Prenatal diagnosis of chromosomal abnormalities. Markers of fetal chromosomal pathology in identifying Down syndrome

A chromosomal abnormality is any change in the number or structure of chromosomes. The most famous of them is trisomy on the 21st pair of chromosomes (Down syndrome or Mongolism). Besides this, there are many other anomalies. Some of them are incompatible with life and, as a rule, cause miscarriages, others lead to disturbances in psychomotor development of varying severity, and some changes do not have any adverse manifestations and do not affect a person’s life.

The only way to find out if your baby has such an anomaly is to perform a test such as amniocentesis or trophoblast biopsy, which will help determine the fetal karyotype. A karyotype is a child's genetic map. But such studies are carried out only in cases where the risk of a child having a chromosomal abnormality is significantly increased. Therefore, it is very important to accurately assess the likelihood of a chromosomal abnormality occurring.

There are many ways to calculate this risk. They are all well studied from a scientific point of view, but the best method is one that requires a minimum number of tests (and, therefore, allows you to reduce the frequency of unjustified miscarriages), and at the same time allows you to most accurately determine the risk of possible chromosomal abnormalities.

Taking these requirements into account, scientists recommend using a method for determining the degree of risk that takes into account the following three indicators:

Age-related risk expectant mother: It is known that the risk of developing a chromosomal abnormality increases with a woman’s age. For example, the probability of a chromosomal abnormality in a mother's fetus at age 20 is 1/1500, and by age 39 it increases to 1/128;

The degree of risk associated with the thickness of the nuchal fold of the fetus. This indicator is determined by a gynecologist during an ultrasound scan in the period from 11 to 13 weeks of amenorrhea;

The degree of risk is determined by the level of certain substances in the mother's blood in the first trimester of pregnancy (beta-hCG and PAPP-A protein).

This does not mean that your child has trisomy on the 21st pair of chromosomes, but starting from this (1/250) risk level, the gynecologist suggests amniocentesis.

It should be noted that amniocentesis is performed by only 5% of expectant mothers (of all age groups), and in 97% of cases in these 5% of women, the study does not reveal any abnormalities in the fetal karyotype. Which suggests that the risk of having a chromosomal abnormality is very small.

The final decision to perform amniocentesis or trophoblast biopsy is made only by the pregnant woman, who has every right to both agree to this study and refuse it. The doctor just helps the woman make this difficult decision.

To better understand the causes of chromosomal abnormalities that a specialist in the treatment of infertility may encounter in their practice, we will give a brief description of mitosis and meiosis. During mitosis, in somatic cells containing a diploid set of chromosomes (2n), DNA duplication occurs, which gives a tetraploid set (4n). After DNA replication, mitosis goes through the following stages: prophase, prometaphase, metaphase, anaphase and telophase. Each of the daughter cells is an exact copy of the parent.

Sex cells contain a haploid set of chromosomes (1n), which must be preserved until fertilization, in otherwise chromosomal abnormalities will occur.

It must be remembered that meiosis occurs differently in male and female germ cells. Oocytes of the first order in the fetus enter meiosis and stop in prophase I at the diplotene stage in the middle of the second trimester of pregnancy; meiosis resumes only in the dominant follicle immediately before ovulation. Under the influence of LH, the 1st division is completed, and the resulting second-order oocyte enters the 2nd division, which is completed after fertilization. In addition to the second-order oocyte, the first polar body is formed in the 1st division. In the 2nd division, an egg and a second polar body are formed from a second-order oocyte. In men, spermatozoa are formed only after the onset of puberty, and each first-order spermatocyte produces two second-order spermatocytes in the 1st division. In the 2nd division, each of them produces two spermatids, which later turn into mature sperm.

Disorders of mitosis and meiosis

Disturbances in meiosis lead to aneuploidy. In the case of nondisjunction of chromosomes, one of the daughter cells receives 22 chromosomes, which after fertilization produces an embryo with monosomy. The other daughter cell receives 24 chromosomes, resulting in trisomy after fertilization. If one of the chromosomes in anaphase does not separate from the spindle (chromosomal lag) and does not enter the daughter cell, fertilization of such a cell also leads to monosomy. The higher the age of the mother, the higher the probability of chromosome nondisjunction and, therefore, the occurrence of trisomy. Although it depends on the specific chromosome, in general, the majority of trisomies that doctors see are caused by disorders of the 1st meiotic division in women. If chromosome nondisjunction occurs in mitosis, two different cell clones may arise in the body (mosaicism). This can be observed with gonadal dysgenesis - non-disjunction of chromosomes in a zygote with karyotype 46,XY can give rise to cell clones with karyotypes 45,X and 47,XYY (all three cell clones may be present, depending on at what point the chromosome segregation is disrupted) . When chromosomes are delayed in the case of a 46,XY karyotype, mosaicism with a 45,X/46,XY karyotype is possible.

Indications for determining the karyotype

Mother's age

The frequency of chromosomal abnormalities associated with sex chromosomes - karyotypes 47,XXY and 47,XXX - is also increasing. In addition, it is extremely important to find out the presence of chromosomal abnormalities in close relatives - this may further increase the risk. If a given couple has already had trisomy during one of their previous pregnancies, the risk of its reoccurrence is about 1%. In addition, with the age of the mother, the risk of spontaneous abortion increases: in women under 30 years of age it is 10-15%, and by 40 years of age it gradually increases to 30-40%. This is largely due to the increasing frequency of chromosomal abnormalities in the fetus.

The age of the father, unlike the age of the mother, does not appear to influence the risk of trisomy. However, what older father, the higher the child's cumulative risk of autosomal dominant diseases such as Marfan syndrome, neurofibromatosis, achondroplasia and Apert syndrome. In addition, if such a couple has a daughter, then her sons will have an increased risk of X-linked recessive diseases (hemophilia A and B, Duchenne myopathy and others). However, the risk of any of these diseases in the absence of a family history is small, so regardless of the father's age, testing is not particularly worthwhile.

Spontaneous abortion, including habitual abortion

It is well known that during spontaneous abortion in the first trimester of pregnancy, approximately half of the embryos have chromosomal abnormalities. With spontaneous abortion at a later stage, the proportion of fetuses with chromosomal abnormalities is reduced: with an abortion at 12-15 weeks, they are detected in 40%, 16-19 weeks - in 20% of fetuses. In premature babies born at 20-23 weeks of gestation, the frequency of chromosomal abnormalities is 12%, at 24-28 weeks - 8%, at later stages - 5%, and in full-term babies - about 0.5%. It should be emphasized that these statistics do not apply to habitual spontaneous abortion (defined as two or more spontaneous abortions in a row). Unfortunately, it is possible that in these cases polyploidy, aneuploidy, or even a combination of one with the other may occur over and over again. Large studies involving large group There were no women with habitual spontaneous abortion. Boue et al. determined the karyotype of the fetus in 1500 spontaneous abortions and concluded that repeated cases of aneuploidy in habitual spontaneous abortion are unlikely to be widespread and are most likely due to coincidence. With a new conception in a couple who have had a spontaneous abortion with chromosomal abnormalities in the past, the risk of repeating such an abortion is not increased, which indicates the rarity of recurrent aneuploidy. Both studies suffer from sampling bias because the material was obtained from samples sent to a cytogenetics laboratory. A large prospective study is required to determine the karyotype of several fetuses from each participant suffering from recurrent spontaneous abortion.

In cases of habitual spontaneous abortion in both partners, two types of chromosomal translocations are detected more often than usual - Robertsonian and reciprocal; both of them can be compensated or de-compensated. With a compensated translocation, the phenotype is normal - there is no loss of chromosomal material or it is insignificant. Decompensated translocation often leads to unfavorable phenotypic manifestations, which often include mental retardation and various developmental defects.

Robertsonian translocations occur between acrocentric chromosomes (those with one arm much shorter than the other), namely 13, 14, 15, 21 and 22. In this case, the long arms of both chromosomes merge, and the genetic material from the short arms is presumably lost. In the case of compensated Robertsonian translocation, the karyotype contains 45 chromosomes. With decompensated translocation of chromosome 46, therefore, there is trisomy on one of the chromosomes involved in the translocation (on the long arm). In the case of such trisomy on chromosome 21, Down syndrome develops. Since decompensated translocation occurs in 3-4% of cases of Down syndrome, karyotyping of parents with Down syndrome in a child is necessary to assess the risk of re-birth of an affected child.

