Future mother 

Chromosomal abnormalities during pregnancy. Chromosomal pathology - Shereshevsky-Turner syndrome. Types of chromosomal abnormalities

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 laid hereditary material that controls the development of the embryo.

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

Every human cell normally contains the same number of chromosomes. They share the same genes. The complete set is 23 pairs of chromosomes, but in germ cells they are 2 times less. This is because 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.

After 3 years, the French scientist J. Lejeune found that mental disorders in people and resistance to infections are directly related to the extra 21 chromosome. She is one of the smallest, but her genes are concentrated in her. An extra chromosome was observed in 1 out of 1000 newborns. This chromosomal disease is by far the most studied and is called Down syndrome.

In the same 1959, it was studied and proved 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 a long time, even modern medicine unable to treat genetic diseases. But the methods for diagnosing such mutations have been rather modernized.

Causes of an extra chromosome

Anomaly is the only reason for the emergence of 47 chromosomes instead of 46. Specialists in the field of medicine have proven that main reason the appearance of an extra chromosome - the age of the expectant mother. The older the pregnant woman, the more likely nondisjunction of chromosomes. For this reason alone, women are advised to give birth before the age of 35. If you become pregnant after this age, you should be examined.

The factors that contribute to the appearance of an extra chromosome include the level of anomaly, which has increased in the whole world, 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 disease have a perfectly healthy karyotype.

Diagnosis of the appearance of a child with a chromosomal abnormality

Recognition of abnormal number of chromosomes, the so-called screening for aneuploidy, reveals the lack or excess of chromosomes in the embryo. Pregnant women over 35 years of age are advised to undergo a procedure for obtaining a sample of amniotic fluid. If a violation of the karyotype is detected, then the expectant mother will need to terminate the pregnancy, since the born child will suffer all her life serious illness in the absence of effective treatments.

The violation of chromosomes is mainly of maternal origin, therefore, it is necessary to analyze not only the cells of the embryo, but also the substances that are formed during maturation. This procedure is called diagnostics. genetic disorders along the polar bodies.

Down syndrome

The scientist who first described Mongolism is Down. An extra chromosome, the disease of genes in the presence of which necessarily develops, has been widely studied. Mongolism causes trisomy on chromosome 21. That is, in a sick person, instead of the prescribed 46, 47 chromosomes are obtained. The main symptom is developmental delay.

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

Patau Syndrome

Trisomy also includes Patau syndrome, in which there are 3 copies of chromosome 13. hallmark is a violation of the activity of the central nervous system or its underdevelopment. Patients have multiple malformations, including those of the heart. 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 this case, we are talking about chromosome 18. characterized by various disorders. Mostly, patients have bone deformity, an altered shape of the skull, problems with the respiratory system and cardiovascular system. Life expectancy is usually around 3 months, but some babies live up to a year.

Endocrine diseases with chromosomal abnormalities

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

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

How to raise a child with a chromosomal disease?

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 should 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 and psychological and pedagogical help.

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

The carrier of the extra chromosome is usually friendly, which makes it easier to raise him, and he also tries to earn the approval of an adult to the best of his ability. The level of development of a special baby will depend on how hard they teach him basic skills. Sick children, although lagging behind the rest, require a lot of attention. It is always necessary to encourage the independence of the child. You should instill self-service skills 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 developed. It could be music or painting. It is important to develop the baby's speech, play active and motor skills games, read, and also accustom to the regime and accuracy. If you show all your tenderness, care, attentiveness and affection to the child, he will answer the same.

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 pedagogical assistance helps to achieve success in development, socialization and the acquisition of skills.

A sick child should be observed by specialists all the time, since medicine has reached the level at which it is able to provide the necessary equipment and different kinds therapy. The teachers will apply modern approaches in the education and rehabilitation of the child.

What are chromosomal abnormalities?

It is a type of genetic condition caused by major changes in the genetic material. Most cases occur in children with multiple birth defects or complex problems that develop from birth.

What are chromosomes?

