found to have small ovaries. The biopsy showed follicles in the ovary. If the patients with Turner syndrome were pregnant, there were more abortions. 45, X fertilized eggs could not develop and many abortions occurred, accounting for miscarriage. 5.5% to 7.5%.

In 1971, Andrews proposed that the deletion or chimerism of the sex chromosome not only affects the development of the gonads and reproductive tract, but also affects the abnormal characteristics of the Turner syndrome. In the absence of an X, in addition to the non-development of the gonads, there are various bodies of Turner syndrome. Abnormal performance, X short arm loss, also has the characteristics of Turner syndrome, long arm loss only ligament gland without body abnormalities. In 1972, Neu et al also considered Turner syndrome short stature related to short arm loss, sex chromosome X , XXp- or XXqi are short, when the sex chromosome X loses the long arm, such as XXq- or XXpi only amenorrhea and cord-like gonads, no body short and other abnormalities of Turner syndrome, so the ovarian and egg differentiation is considered Two sites are needed on the sex chromosome, one on the long arm and the other on the short arm. Losing any point will cause hypogonadal hypoplasia. The abnormal development of height and gonads is related to the long arm and the short arm. Normal The long arm and the short arm are indispensable, but the short arm plays a decisive role, as does the gonad, but the long arm plays a major role.

Congenital ovarian hypoplasia

Hormone level testing, chromosome testing, bone density testing. Colposcopy, laparoscopy.

Diagnosis and diagnosis of congenital ovarian hypoplasia

In addition to the clinical features, the karyotype is first examined, the chromosomes are 45, X, and a sufficient number of cells are needed to determine whether there is a chimera. If the structure is abnormal, the deletion or translocation part needs to be understood by the banding technique. Chromosome.

Another clinical manifestation similar to Turner syndrome, short stature, genital non-development and various body abnormalities, but the chromosome is 46, XX, formerly known as XX Turner, also known as Ullrich-Noonan syndrome, both de-sex Extrachromosomal, the main difference is that Ullrich-Noonan syndrome can have normal sexual development and conception during adolescence, and is autosomal dominant.

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