In a reciprocal translocation, two different chromosomes exchange genetic material. With a compensated translocation, there are 46 chromosomes in the karyotype, and with a decompensated translocation, there are deletions or duplications (partial monosomies and trisomies). Since translocations can result in the birth of both normal children and children with developmental defects, as well as spontaneous abortions, karyotyping is especially necessary in these cases.

The cause of habitual spontaneous abortion and spontaneous abortion in combination with severe fetal malformations may be the presence of a compensated translocation in any of the partners. In such cases, its frequency is approximately 4%, which is 10-30 times higher than normal. In the case of more frequent reciprocal translocation (about two thirds of cases in couples with recurrent abortion), this risk for most translocations is approximately the same, does not depend on which partner is a carrier, and is 5-20%. However, with the Robertsonian translocation, which affects chromosome 21, the risk is higher if the carrier of the translocation is a woman. If the mother has a Robertsonian translocation, the risk of having a child with Down syndrome is 10-15%, and if the father has it, it is 0-2%. For other Robertsonian translocations, the risk of chromosomal abnormalities in offspring is much lower.

Some researchers report that women with habitual spontaneous abortion often experience abnormal inactivation of the X chromosome. Normally, one of the X chromosomes is inactivated randomly, but marked deviations from this (for example, inactivation of the same X chromosome in more than 90% of cells) appear to be more common in women with recurrent abortion (about 15%). ) than in the control group (about 5%). It can be assumed that the X chromosome carrying the mutant allele is mainly inactivated (male embryos that inherited this X chromosome die). This hypothesis has not yet been proven, since not all researchers confirm the observations of an increased frequency of abnormal inactivation of the X chromosome in recurrent abortion.

Primary hypogonadism

Primary amenorrhea in combination with elevated levels of gonadotropic hormones in a woman of childbearing age should always serve as an indication for determining the karyotype. More than half of these women have chromosomal abnormalities, most often karyotype 46,XY (Swire syndrome) or 45,X (Turner syndrome). The presence of a Y chromosome is associated with a high risk of germ cell tumors: with Swire syndrome it reaches 20-25%, and with a karyotype of 45,X/46,XY - 15%. Women with a 45.X karyotype (including mosaicism) are most often of small stature (less than 160 cm in the presence of a Y chromosome and, as a rule, less than 150 cm in its absence), 90-95% of them do not have secondary sexual characteristics. In addition, in half of the cases of Turner syndrome, heart defects are detected (bicuspid aortic valve and aortic enlargement), and in 30% of cases, renal malformations are detected. Cases of aortic rupture have been described in women with Turner syndrome who became pregnant through IVF using donor eggs. Swire syndrome (gonadal dysgenesis with karyotype 46,XY) is characterized by normal growth, undeveloped mammary glands and cord-like gonads. Since the testicles do not function, anti-Mullerian hormone is not produced, and a full vagina and uterus develop.

With secondary amenorrhea, the likelihood of detecting a chromosomal abnormality is much lower, but in the presence of certain symptoms it increases. If the patient's height is less than 160 cm, a karyotype determination is indicated, since 5-10% of girls with Turner syndrome experience normal puberty and menarche. In addition, if a woman has a deletion on the X chromosome (usually the long arm), she can pass it on to her daughter, who will also have an increased risk of premature ovarian failure. Such women may exhibit a Turner syndrome phenotype, in particular, their height usually does not exceed 160 cm. In addition, in women with a karyotype of 46.XX, premature ovarian failure may indicate carriage of fragile X syndrome.

An increase in the level of gonadotropic hormones in men in approximately 10-15% of cases is associated with chromosomal abnormalities. Testosterone levels are usually low or close to the lower limit of normal, gonadotropin levels are elevated, and the testicles are small and firm. Klinefelter syndrome has an increased risk of diabetes, testicular tumors, and breast cancer, so men with this syndrome should be closely monitored. In men with a karyotype of 46.XX, primary hypogonadism is also observed; The reason for the appearance of the male phenotype is a translocation between the X and Y chromosomes in the 1st division of meiosis, as a result of which the sex determination gene (SRY) located on the short arm of the Y chromosome is transferred to the X chromosome. Since such men have a long arm of the Y chromosome, on which spermatogenesis genes are presumably located, they have azoospermia.

In case of secondary hypogonadism in both men and women, it usually makes sense to determine the karyotype only in case of multiple malformations or if Prader-Willi syndrome is suspected.

Severe oligozoospermia or azoospermia

In case of severe oligozoospermia or azoospermia, the karyotype is also determined: occasionally, chromosomal abnormalities, most often translocations, are detected. They are rarely the cause of oligozoospermia or azoospermia, but if conception is achieved, with chromosomal abnormalities there is a risk of spontaneous abortion and, more importantly, the birth of a child with developmental defects. Rarely with severe oligozoospermia in men with normally developed secondary sexual characteristics and normal levels gonadotropic hormones show a karyotype of 47,XXY.

Multiple malformations

With multiple malformations and mental retardation, chromosomal abnormalities are often detected, therefore, in such cases, determination of the karyotype is indicated. In addition to trisomies, partial deletions can be found in autosomes (including in the long arm of the 18th and 13th chromosomes).

• The essence of diseases
• Causes
• Signs
• Diagnostic methods
• Decoding and calculating risks
• Forecasts
• Diseases

During pregnancy, various tests and studies can diagnose chromosomal pathologies of the fetus, which are essentially hereditary diseases. They are caused by changes in the structure or number of chromosomes, which explains their name.

The main cause of occurrence is mutations in the germ cells of the mother or father. Of these, only 3-5% are inherited. Due to such deviations, about 50% of abortions and 7% of stillbirths occur. Since these are serious gene defects, parents should be more attentive to all tests prescribed throughout pregnancy, especially if they are at risk.

The essence of diseases

If parents (both) have hereditary diseases in their family, they first need to know what it is - chromosomal pathologies of the fetus, which can be detected in their child while he is still in the womb. Awareness will allow you to avoid unwanted conception, and if this has already happened, eliminate the most severe consequences, ranging from intrauterine death the baby and ending with external mutations and deformities after his birth.

In a normal, healthy person, chromosomes are arranged in 23 pairs, and each is responsible for a specific gene. The total is 46. If their number or structure is different, they speak of chromosomal pathologies, of which there are many varieties in genetics. And each of them entails dangerous consequences for the life and health of the baby. The main causes of this type of anomaly are unknown, but there are certain risk groups.

With the world on a thread. One of the rarest chromosomal pathologies is called cry-the-cat syndrome. The reason is a mutation on chromosome 5. The disease manifests itself in the form of mental retardation and the characteristic crying of a child, which is very reminiscent of a cat's cry.

Causes

In order to prevent or promptly recognize chromosomal pathologies of the fetus during pregnancy, doctors must interview future parents about hereditary diseases and the living conditions of their family. According to recent studies, gene mutations depend on this.

There is a certain risk group, which includes:

• the age of the parents (both) is over 35 years;
• the presence of CA (chromosomal abnormalities) in blood relatives;
• harmful working conditions;
• long-term residence in an environmentally unfavorable area.

In all these cases, there is a fairly high risk of chromosomal pathology of the fetus, especially in the presence of hereditary diseases at the gene level. If these data are identified in a timely manner, doctors are unlikely to advise the couple to give birth at all. If conception has already occurred, the degree of damage to the child, his chances of survival and a further full life will be determined.

Mechanism of occurrence. Chromosomal pathologies develop in the fetus when a zygote is formed and the fusion of sperm and egg occurs. This process cannot be controlled because it has not yet been studied enough.

Signs

Since the process of occurrence and development of this type of abnormality has not been sufficiently studied, markers of chromosomal pathology of the fetus are considered conditional. These include:

• threat of miscarriage, nagging pain in the lower abdomen early stages pregnancy;
• low levels of PAPP-A (plasma protein A) and AFP (protein produced by the embryo's body), elevated hCG(chorionic gonadotropin - placental hormone): to obtain such data, blood is taken from a vein to determine the chromosomal pathology of the fetus at 12 weeks (+/- 1-2 weeks);
• length of nasal bones;
• enlarged neck fold;
• fetal inactivity;
• enlarged renal pelvis;
• slow growth of tubular bones;
• early aging or hypoplasia of the placenta;
• fetal hypoxia;
• poor results of Doppler (ultrasound method for identifying circulatory pathologies) and CTG (cardiotocography);
• oligohydramnios and polyhydramnios;
• hyperechoic intestine;
• small size of the maxillary bone;
• enlarged bladder;
• cysts in the brain;
• swelling in the back and neck;
• hydronephrosis;
• facial deformities;
• umbilical cord cysts.