Chromosomes are structural formations in all cells of the human body that store genetic information, large elements of deoxyribonucleic acid (DNA). A normal human has forty-six chromosomes.

What features of appearance force us to suspect the presence of chromosomal abnormalities of the fetus?

These features can be as serious as missing eyes or heart abnormalities, or less significant. wrong position ears or short fingers. The specific features of chromosomal developmental anomalies depend on which particular chromosome is involved.

How does this pathology develop?

In most cases, chromosomal abnormalities of pregnancy occur at the time of the formation of an egg or sperm. Sometimes chromosomal changes occur shortly after conception during the initial stages of embryonic development. In rare cases, a chromosomal abnormality in children is inherited from one of the parents. In this case, the parent either has or does not have a similar problem.

What studies are needed for an accurate diagnosis?

The most common test is an analysis for the presence of chromosomal abnormalities, or karyotype. It is carried out using a blood sample, which is sent to a cytogenetics laboratory (chromosomes are examined in it). The laboratory processes the sample, photographs the chromosomes, counts them and examines them closely. Laboratory workers look for significant changes in chromosomes, such as a missing or extra element. But given test does not reveal small changes in the genetic material. Chromosomal analysis for the presence of anomalies takes from ten days to two weeks.

Fluorescent in situ hybridization - the FISH method (appointed depending on the specific characteristics of the child) allows you to explore small elements of genetic material, as well as new method- analysis of DNA microarrays (in some cases it is preferable to a FISH test).

What kind of complications can result from chromosomal abnormalities?

If a child has a physical anomaly, such as the absence of a hand or foot, all complications will be associated with it. Most of the diseases associated with chromosomal abnormalities entail mental retardation, which can be very significant. Serious chromosomal abnormalities associated with strong changes in genetic material lead to death in infancy or childhood.

Are chromosomal abnormalities treatable?

The risks of chromosomal abnormalities are not treatable. There is no way to extract an abnormal chromosome and put a normal one in its place. However, your child will be provided with the necessary treatment. The specific type of treatment (physiotherapy, heart surgery) is determined based on the needs of your baby.

Is it possible to have our next child with the same pathology?

If a child has a disease due to a chromosomal abnormality, both parents are usually examined. If both have a normal chromosome set, the risk of having another child with a pathology is not higher than usual. (There is always a risk.) If one of the parents has a chromosomal abnormality, the chance of having a child with the abnormality is at least fifty-fifty. Depending on the specific chromosomal abnormality, the chance of developing a pathology in the next child may be two out of three.

Should we seek advice from a geneticist or other specialist?

Yes. Your child should be seen by a doctor who specializes in genetics. He will help you organize the examination and tell you what to expect from a child with a chromosome disorder. With him, you can discuss the likelihood of developing a similar pathology in the next child, markers of chromosomal abnormalities and get contact information for other families where there are children with the same problems.

What special care regimen should we follow when we return home?

Your child with a chromosome disorder will need traditional pediatric care. If he needs special care, such as tube feeding, you should be taught him at the hospital. In some cases, children with chromosomal abnormalities do not live very long. You may decide to enroll your child in hospice. Hospice programs support both the child and the parents in order to provide the family with the proper quality of life, even if the baby does not live long.

When is it worth re-showing the child to the doctor in connection with the disease and the presence of a chromosomal abnormality?

It is likely that your child will have frequent check-ups with different doctors and physical therapy. He may need an operation. Your pediatrician will help arrange visits to all doctors.

Angela Scheuerli, MD, geneticist.

A difficult ethical question, whether it is worth conducting an examination to identify genetic pathologies of the unborn baby, each pregnant woman decides for herself. In any case, it is important to have all the information about modern possibilities diagnostics.

About what invasive and non-invasive methods of prenatal diagnostics exist today, how informative and safe they are, and in what cases they are used, said Yulia SHATOKHA, Ph.D. ultrasound diagnostics networks medical centers"Ultrasound Studio"

Why is prenatal diagnosis needed?

