Congenital ovarian hypoplasia in children
Introduction
Introduction to congenital ovarian hypoplasia in children Congenital ovarian hypoplasia, also known as Turner syndrome (Turnerssyndrome), is the most common sex chromosome disease (sexchromosomedisease), and is the only genetic disorder in humans that can survive the birth of a complete chromosome. The main feature of this syndrome is Female appearance, not developed during puberty, primary amenorrhea, short stature, neck brace, elbow valgus, etc., the gonad is fibrous cord-like. basic knowledge The proportion of illness: 0.001% Susceptible people: infants and young children Mode of infection: non-infectious Complications: kidney damage in solid tumors
Cause
Congenital ovarian hypoplasia in children
(1) Causes of the disease
The karyotype of this disease is 45, XO, lacking a sex chromosome. In addition, there are various combinations of chimeras. The highest rate of occurrence of XX/XO in chimeras is rare. Abortion is rare in chromosomes. The symptoms are also mild. It is believed that in XO/XX type, the higher the proportion of XO cells, the lower the percentage of sex chromatin and the more abnormal deformities. On the contrary, when the proportion of XX cells is higher, the percentage of sex chromatin is also higher. High, relatively few malformations occur because meiosis does not separate the sex chromosomes of the egg or sperm, allowing an asexual chromosome to bind to a sperm with an X chromosome, or an egg with an X chromosome The sperm of an asexual chromosome is combined. Most of the fetuses with such abnormalities often have spontaneous abortion, and live births are far less than testicular hypoplasia.
(two) pathogenesis
Congenital ovarian hypoplasia is caused by X-chromosome deletion or structural changes in cells. The genetic basis of X-cell chromosomes is still unclear. The possibility of genetic imprinting has been ruled out. The possible mechanisms are: 1 parental germ cells The meiosis does not occur; the sister chromatid does not separate in the zygote cleavage; 3 the partial loss of the X chromosome during mitosis.
Since one of the two X chromosomes of the female has been inactivated and not transcribed in the early stage of embryonic development, only one X chromosome plays an active role in the development of the human body. From this point of view, the Turner syndrome phenotype is not X. Monomer-induced, may involve some defects of Turner syndrome-related genes that have not yet been clarified. The theoretical basis for this speculation is:
1. Early expression theory Before the embryonic development and X chromosome inactivation, X-linked genes involved in human cell development may have been expressed and expressed in double doses.
2. Incomplete inactivation theory Inactivation of X-linked genes on the X chromosome does not appear to be completely inactivated, and there may be incompletely inactivated regions, since gene expression in this region is a key factor in the clinical phenotype of congenital ovarian hypoplasia. Therefore, it is suggested that the genes related to congenital ovarian hypoplasia are likely to be located in this region. The results of Y chromosome studies indicate that because some patients with congenital ovarian hypoplasia are accompanied by Y-centromere derivatives, it is considered that sex-determining genes and Congenital ovarian hypoplasia-related genes are genetically two completely independent gene control sites. The study also found that some patients have Y chromosome genes (RPS4Y) and X chromosome genes (RPS4X) related to congenital ovarian hypoplasia. Linked, and can encode a 40S protein isoform, suggesting that the linked gene may be a candidate gene for congenital ovarian hypoplasia.
In short, the pathogenesis of congenital ovarian hypoplasia is currently being studied in the direction of molecular genetics.
Prevention
Congenital ovarian hypoplasia prevention in children
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 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 children's diseases is the intrauterine environmental factors, birth injury and hypoxic ischemic disease 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 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.
Complication
Congenital ovarian hypoplasia complications in children Complications kidney damage in solid tumors
Kidney malformation: The kidney can have a variety of deformities. The deformed kidney can cause pressure on other organs. The kidney itself can cause infection, hemorrhage, stones, kidney disease or renal vascular hypertension, and severe renal parenchyma. If it is reduced, kidney failure occurs.