The ambiguity of these signs is that each of them separately, like the entire complex listed above, can be the norm, determined by the individual characteristics of the mother or child. The most accurate and reliable data is usually provided by a blood test for chromosomal pathologies, ultrasound and invasive techniques.

Through the pages of history. Examining chromosomes modern people, scientists have found that they all received their DNA from one woman who lived somewhere in Africa 200,000 years ago.

Diagnostic methods

The most informative method for diagnosing chromosomal pathologies of the fetus is the first screening (it is also called a double test). Done at 12 weeks of pregnancy. It includes:

• Ultrasound (the markers indicated above are identified);
• blood test (taken from a vein on an empty stomach) showing the level of AFP, hCG, APP-A.

It should be understood that this analysis for chromosomal pathologies of the fetus cannot provide an accurate, 100% confirmation or refutation of the presence of anomalies. The doctor’s task at this stage is to calculate the risks, which depend on the research results, age and medical history of the young mother. The second screening (triple test) is even less informative. The most accurate diagnosis is invasive methods:

• chorionic villus biopsy;
• umbilical cord blood collection;
• amniotic fluid analysis.

The purpose of all these studies is to determine the karyotype (the set of characteristics of a set of chromosomes) and, in connection with this, chromosomal pathology. In this case, the accuracy of diagnosis is up to 98%, while the risk of miscarriage is no more than 2%. How is the data obtained during these diagnostic techniques deciphered?

Ultrasound and risks to the fetus. Contrary to the widespread myth about the dangers of ultrasound for the fetus, modern equipment makes it possible to reduce negative impact Ultrasound waves on the baby to zero. So don't be afraid of this diagnosis.

Decoding and calculating risks

After the first double screening is done, ultrasound markers of fetal chromosomal pathology that were identified during the study are analyzed. Based on them, it calculates the risk of developing genetic abnormalities. The very first sign is an abnormal size of the collar space in an unborn child.

Ultrasonic markers

Absolutely all ultrasound markers of chromosomal pathology of the fetus in the 1st trimester are taken into account in order to make the necessary calculations of possible risks. After that clinical picture supplemented by a blood test.

Blood markers

All other indicators are considered deviations from the norm.

In the second trimester, inhibin A, unconjugated estriol and placental lactogen are also assessed. All interpretation of the research results is carried out by a special computer program. Parents can see the following values ​​as a result:

• 1 in 100 means that the risk of genetic defects in the baby is very high;
• 1 in 1000 is the threshold risk of chromosomal pathology of the fetus, which is considered normal, but a slightly underestimated value may mean the presence of some anomalies;
• 1 in 100,000 is a low risk of chromosomal pathology of the fetus, so there is no need to worry about the baby’s health from a genetic point of view.

After doctors calculate the risk of chromosomal pathology in the fetus, either additional tests are prescribed (if the obtained value is lower than 1 in 400), or the woman calmly nurses the pregnancy to a successful outcome.

This is interesting! The male Y chromosome is the smallest of all. But it is precisely this that is passed on from father to son, preserving the continuity of generations.

Forecasts

Parents whose child was diagnosed with chromosomal abnormalities in utero should understand and accept as a given that they cannot be treated. All that medicine can offer them in this case is an artificial termination of pregnancy. Before making such a responsible decision, you need to consult your doctors on the following issues:

• What exactly pathology was diagnosed?
• What consequences will it have for the life and health of the child?
• Is there a high risk of miscarriage and stillbirth?
• How old do children with this diagnosis live?
• Are you ready to become parents of a disabled child?

In order to make the right decision about whether to keep a sick baby or not, you need to objectively evaluate all the possible consequences and results of chromosomal pathology of the fetus together with a doctor. They largely depend on what kind of genetic abnormality doctors suspect. After all, there are quite a lot of them.

Interesting fact. Patients with Down syndrome are commonly called sunny people. They are rarely aggressive, most often very friendly, sociable, smiling and even talented in some ways.

Diseases

The consequences of chromosomal pathologies detected in the fetus can be very different: from external deformities to damage to the central nervous system. They largely depend on what kind of anomaly has occurred with the chromosomes: their number has changed or mutations have affected their structure. Among the most common diseases are the following.

Chromosome number disorder

• Down syndrome is a pathology of the 21st pair of chromosomes, in which there are three chromosomes instead of two; accordingly, such people have 47 of them instead of the normal 46; typical signs: dementia, delayed physical development, flat face, short limbs, open mouth, squint, bulging eyes;
• Patau syndrome - disturbances in the 13th chromosome, a very severe pathology, as a result of which numerous developmental defects are diagnosed in newborns, including idiocy, polyfingeredness, deafness, mutations of the genital organs; such children rarely live to be one year old;
• Edwards syndrome - problems with the 18th chromosome, often associated with the mother's advanced age; babies are born with a small lower jaw and mouth, narrow and short eye slits, and deformed ears; 60% of sick babies die before 3 months, and 10% survive up to a year; the main causes of death are respiratory arrest and heart defects.

Violation of the number of sex chromosomes

• Shereshevsky-Turner syndrome - abnormal formation of the gonads (most often in girls), caused by the absence or defects of the sex X chromosome; symptoms include sexual infantilism, folds of skin on the neck, deformation of the elbow joints; children with such a chromosomal pathology survive, although childbirth is very difficult, and in the future, with proper supportive treatment, women are even able to carry their own baby (through IVF);
• polysomy on the X- or Y-chromosome - a variety of chromosome disorders, characterized by a decrease in intelligence, an increased likelihood of developing schizophrenia and psychosis;
• Klinefelter syndrome is a disorder of the X chromosome in boys, who in most cases survive after childbirth, but have a specific appearance: lack of body hair, infertility, sexual infantilism, mental retardation (not always).

Polyploidy

• Such chromosomal pathology in the fetus always ends in death even before birth.

Scientists are still trying to figure out why gene mutations occur at the chromosome level. However, this is still only a matter of the future, and at this point in time, chromosomal pathologies detected in utero in the fetus account for up to 5% of all cases.

What should parents do when they hear such a diagnosis? Do not panic, reconcile yourself, listen to the doctors and, together with them, make the right decision - leave the sick baby or agree to an artificial termination of pregnancy.

Under congenital anomalies refers to the pathology of embryo development from the moment of fertilization to the onset of labor, and, depending on the timing of its occurrence, the following forms are distinguished: gametopathies ( pathological changes in germ cells that occurred before fertilization, and which can lead to unexpected abortion, congenital malformations, hereditary diseases), blastopathy (damage to the zygote in the first two weeks after fertilization, leading to the death of the embryo, ectopic pregnancy, to congenital malformations), embryopathy (damage to the embryo from the 15th day after fertilization until the formation of the placenta - 75 days, congenital malformations of individual organs and systems may occur, termination of pregnancy), fetopathy (pathology that occurs from the 76th day until birth, manifests itself intrauterine growth retardation, congenital malformations, preservation of the original location of organs, underdevelopment of organs, congenital diseases, as well as premature birth, asphyxia at birth).

Causes of developmental defects.