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

Second phase prenatal screening during pregnancy - biochemical screening (blood test). These tests, also known as "double" and "triple" tests, are now carried out by every pregnant woman. It allows, with some degree of accuracy, to predict the risk of the existence 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 required for all pregnant women, but there are certain indications:

    future parents are close relatives;

    future mother over 35 years old;

    the presence in the family of children with a chromosomal pathology;

    miscarriages or missed pregnancies in the past;

    diseases potentially dangerous to the fetus during pregnancy;

    shortly before conception, one of the parents was exposed to ionizing radiation (X-ray, 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 keep 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 there is an individual risk, which is determined on the basis of data from biochemical and ultrasound studies.

"Double" and "triple" tests

Biochemical screenings also known as , and colloquially referred to at all Down Syndrome Analysis or "deformity analysis", carried out in strict certain deadlines pregnancy.

double test

A double test is done at 10-13 weeks of pregnancy. During this blood test, the value of such indicators as:

    free hCG (human chorionic gonadotropin),

    PAPPA (plasma protein A, inhibitor A).

The analysis should be done only after ultrasound, the data of which are also used in the calculation of risks.

The specialist will need the following data from the ultrasound report: date of ultrasound, coccygeal-parietal size (KTR), biparietal size (BDP), thickness collar space(TVP).

triple test

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

During this test, the number of the following indicators is examined:

    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

Double or triple test it biochemical analyzes, which determine the concentration in the mother's blood of certain substances that characterize the condition of the fetus.

How is the risk 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 the statistically significant results, a database was created in which women were divided into groups by age and body weight and the averages of the “double” and “triple” tests were calculated.

The average result for each hormone (MoM) became the basis for determining the limit of the norm. So, if the result obtained when dividing 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 degree of risk of chromosomal abnormalities is considered high?

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

    The 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 has a child with Down syndrome.

Expert opinion

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

Accuracy of biochemical screening of 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, based on it, one can only assume the probability of the existence chromosomal disorders.

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

    pregnancy occurred as a result of IVF;

    with the expectant mother diabetes;

    multiple pregnancy;

    future 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 genetic analyzes are performed, the result will be 99% accurate. We are talking only about chromosomal disorders. If we're talking about congenital pathology not associated with chromosomal defects (for example, cleft lip or congenital malformations of the heart and brain), then professional ultrasound diagnostics will give a reliable result.

Genetic tests for suspected chromosomal abnormalities

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

The sampling of material for genetic research is carried out under local anesthesia and with ultrasound control. With a thin needle, the doctor makes a puncture of the uterus and carefully takes the genetic material. Depending on the gestational age, these may be chorionic or placental villus particles (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, Evards 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 for him to take blood from the vein of the expectant mother for analysis. The method is based on the analysis of fetal DNA fragments, which, in the process of renewing its cells, enter the pregnant woman's bloodstream.

You can do this test from the 10th week of pregnancy. It is important to understand that this test is still not widely used in Russia, very few clinics do it, and not all doctors take into account its results. Therefore, you need to be prepared for the fact that the doctor may strongly recommend an invasive examination in case of high risks by 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 by clinics:

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

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

    "Ultrasound Studio". Prenetix test. Cost 38 tr.

Expert opinion

Only chromosomal analysis can confirm or rule out a chromosomal pathology. Ultrasound and biochemical screening can only calculate the magnitude of the risk. Analysis for pathologies such as Down syndrome, Edwards and Patau can be carried out from 10 weeks of pregnancy. This is done by obtaining fetal DNA directly from the structures gestational sac(straight 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 different authors).

In addition, today any pregnant woman own will can be screened for underlying genetic diseases in the fetus by a direct non-invasive method. To do this, it is enough just to donate blood from a vein. The method is absolutely safe for the fetus, but quite expensive, which limits its widespread use.