Symptom
Symptoms of congenital ovarian hypoplasia in children Common symptoms Amenorrhea in the amenorrhea or hypoplasia of the hairline Low growth slow vulva is naive type without pubic vulva Childish female secondary sexual characteristics disappeared neck short edema
Typical congenital ovarian hypoplasia patients have height at birth and are underweight. In the neonatal period, there are special symptoms such as excessive folding of the skin behind the neck and edema in the hands and back of the foot. The patient is a female phenotype, growing slowly, and adulthood. Height is about 135 ~ 140cm, in addition to genitals, breasts are not developed, primary amenorrhea and lack of secondary sexual characteristics, there is still a dull face, normal intelligence or slightly lower, about 18% of patients have intelligent backwardness, short neck, 50% have neck sputum, posterior hairline is low, the distance between the two nipples is widened, and the pigmentation of the nipple becomes deeper with age, and there are symptoms such as elbow valgus and skin edema. About 35% of the children have heart malformations. Arterial constriction is more common. Recently, it has been reported that patients with Turner syndrome were examined by echocardiography. 34% of cases were found to have aortic valve type, but no stenosis, and patients may have renal deformity. , 5 metacarpal bones are shorter.
Patients often suffer from growth retardation, adolescent non-sexual development, primary amenorrhea, etc., and their serum FSH, LH have increased in infancy, and estradiol levels are very low.
Examine
Pediatric congenital ovarian hypoplasia
1. Peripheral blood cell karyotype analysis The peripheral blood lymphocyte culture technique and chromosome specimen preparation method can be used for karyotype analysis of chromosomes, and the abnormal karyotypes include:
(1) haplotype: 45, XO is the most common type, accounting for about 60%. Most of the karyotype individuals spontaneously abort in the early pregnancy, and the remaining surviving individuals have typical clinical symptoms.
(2) chimeric type: karyotype is 45, XO/46, XX, accounting for about 25% of the disease, and the individual type of cell type 46, XX is mild, and about 20% of patients may have menstrual cramps Some have fertility. If the patient is mainly 45, XO cells, the phenotype is similar to the haplotype.
(3) X chromosome structural aberration: 46, Xdel (Xq) or 46, Xdel (Xp), that is, one X chromosome long arm or short arm deletion, accompanied by X chromosome translocation.
2. Amniocentesis Chromosome Examination In the second trimester, amniocentesis is performed on high-risk pregnant women. The amniotic fluid cells are cultured for fetal karyotype analysis. The karyotypes such as peripheral blood lymphocyte karyotypes are seen.
3. Fluorescence in situ hybridization hybridization with target cells using fluorescently labeled X-chromosome probe (DXZ1), the specific hybridization site is Xq13.2 region near the X chromosome centromere, and FISH can be seen in the cells of Turner syndrome patients. The hybridization signal disappears or weakens.
4. The blood gonadotropin FSH, LH increased significantly, E2 decreased, suggesting ovarian failure.
Abdominal pelvic B-ultrasound showed uterus, ovarian dysplasia, severe fibrous cord-like, echocardiographic examination of the presence of aortic valve dilobes, but no stenosis of the heart disease, imaging examination can be found in kidney deformity.
Diagnosis
Diagnosis and diagnosis of congenital ovarian hypoplasia in children
If the girl is found to have short stature, elbow valgus, neck sputum, no secondary sexual characteristics during puberty, and some congenital malformations, the disease should be suspected, and cytogenetic examination is required for diagnosis.
The following diseases should be considered in the differential diagnosis:
1. Pituitary dwarfism patients have no deformities, and their growth hormone secretion is insufficient. Some patients also have thyroid-stimulating hormone and adrenocortical hormone deficiency.
2. Delayed development of puberty Although puberty is delayed for several years compared with normal children, it can reach normal development level, and its endocrine function is normal, no blood TSH, LH is elevated.
3. Birth low birth weight infants are born in full term, but their body weight is significantly lower than normal children and their physical development is always lower than normal. Their growth hormone and bone age are close to normal, sometimes accompanied by some congenital malformations, which constitute various syndromes. However, there is no performance of Turner syndrome such as short neck, low hairline and elbow valgus.
4. The clinical manifestations of Noonan syndrome are similar to those of congenital ovarian hypoplasia. There are many patients with mental retardation. Some patients have cardiovascular malformation. Among them, pulmonary artery stenosis and atrial septal defect are the most common, and their karyotype is normal male or female.