These reasons are very varied. But most often these are diseases of the mother of various organs and systems, endocrine pathologies, infectious diseases, both chronic and existing before pregnancy, and those that developed during pregnancy; obstetric and gynecological pathology of the mother (abortions that occurred before pregnancy, long-term threats of termination of pregnancy, especially in the early stages, prolonged or severe toxicosis, and others). Environmental factors and other harmful effects on the pregnant woman’s body and fetus also play a huge role: physical (various radiation, temperature), chemical (industrial and household chemicals, medications - more about them below, alcohol, nicotine and other drugs), biological factors(infections and their toxins). The role of hereditary factors (various chromosomal aberrations and gene mutations) is also great. It should also be noted the particularly important role of a balanced diet without a deficiency of not only the main food ingredients (proteins, fats, carbohydrates, minerals, vitamins), but also micronutrients (microelements, polyunsaturated omega fatty acids and others) both during pregnancy and during pregnancy planning. For example, iodine deficiency in a woman before conception and in early pregnancy can lead to fetal hypothyroidism and disorders of brain development. Risk factors and possible pathology of newborns, on the maternal side:

• age over 35 years – chromosomal abnormalities, intrauterine growth retardation;
• age under 16 years – prematurity;
• low socioeconomic status – prematurity, intrauterine growth retardation, infections;
• folic acid deficiency – congenital malformations;
• smoking – intrauterine growth retardation, increased prenatal mortality;
• alcohol or drug use - intrauterine growth retardation, fetal alcohol syndrome, withdrawal syndrome, syndrome sudden death;
• diabetes mellitus – stillbirth, high body weight, congenital malformations;
• diseases of the thyroid gland - goiter, hypothyroidism, thyrotoxicosis;
• kidney diseases - intrauterine growth retardation, stillbirth, nephropathy;
• diseases of the lungs and heart - intrauterine growth retardation, prematurity, congenital heart defects;
• arterial hypertension - intrauterine growth retardation, asphyxia;
• anemia - intrauterine growth retardation, stillbirth;
• polyhydramnios – congenital malformations of the kidneys, central nervous system, gastrointestinal tract;
• low level of estriol in urine – intrauterine growth retardation;
• bleeding – prematurity, stillbirth, anemia;
• infections, especially toxoplasmosis, rubella, herpes - intrauterine growth retardation, congenital malformations, encephalopathy, pneumonia.

From the fetus:

• multiple pregnancy – prematurity, fetofetal transfusion, asphyxia;
• intrauterine growth retardation - asphyxia, stillbirth, congenital malformations;
• anomalies of fetal presentation - trauma, hemorrhage, congenital malformations.

• premature birth - asphyxia;
• delayed birth (2 or more weeks) – stillbirth, asphyxia;
• prolonged labor – stillbirth, asphyxia;
• prolapse of the umbilical cord - asphyxia.

Abnormalities of the placenta:

• small placenta – intrauterine growth retardation;
• large placenta – fetal hydrops, heart failure;
• premature placental abruption – blood loss, anemia;
• placenta previa – blood loss, anemia.

The effect on the fetus and newborn of medications used by a woman during pregnancy:

aloe enhances intestinal motility, aminoglycosides (streptomycin, gentamicin, kanamycin and others) have a toxic effect on the ear and kidneys, androgens cause various malformations, antihistamines lower blood pressure, cause tremor, indirect anticoagulants cause nasal hypoplasia, disrupt fetal bone formation, and can cause encephalopathy , atropine depresses breathing, barbiturates can cause minor cerebral dysfunction, belladonna drugs - tachycardia, blood pressure lowering drugs - worsen blood flow between the child and the placenta, diazepam - muscle hypotension, hypothermia, apnea, cleft lip and nose, isoniazid - convulsions, indomethacin - pulmonary hypertension, premature closure of the ductus arteriosus, corticosteroids - encephalopathy, inhibition of fetal adrenal function, caffeine - liver damage, xanthines - tachycardia, lithium - lethargy, congenital heart defects, burnt magnesia - kidney damage, nitrofurans - hemolysis of red blood cells, obzidan - prolongation of labor, opiates – depress breathing, minor cerebral dysfunction, anticonvulsants – intrauterine growth retardation, malformations, reserpine disrupts nasal breathing, salicylates – bleeding, seduxen causes respiratory depression, lowers blood pressure, theophylline – disrupts blood clotting, phenothiazines – muscle hypotonia, tetracyclines – multiple bone abnormalities and skeleton. Possible developmental defects, depending on the time of exposure to the factors listed above:

• in the third week of pregnancy, the fetus may develop ectopia of the heart, hernia of the umbilical cord, congenital absence of limbs, fusion of the feet;
• in the fourth week from the moment of fertilization, a hernia of the umbilical cord, congenital absence of feet, tracheoesophageal fistula, hemivertebra may appear;
• in the fifth week of development - tracheoesophageal fistula, hemivertebra, central cataract, microphthalmia, splitting of the facial bones, absence of the hand and foot;
• in the sixth week - absence of the hand and foot, microphthalmia, congenital absence of the lower jaw, lenticular cataract, congenital heart defects (septum and aorta);
• seventh week – congenital heart defects (interventricular septum, pulmonary artery), absence of fingers, cleft palate, micrognathia, epicanthus, round head;
• in the eighth week - congenital heart defects (atrial septal defect), epicanthus, round head, absence of nasal bone, shortening of fingers.

As you can see, the causes and anomalies themselves can be very diverse.

Diagnosis of congenital anomalies.

The main task of diagnosis during pregnancy is to identify chromosomal pathologies or fetal malformations. There are many diagnostic medical and genetic methods for recognizing certain developmental defects, these are non-invasive diagnostic methods:

• ultrasound examination method (which is carried out for all pregnant women no earlier than 3 times during pregnancy: at 10-12 weeks, 20-22 weeks, 30-32 weeks, in this case ancephaly, undivided fetuses, amelia and many others can be diagnosed),
• determination of various biochemical markers in the mother's blood serum: plasma protein A, human chorionic gonadotropin (with an ectopic pregnancy, the rate of increase in this marker will not correspond to the norm, and changes in this hormone may indicate chromosomal disorders), alpha-fetoprotein (increasing its level increases the risk of developing open defects of the central nervous system; if its level decreases, there may be a risk of developing Down syndrome), estriol (it should increase as pregnancy progresses).

The following are considered invasive:

• Chorionic villus biopsy (removal of some cells ovum for research, carried out at 11–12 weeks, genetic pathology is detected),
• amniocentesis (sampling of amniotic fluid, in the first trimester of pregnancy adrenal hyperplasia is detected, in the second trimester - chromosomal pathology, diseases of the nervous system),
• placentocentesis (examination of placental particles, from 12 to 22 weeks, genetic pathology),
• cordocentesis (blood sampling from the fetal umbilical cord for research, blood diseases and fetal infection are detected),
• fetal skin biopsy (for diagnosis possible diseases skin).

To diagnose anomalies after birth, all known research methods can be used: radiation (radiography, computed tomography, magnetic resonance imaging, radioisotope, ultrasound, angiography and others), endoscopic (bronchoscopy, gastroscopy), various studies of blood, urine and other biological fluids , multiple functional assays and tests, genetic, molecular, immune methods and much, much more. Since for anomalies of various systems and organs it will be necessary different methods research.

Indications for termination of pregnancy.

Various dysfunctions of the mother’s organs and systems can cause termination of pregnancy, and this is associated not only with a risk to the health and life of the mother, but also for the unborn child, since these diseases and their treatment can negatively affect him. But the final decision is always made individually. Here are some diseases that can cause termination of pregnancy: infectious (active form of tuberculosis, severe forms of viral hepatitis, syphilis, rubella), malignant neoplasms (almost all, they are not only an indication for termination, but a contraindication for pregnancy in general), diseases endocrine system(severe form of thyrotoxicosis, uncompensated hypothyroidism, severe form of diabetes mellitus), diseases of the blood and hematopoietic organs (aplastic anemia, hemoglobinopathies, leukemia), neurological diseases (multiple sclerosis, myasthenia gravis), eye diseases (diseases of the optic nerve and retina), cardiovascular diseases vascular system (deep vein thrombosis, thromboembolism, heart defects), kidney diseases (acute glomerulonephritis, urolithiasis), diffuse connective tissue diseases, gynecological diseases, obstetric indications (gestational trophoblastic disease, excessive vomiting of pregnant women, untreatable gestosis, congenital defects and hereditary diseases that were diagnosed during pregnancy, a high risk of having a child with a congenital, hereditary pathology). But it should be noted that abortion medical indications requires mandatory consent from the patient. If any malformations of the fetus are detected, the pregnant woman herself decides whether to continue the pregnancy or have an abortion.

Prevention of congenital anomalies.

Here the main activity should be family planning and pregnancy. Not only the success of conception itself, but the development of pregnancy itself, childbirth and the health of the child throughout his future life depends on the quality of this event. It is necessary to be tested for the presence of sexually transmitted diseases, for the presence of hidden infections, to identify all possible chronic diseases, not only in the expectant mother, but also in the father, to undergo genetic testing (to find out what diseases the child may develop, to identify various genetic diseases in previous generations ). Naturally, the main factor in the development of a healthy, full-fledged fetus is a healthy lifestyle, not only during pregnancy, but also before its onset. Giving up bad habits, eating well, eliminating all harmful factors physical, chemical, biological nature. Timely treatment of existing diseases to avoid complications during pregnancy. During pregnancy itself, undergo the necessary examinations in order to timely identify any abnormalities in normal development fetus

Pregnancy is a long-awaited state for a woman. However, this is also a period of worry. After all, the normal course of pregnancy is far from a guarantee that the baby will be born without pathologies. At an early stage, diagnostic measures are required to help exclude chromosomal pathologies. Fetal chromosomal abnormalities are the appearance of an additional (extra) chromosome or a disturbance in the structure of one of the chromosomes. This happens even during intrauterine development. So, everyone knows about Down syndrome. This is a disease that develops in utero. It is associated with the appearance extra chromosome directly in 21 pairs. Thanks to diagnostics, as well as external manifestations of the course of pregnancy, it is possible to identify such a pathology in the early stages of fetal development.

Causes of chromosomal abnormalities

Chromosomal defects can develop for various reasons. Often these are health problems in the mother:

• infections;
• problems with the endocrine system;
• diseases of any internal organs;
• toxicosis during pregnancy;
• previous abortions;
• risk of miscarriage.

An important role is played by ecology, which constantly affects the woman’s body, as well as environmental features:

• chemical factors (food, medicine, nicotine, drugs, and alcohol);
• physical factors (temperature, radiation);
• biological factors in the form of infections and toxins.

The hereditary factor is also important. Gene mutations, chromosome aberrations – common reasons development of anomalies. Already when planning a pregnancy, you need to think about a balanced diet:

1. All main ingredients must be present in the menu in sufficient quantities (vitamins, fats, minerals, carbohydrates and proteins).
2. You need to make sure that the menu contains products with micronutrients (polyunsaturated fatty acids, microelements important for the body). Thus, a deficiency of an element such as iodine in the body can lead to impaired brain development of the unborn child.

Risk factors

There are many risk factors for developing chromosomal abnormalities. On the mother's side these are problems such as:

• Smoking. Leads to delayed fetal development.
• Age less than 16 years. May lead to prematurity.
• Age over 35 years. Often leads to developmental delay and chromosomal abnormalities.
• Use of drugs or alcoholic beverages. It is the cause of sudden death syndrome, fetal alcohol syndrome and withdrawal syndrome.
• Thyroid diseases.
• Diabetes mellitus often leads to congenital malformations.
• Kidney problems.
• Diseases of the heart and lungs lead to congenital heart defects.
• Anemia.
• Hypertension.
• Polyhydramnios is the cause of defects of some internal organs.
• Bleeding.
• Infectious diseases.

There are also risks from the fetus:

• Developmental delay.
• Multiple pregnancy.
• Abnormalities in presentation.

Medicines, pregnancy and chromosomal pathologies

Many medications that a woman takes during pregnancy affect the fetus:

• aminoglycosides have a toxic effect on ear and kidney development;
• aloe promotes increased intestinal motility;
• antihistamines can cause tremors and significantly reduce blood pressure;
• androgens are the cause of the development of fetal defects;
• anticoagulants can cause problems with bone formation, as well as encephalopathy;
• atropine is a cause of brain dysfunction;
• belladonna causes tachycardia in the fetus;
• blood pressure lowering agents significantly reduce blood flow to the placenta;
• diazepam can harm the appearance of the unborn child;
• corticosteroids inhibit the functional purpose of the adrenal glands, leading to encephalopathy;
• caffeine damages the fetal liver;
• lithium develops heart defects;
• Opiates affect brain activity;
• anticonvulsants significantly delay intrauterine development baby;
• tetracyclines lead to skeletal abnormalities.

Signs

The process of development of anomalies in intrauterine state Today it has not been studied enough. That is why signs of anomalies are considered conditional. Among them:

• in early pregnancy, nagging pain in the lower abdomen;
• risk of miscarriage;
• non-standard length of nasal bones;
• low levels of AFP and PAPP-A, as well as increased level HCG. To see these indicators, at 12 weeks a pregnant woman is prescribed a test - blood from a vein;
• fetal inactivity;
• slow development of tubular bones;
• the neck fold is larger than normal;
• the renal pelvis is enlarged;
• hypoxia;
• polyhydramnios;
• oligohydramnios;
• Doppler and CTG with poor performance;
• large bladder;
• hydronephrosis;
• the presence of cysts in the brain;
• hyperechoic intestine;
• facial deformities;
• cysts in the umbilical cord area;
• swelling of the neck and back.

All these signs can be the norm for the development of the fetus, provided that the body of the child or mother has a similar characteristic. Blood tests, invasive techniques and ultrasound will help make sure that chromosomal abnormalities are present as accurately as possible.

Diagnostics

The main task of diagnostic measures that are prescribed during pregnancy is to identify fetal malformations. Today there are a huge number of methods that allow you to accurately diagnose or exclude the presence of anomalies. Non-invasive methods:

• Ultrasound is prescribed 3 times throughout the pregnancy (up to 12 weeks, at 20-22 weeks and 30-32 weeks).
• Determination of biochemical markers in blood serum. HCG, protein A - deviations from the norm may indicate an ectopic pregnancy or the development of chromosomal disorders. Alpha-fetoprotein - a reduced level indicates a risk of developing Down syndrome, and an increased level indicates a possible defect of the central nervous system. Estriol - normally should gradually increase with increasing pregnancy.

Invasive techniques:

• Chorionic villus sampling to identify a genetic abnormality. In this case, a small part of the cells of the fetal egg is taken for analysis.
• Placentocentesis is the examination of the placenta. It is performed at 12-22 weeks of pregnancy if genetic pathologies are suspected.
• Amniocentesis - analysis of amniotic fluid is performed in the first trimester of pregnancy. Identifies chromosomal pathologies and nervous system problems.
• Cordocentesis is a test of blood from the umbilical cord to determine blood diseases and the presence of infections in the fetus.
• Skin biopsy to diagnose skin problems.

After the birth of a child, any methods from the arsenal of modern medicine can be used to determine anomalies:

• radiation methods (CT, CTG, X-ray, ultrasound);
• endoscopic;
• research of biological materials;
• functional tests.

Possible pathologies

The development of many anomalies is observed during specific periods of pregnancy:

• 3 weeks – ectopia of the heart, absence of limbs, and fusion of the feet;
• 4 weeks – absence of feet, hemivertebra;
• 5 weeks – splitting of the facial bones, as well as such terrible problems as the absence of hands and feet;
• 6 weeks – complete absence of the lower jaw, as well as heart disease, lenticular cataract;
• 7 weeks – absolute absence of fingers, development of a round head, incorrigible cleft palate above, as well as epicanthus;
• 8 weeks – absence of the nasal bone, shortening of the fingers.

The consequences of the development of chromosomal problems are very diverse. These can be not only external deformities, but also lesions and disturbances in the functioning of the central nervous system. The pathologies that arise depend on what kind of chromosome abnormality occurred:

1. If the quantitative characteristics of chromosomes are disturbed, Down syndrome may occur (in 21 pairs there is one extra chromosome), Patau syndrome (a severe pathology with numerous defects), Edwards syndrome (often appears in children of elderly mothers).
2. Violation of the number of sex chromosomes. Then the development of Shereshevsky-Turner syndrome (development of the gonads according to the wrong type) is likely; polysomies are characterized different problems, Klinefelter syndrome (disorders specifically in boys on the X chromosome).
3. Polyploidy usually ends in death in the womb.

Gene mutations have not yet been fully studied by scientists. The reasons for their development are still being investigated by specialists. But already 5% of all pregnant women in the world have genetic abnormalities of the fetus.

Approximately 1 in 150 children are born with chromosomal abnormality. These disorders are caused by errors in the number or structure of chromosomes. Many children with chromosomal problems have mental and/or physical birth defects. Some chromosomal problems ultimately lead to miscarriage or stillbirth.

Chromosomes are thread-like structures found in the cells of our body and containing a set of genes. Humans have about 20–25 thousand genes that determine characteristics such as eye and hair color, and are also responsible for the growth and development of every part of the body. Each person normally has 46 chromosomes, assembled into 23 chromosome pairs, in which one chromosome is inherited from the mother, and the second is inherited from the father.

Causes of chromosomal abnormalities

Chromosomal abnormalities are usually the result of an error that occurs during the maturation of a sperm or egg. Why these errors occur is not yet known.

Eggs and sperm normally contain 23 chromosomes. When they come together, they form a fertilized egg with 46 chromosomes. But sometimes something goes wrong during (or before) fertilization. For example, an egg or sperm may develop incorrectly, as a result of which they may have extra chromosomes, or, conversely, they may lack chromosomes.

In this case, cells with the wrong number of chromosomes are attached to a normal egg or sperm, as a result of which the resulting embryo has chromosomal abnormalities.

Most common type chromosomal abnormality called trisomy. This means that instead of having two copies of a particular chromosome, a person has three copies. For example, people with Down syndrome have three copies of chromosome 21.

In most cases, an embryo with the wrong number of chromosomes does not survive. In such cases, the woman has a miscarriage, usually in the early stages. This often occurs very early in pregnancy, before the woman may even realize she is pregnant. More than 50% of miscarriages in the first trimester are caused by chromosomal pathologies in the embryo.

Other errors may occur before fertilization. They can lead to changes in the structure of one or more chromosomes. People with structural chromosomal abnormalities usually have a normal number of chromosomes. However, small pieces of a chromosome (or an entire chromosome) may be deleted, copied, reversed, misplaced, or exchanged with part of another chromosome. These structural rearrangements may not have any effect on a person if he has all the chromosomes, but they are simply rearranged. In other cases, such rearrangements can lead to pregnancy loss or birth defects.

Errors in cell division can occur soon after fertilization. This can lead to mosaicism, a condition in which a person has cells with different genetic makeups. For example, people with one form of mosaicism, Turner syndrome, lack an X chromosome in some, but not all, cells.

Diagnosis of chromosomal abnormalities

Chromosomal abnormalities can be diagnosed before the baby is born through prenatal testing, such as amniocentesis or chorionic villus sampling, or after birth using a blood test.

The cells obtained from these tests are grown in the laboratory and then their chromosomes are examined under a microscope. The laboratory makes an image (karyotype) of all of a person's chromosomes, arranged in order from largest to smallest. A karyotype shows the number, size and shape of chromosomes and helps doctors identify any abnormalities.

The first prenatal screening consists of taking a maternal blood test in the first trimester of pregnancy (between 10 and 13 weeks of pregnancy), as well as a special ultrasound examination of the back of the baby's neck (the so-called nuchal translucency).

The second prenatal screening is carried out in the second trimester of pregnancy and consists of a maternal blood test between 16 and 18 weeks. This screening identifies pregnancies that are at higher risk for having genetic disorders.

However, screening tests cannot accurately diagnose Down syndrome or other chromosomal abnormalities. Doctors suggest that women who have abnormal screening test results undergo additional tests - chorionic villus sampling and amniocentesis - to definitively diagnose or rule out these disorders.

The most common chromosomal abnormalities

The first 22 pairs of chromosomes are called autosomes or somatic (non-sex) chromosomes. The most common abnormalities of these chromosomes include:

1. Down syndrome (trisomy 21) is one of the most common chromosomal abnormalities, diagnosed in approximately 1 in 800 babies. People with Down syndrome have varying degrees of mental development, characteristic facial features and, often, congenital abnormalities in the development of the heart and other problems.

Modern prospects for the development of children with Down syndrome are much brighter than they were before. Most of them have mild to moderate intellectual disabilities. Given that early intervention and special education, many of these children learn to read and write and participate in various activities from childhood.

The risk of Down syndrome and other trisomies increases with maternal age. The risk of having a child with Down syndrome is approximately:

• 1 in 1300 – if the mother is 25 years old;
• 1 in 1000 – if the mother is 30 years old;
• 1 in 400 – if the mother is 35 years old;
• 1 in 100 – if the mother is 40 years old;
• 1 in 35 – if the mother is 45 years old.

2. Trisomy 13 and 18 chromosomes– these trisomies are usually more serious than Down syndrome, but fortunately are quite rare. About 1 in 16,000 babies are born with trisomy 13 (Patau syndrome), and 1 in 5,000 babies are born with trisomy 18 (Edwards syndrome). Children with trisomy 13 and 18 typically suffer from severe mental retardation and many birth defects. Most of these children die before the age of one year.

The last, 23rd pair of chromosomes are the sex chromosomes, called the X chromosomes and the Y chromosomes. Typically, women have two X chromosomes, while men have one X chromosome and one Y chromosome. Sex chromosome abnormalities can cause infertility, growth problems, and learning and behavior problems.

The most common sex chromosome abnormalities include:

1. Turner syndrome– This disorder affects approximately 1 in 2,500 female fetuses. A girl with Turner syndrome has one normal X chromosome and is completely or partially missing a second X chromosome. Typically, these girls are infertile and will not undergo the changes of normal puberty unless they take synthetic sex hormones.

Girls affected by Turner syndrome are very short, although treatment with growth hormone may help increase height. In addition, they have a whole range of health problems, especially with the heart and kidneys. Most girls with Turner syndrome have normal intelligence, although they experience some learning difficulties, especially in mathematics and spatial reasoning.

2. Trisomy X chromosome– About 1 in 1000 women have an extra X chromosome. Such women are very tall. They typically have no physical birth defects, experience normal puberty, and are fertile. Such women have normal intelligence, but may also have serious problems with learning.

Since such girls are healthy and have a normal appearance, their parents often do not know that their daughter has chromosomal abnormalities. Some parents find out that their child has a similar disorder if the mother underwent one of the invasive prenatal diagnostic methods (amniocentesis or choriocentesis) during pregnancy.

3. Klinefelter syndrome– This disorder affects approximately 1 in 500 to 1000 boys. Boys with Klinefelter syndrome have two (and sometimes more) X chromosomes along with one normal Y chromosome. Such boys usually have normal intelligence, although many have problems with learning. When such boys grow up, they have decreased testosterone secretion and are infertile.

4. Disomy on the Y chromosome (XYY)– About 1 in 1,000 men are born with one or more extra Y chromosomes. These men experience normal puberty and are not infertile. Most have normal intelligence, although there may be some learning difficulties, behavioral difficulties and problems with speech and language acquisition. As with trisomy X in women, many men and their parents do not know they have the disorder until prenatal diagnosis.

Less common chromosomal abnormalities

New methods of chromosome analysis can detect tiny chromosomal abnormalities that cannot be seen even under a powerful microscope. As a result, more and more parents are learning that their child has a genetic abnormality.

Some of these unusual and rare anomalies include:

• Deletion – absence of a small section of a chromosome;
• Microdeletion - the absence of a very small number of chromosomes, perhaps only one gene is missing;
• Translocation - part of one chromosome joins another chromosome;
• Inversion - part of the chromosome is skipped, and the order of the genes is reversed;
• Duplication (duplication) - part of the chromosome is duplicated, which leads to the formation of additional genetic material;
• Ring Chromosome – When genetic material is removed from both ends of the chromosome and the new ends join together to form a ring.

Some chromosomal pathologies are so rare that only one or a few cases are known to science. Some abnormalities (for example, some translocations and inversions) may have no effect on a person's health if non-genetic material is missing.

Some unusual disorders may be caused by small chromosomal deletions. Examples are:

• Cry Cat Syndrome(deletion on chromosome 5) - sick children in infancy are distinguished by a high-pitched cry, as if a cat is screaming. They have significant problems in physical and intellectual development. Approximately 1 in 20–50 thousand babies are born with this disease;
• Prader-Will syndromeAnd(deletion on chromosome 15) – sick children have deviations in mental development and learning, short stature and behavior problems. Most of these children develop extreme obesity. Approximately 1 in 10–25 thousand babies are born with this disease;
• DiGeorge syndrome(chromosome 22 deletion or 22q11 deletion) – About 1 in 4,000 babies are born with a deletion in a specific part of chromosome 22. This deletion causes various problems which may include heart defects, cleft lip/palate (cleft palate and cleft lip), immune system disorders, abnormal facial features and learning problems;
• Wolf-Hirschhorn syndrome(deletion on chromosome 4) - this disorder is characterized by mental retardation, heart defects, poor muscle tone, seizures and other problems. This condition affects approximately 1 in 50,000 babies.

With the exception of people with DiGeorge syndrome, people with the above syndromes are infertile. As for people with DiGeorge syndrome, this pathology is inherited by 50% with each pregnancy.

New methods of chromosome analysis can sometimes pinpoint where genetic material is missing, or where an extra gene is present. If the doctor knows exactly where the culprit is chromosomal abnormality, he can assess the full extent of its influence on the child and give an approximate forecast for the development of this child in the future. Often this helps parents decide to continue the pregnancy and prepare in advance for the birth of a baby that is a little different from everyone else. TAKE THE TEST (15 questions):

CAN YOU BE SINCERELY JOYFUL?

The human body is a complex multifaceted system that functions at various levels. In order for organs and cells to work in the correct mode, certain substances must participate in specific biochemical processes. This requires a solid foundation, that is, the correct transmission of the genetic code. It is the underlying hereditary material that controls the development of the embryo.

However, changes sometimes occur in hereditary information that appear in large groups or affect individual genes. Such errors are called gene mutations. In some cases, this problem relates to the structural units of the cell, that is, to entire chromosomes. Accordingly, in this case the error is called a chromosome mutation.

Each human cell normally contains the same number of chromosomes. They are united by the same genes. The complete set is 23 pairs of chromosomes, but in germ cells there are 2 times fewer of them. This is explained by the fact that during fertilization, the fusion of sperm and egg must represent a complete combination of all the necessary genes. Their distribution does not occur randomly, but in a strictly defined order, and such a linear sequence is absolutely the same for all people.

3 years later, the French scientist J. Lejeune discovered that impaired mental development in people and resistance to infections are directly related to the extra 21 chromosome. She is one of the smallest, but she has a lot of genes. The extra chromosome was observed in 1 in 1000 newborns. This chromosomal disease is by far the most studied and is called Down syndrome.

In the same 1959, it was studied and proven that the presence of an extra X chromosome in men leads to Klinefelter's disease, in which a person suffers from mental retardation and infertility.

However, despite the fact that chromosomal abnormalities have been observed and studied for quite a long time, even modern medicine is not able to treat genetic diseases. But methods for diagnosing such mutations have been quite modernized.

Causes of an extra chromosome

The anomaly is the only reason for the appearance of 47 chromosomes instead of the required 46. Medical experts have proven that the main reason for the appearance of an extra chromosome is the age of the expectant mother. The older the pregnant woman, the more likely nondisjunction of chromosomes. For this reason alone, women are recommended to give birth before the age of 35. If pregnancy occurs after this age, you should undergo an examination.

Factors that contribute to the appearance of an extra chromosome include the level of anomaly that has increased globally, the degree of environmental pollution, and much more.

There is an opinion that an extra chromosome occurs if there were similar cases in the family. This is just a myth: studies have shown that parents whose children suffer from a chromosomal disorder have a completely healthy karyotype.

Diagnosis of a child with a chromosomal abnormality

Recognition of a violation of the number of chromosomes, the so-called aneuploidy screening, reveals a deficiency or excess of chromosomes in the embryo. Pregnant women over 35 years of age are advised to obtain a sample amniotic fluid. If a karyotype disorder is detected, the expectant mother will need to terminate the pregnancy, since the born child will suffer from a serious illness throughout her life in the absence of effective treatment methods.

Chromosome disruption is mainly of maternal origin, so it is necessary to analyze not only the cells of the embryo, but also the substances that are formed during the maturation process. This procedure is called polar body diagnostics of genetic disorders.

Down syndrome

The scientist who first described Mongolism is Daun. An extra chromosome, a gene disease in the presence of which necessarily develops, has been widely studied. In Mongolism, trisomy 21 occurs. That is, a sick person has 47 chromosomes instead of the required 46. The main symptom is developmental delay.

Children who have an extra chromosome experience serious difficulties in mastering material in school, so they need an alternative teaching method. In addition to mental development, there is also a deviation in physical development, namely: slanted eyes, flat face, wide lips, flat tongue, shortened or widened limbs and feet, large accumulation of skin in the neck area. Life expectancy reaches 50 years on average.

Patau syndrome

Trisomy also includes Patau syndrome, in which there are 3 copies of chromosome 13. A distinctive feature is a disruption of the central nervous system or its underdevelopment. Patients have multiple developmental defects, possibly including heart defects. More than 90% of people with Patau syndrome die in the first year of life.

Edwards syndrome

This anomaly, like the previous ones, refers to trisomy. IN in this case We are talking about chromosome 18. characterized by various disorders. Mostly, patients experience bone deformation, an altered shape of the skull, problems with the respiratory system and cardiovascular system. Life expectancy is usually about 3 months, but some babies live up to a year.

Endocrine diseases due to chromosome abnormalities

In addition to the listed chromosomal abnormality syndromes, there are others in which a numerical and structural abnormality is also observed. Such diseases include the following:

1. Triploidy is a rather rare disorder of chromosomes, in which their modal number is 69. Pregnancy usually ends in early miscarriage, but if the child survives, the child lives no more than 5 months, and numerous birth defects are observed.
2. Wolf-Hirschhorn syndrome is also one of the rarest chromosomal abnormalities that develops due to deletion of the distal end of the short arm of the chromosome. The critical region for this disorder is 16.3 on chromosome 4p. Characteristic signs- developmental problems, growth delays, seizures and typical features faces
3. Prader-Willi syndrome is a very rare disease. With such an abnormality of chromosomes, 7 genes or some parts of them on the 15th paternal chromosome do not function or are completely deleted. Signs: scoliosis, strabismus, delayed physical and intellectual development, fatigue.

How to raise a child with a chromosomal disorder?

Raising a child with congenital chromosomal diseases is not easy. In order to make your life easier, you need to follow some rules. First, you must immediately overcome despair and fear. Secondly, there is no need to waste time looking for the culprit, he simply does not exist. Thirdly, it is important to decide what kind of help the child and family need, and then turn to specialists for medical, psychological and pedagogical help.

In the first year of life, diagnosis is extremely important, since motor function develops during this period. With the help of professionals, the child will quickly acquire motor abilities. It is necessary to objectively examine the baby for vision and hearing pathologies. The child should also be observed by a pediatrician, neuropsychiatrist and endocrinologist.

The carrier of an extra chromosome is usually friendly, which makes his upbringing easier, and he also tries, to the best of his ability, to earn the approval of an adult. The level of development of a special child will depend on how persistently they teach him basic skills. Although sick children lag behind the rest, they require a lot of attention. It is always necessary to encourage a child's independence. Self-service skills should be instilled by your own example, and then the result will not be long in coming.

Children with chromosomal diseases are endowed with special talents that need to be discovered. This could be music lessons or drawing. It is important to develop the baby’s speech, play active games that develop motor skills, read, and also teach him routine and neatness. If you show your child all your tenderness, care, attentiveness and affection, he will respond in kind.

Can it be cured?

To date, it is impossible to cure chromosomal diseases; Each proposed method is experimental, and their clinical effectiveness has not been proven. Systematic medical and educational assistance helps to achieve success in development, socialization and acquisition of skills.

A sick child should be observed by specialists at all times, since medicine has reached the level at which it is able to provide the necessary equipment and different kinds therapy. Teachers will use modern approaches to teaching and rehabilitating the child.

Each pregnant woman decides for herself the complex ethical question of whether it is worth conducting an examination to identify genetic pathologies of the unborn baby. In any case, it is important to have all the information about modern diagnostic capabilities.

Yulia SHATOKHA, Candidate of Medical Sciences, Head of the Department of Prenatal Diagnostics, spoke about what invasive and non-invasive methods of prenatal diagnosis exist today, how informative and safe they are and in what cases they are used. ultrasound diagnostics Network of medical centers "Ultrasound Studio".

Why is prenatal diagnosis needed?

Various methods help predict possible genetic pathologies during pregnancy. First of all, this is an ultrasound examination (screening), with which the doctor can notice abnormalities in the development of the fetus.

The second stage of prenatal screening during pregnancy is biochemical screening (blood test). These tests, also known as “double” and “triple” tests, are taken by every pregnant woman today. It allows you to predict with some degree of accuracy the risk of fetal chromosomal abnormalities.

” It is impossible to make an accurate diagnosis based on such an analysis; this requires chromosomal studies - more complex and expensive.

Chromosomal studies are not mandatory for all pregnant women, but there are certain indications:

future parents are close relatives;

expectant mother over 35 years old;

the presence in the family of children with chromosomal pathology;

miscarriages or missed pregnancies in the past;

diseases potentially dangerous to the fetus suffered during pregnancy;

shortly before conception, one of the parents was exposed to ionizing radiation (X-rays, radiation therapy);

risks identified by ultrasound.

Expert opinion

The statistical probability of having a child with a chromosomal disorder is from 0.4 to 0.7%. But it must be borne in mind that this is a risk in the population as a whole; for individual pregnant women it can be extremely high: the basic risk depends on age, nationality and various social parameters. For example, the risk of chromosomal abnormalities in a healthy pregnant woman increases with age. In addition, there is, and then there is an individual risk, which is determined on the basis of biochemical and ultrasound data.

"Double" and "triple" tests

Biochemical screenings also known as , and in common parlance referred to as "test for Down syndrome" or "test for deformities", carried out at strictly defined periods of pregnancy.

Double test

A double test is done at 10-13 weeks of pregnancy. During this blood test, they look at the following indicators:

free hCG (human chorionic gonadotropin),

PAPPA (plasma protein A, inhibitor A).

The analysis should be done only after an ultrasound scan, the data of which is also used when calculating risks.

The specialist will need the following data from the ultrasound report: date of the ultrasound, coccygeal-parietal size (CPR), biparietal size (BPR), nuchal translucency thickness (TN).

Triple test

The second, a “triple” (or “quadruple”) test, is recommended for pregnant women to take at 16-18 weeks.

This test examines the following indicators:

alpha fetoprotein (AFP);

free estriol;

inhibin A (in case of quadruple test)

Based on the analysis of data from the first and second biochemical screening and ultrasound, doctors calculate the likelihood of such chromosomal abnormalities as:

Down syndrome;

Edwards syndrome;

neural tube defects;

Patau syndrome;

Turner syndrome;

Cornelia de Lange syndrome;

Smith Lemli Opitz syndrome;

triploidy.

Expert opinion

A double or triple test is a biochemical test that determines the concentration in the mother’s blood of certain substances that characterize the condition of the fetus.

How are the risks of chromosomal abnormalities calculated?

The results of biochemical screening, in addition to possible chromosomal pathologies, are influenced by many factors, especially age and weight. To determine statistically reliable results, a database was created in which women were divided into groups by age and body weight and the average values ​​of the “double” and “triple” tests were calculated.

The average result for each hormone (MoM) became the basis for determining the normal limit. So, if the result obtained when divided by MoM is 0.5-2.5 units, then the hormone level is considered normal. If less than 0.5 MoM - low, above 2.5 - high.

What level of risk of chromosomal abnormalities is considered high?

In the final conclusion, the risk for each pathology is indicated as a fraction.

A risk of 1:380 and above is considered high.

Average - 1:1000 and below - this is a normal indicator.

A risk of 1:10,000 or less is considered very low.

This figure means that out of 10 thousand pregnant women with such a level, for example, hCG, only one had a child with Down syndrome.

Expert opinion

A risk of 1:100 or higher is an indication for diagnosing chromosomal pathology of the fetus, but each woman determines the degree of criticality of these results for herself. To some, a probability of 1:1000 may seem critical.

Accuracy of biochemical screening in pregnant women

Many pregnant women are wary and skeptical about biochemical screening. And this is not surprising - this test does not provide any accurate information; on its basis, one can only assume the likelihood of the existence of chromosomal abnormalities.

In addition, the information content of biochemical screening may be reduced if:

pregnancy occurred as a result of IVF;

the expectant mother has diabetes mellitus;

multiple pregnancy;

the expectant mother has excess weight or lack thereof

Expert opinion

As an isolated study, double and triple tests have little prognostic value; when taking into account ultrasound data, the reliability increases to 60-70%, and only when conducting genetic tests the result will be 99% accurate. We are talking only about chromosomal abnormalities. If we are talking about a congenital pathology not associated with chromosome defects (for example, “cleft lip” or congenital heart and brain defects), then here reliable result Provide professional ultrasound diagnostics.

Genetic tests for suspected chromosomal abnormalities

Based on the ultrasound conclusion or if the results of biochemical screening are unfavorable, the geneticist may suggest that the expectant mother undergo . Depending on the period, this may be a chorionic villus or placenta biopsy, amniocentesis or cordocentesis. Such a study gives highly accurate results, but in 0.5% of cases such an intervention can cause a miscarriage.

The collection of material for genetic research is carried out under local anesthesia and with ultrasound control. The doctor uses a thin needle to puncture the uterus and carefully remove genetic material. Depending on the stage of pregnancy, this may be particles of chorionic villi or placenta (chorionic or placental biopsy), amniotic fluid (amniocentesis) or blood from the umbilical vein (cordocentesis).

The resulting genetic material is sent for analysis, which will determine or exclude the presence of many chromosomal abnormalities: Down syndrome, Patau syndrome, Edwards syndrome, Turner syndrome (accuracy - 99%) and Klinefelter syndrome (accuracy - 98%).

” Four years ago, an alternative to this method of genetic research appeared - a non-invasive prenatal genetic test. This study does not require obtaining genetic material - it is enough to take blood from the vein of the expectant mother for analysis. The method is based on the analysis of DNA fragments of the fetus, which, during the renewal of its cells, enter the bloodstream of the pregnant woman.

This test can be done starting from the 10th week of pregnancy. It is important to understand that this test is not yet widespread in Russia, very few clinics do it, and not all doctors take its results into account. Therefore, you need to be prepared for the fact that the doctor may strongly recommend an invasive examination in case of high risks based on ultrasound or biochemical screening. Be that as it may, the decision always remains with the future parents.

In our city, non-invasive prenatal genetic tests are performed at the following clinics:

"Avicenna". Panorama test. Non-invasive prenatal genetic diagnosis of aneuploidy 42 t.r. Non-invasive prenatal genetic diagnosis of aneuploidies and microdeletions - 52 rub.

"Almita". Panorama test. Cost from 40 to 54 tr. depending on the completeness of the study.

"Ultrasound studio" Prenetix test. Cost 38 tr.

Expert opinion

Only chromosome analysis can confirm or exclude chromosomal pathology. Ultrasound and biochemical screening can only calculate the magnitude of the risk. Analysis for pathologies such as Down syndrome, Edwards syndrome and Patau syndrome can be carried out from 10 weeks of pregnancy. This is done by obtaining fetal DNA directly from the structures of the fertilized sac (directly invasive method). The risk arising from invasive intervention, in the presence of direct indications, is guaranteed to be lower than the risk of chromosomal pathology (approximately 0.2-0.5% according to various authors).

In addition, today any pregnant woman of her own free will can undergo examination for the presence of major genetic diseases in the fetus using a direct non-invasive method. To do this, you just need to donate blood from a vein. The method is absolutely safe for the fetus, but is quite expensive, which limits its widespread use.

Difficult decision

Each woman decides for herself the question of whether diagnosis of genetic diseases is necessary during pregnancy and what to do with the information obtained as a result of research. It is important to understand that doctors do not have the right to put pressure on a pregnant woman in this matter.

Expert opinion

When the pregnancy is up to 12 weeks, a woman can decide for herself whether to terminate the pregnancy if any pathology of the fetus is detected. At a later date, compelling reasons are needed for this: pathological conditions, incompatible with the life of the fetus and diseases that will subsequently lead to severe disability or death of the newborn. In each specific case, this issue is resolved taking into account the duration of pregnancy and the prognosis for the life and health of the fetus and the pregnant woman herself.

There are two reasons why doctors may recommend terminating a pregnancy:

developmental defects in the fetus that are incompatible with life or with the prognosis of profound disability of the child have been identified;

a condition of the mother in which prolongation of pregnancy can cause an unfavorable course of the disease with a threat to the life of the mother.

Prenatal diagnosis - be it biochemical, ultrasound or genetic testing - is not mandatory. Some parents want to have as much as possible complete information, others prefer to limit themselves to a minimum set of surveys, trusting nature. And every choice is worthy of respect.