Tough decision

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

Expert opinion

With a gestational age of up to 12 weeks, a woman herself can decide on the need to terminate the pregnancy if any pathology of the fetus is detected. In more late dates for this, good reasons are needed: pathological conditions incompatible with the life of the fetus and diseases that will subsequently lead to profound disability or death of the newborn. In each 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:

    fetal malformations that are incompatible with life or with the prognosis of a deep disability of the child have been identified;

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

Prenatal diagnosis - whether biochemical, ultrasound or genetic research, is optional. Some parents want to have the most complete information, others prefer to be limited minimum set surveys, trusting nature. And every choice is worthy of respect.

Before you is a unique book that reveals the causes of a missed pregnancy - the most actual problem future mothers. After reading it, you will learn about the most common causes of fetal death in the early stages: chromosomal abnormalities, infections, hereditary thrombophilia and many others. The author, Ph.D., will tell you how to prevent these diseases and get a chance to have a baby. In the book, you will also get acquainted with the ancient Chinese secrets of conception and pregnancy, which will help you overcome fear on the path of motherhood.

Chromosomal abnormalities fetus

most common cause abortion is hereditary pathology at the fetus. More often these are some kind of chromosomal abnormalities, as a rule, incompatible with the life of the fetus and leading to spontaneous miscarriage or the birth of children with malformations.

More often, embryos with an incorrect karyotype (set of chromosomes) die in the first weeks of pregnancy. So, in the first 6-7 weeks of pregnancy, the majority (60-75%) of dead fetuses have an incorrect karyotype, at 12-17 weeks - a quarter (20-25%), 17-28 weeks - only 2-7%. We will talk in detail about the types of chromosomal abnormalities (HA) that prevent the preservation of pregnancy in this section. Let's start with the basics of genetics.

Secrets of DNA

All information about the structure of our body, predisposition to diseases, as well as age-related changes and longevity is found in DNA (deoxyribonucleic acid) molecules. It provides storage, transmission from generation to generation and implementation of the genetic program for the development and functioning of the body, the structure of proteins from which the body is built.

DNA is located in the nucleus of the cell as part of the chromosomes. Each person has 46 paired chromosomes (Figure 4): we get the first set (22 chromosomes) from one parent, the second from the other. 44 out of 46 chromosomes do not depend on sex, and two determine it: XY - in men or XX - in women.

Figure 4. Human chromosome set

From a chemical point of view, DNA consists of repeating nucleotide blocks that form two chains of ribonucleic acid (RNA) twisted together in the form of a spiral (Fig. 5). Therefore, the structure of the DNA molecule is called " double helix". DNA is the body's genetic library, found in every cell. In total, each person has 120 billion miles of DNA.

Figure 5. DNA replication

There are four types of nitrogenous bases found in DNA (adenine, guanine, thymine, and cytosine). Their sequence allows you to "encode" information about the structure of the whole organism. Chromosomes in total contain approximately 3 billion base pairs of DNA nucleotides, forming 20,000-25,000 genes.

Cell reproduction occurs through DNA replication (Fig. 5). At the same time, it unwinds into two strands of RNA (a). They diverge and form a replication fork (b). Then each RNA becomes a template on which a similar chain is completed (c). As a result, two new double-stranded DNA molecules (d) are formed, identical to the parent molecule.

Similarly, protein synthesis occurs in cells: DNA unwinds; information is read from it by the method of completing the construction of RNA, which leaves the nucleus for ribosomes (cell structures), where it becomes a matrix for protein synthesis; the untwisted DNA is twisted again into a spiral.

Fundamentals of genetics

Genes are carriers of human hereditary information. Each gene is a section of the DNA molecule that carries information about a particular protein. A complete set of human genes (genotype) is responsible for the functioning of the body, its growth and development. The combination of many genes determines the uniqueness of each person.

Genes are passed on to a child from parents: one “set” is from mom, the other is from dad. That is why children look so much like their parents.

If from both parents we got the same genes responsible for any trait, for example, blue eyes, then the genotype is considered homozygous for this trait, and the eye color will be blue (Figure 6 a).

If we inherited different genes (for example, from the mother - blue eyes, from the father - dark), then the genotype is considered heterozygous (Figure 6 b). In this case, the sign that is dominant (predominant) appears, and the color of the eyes will be dark.

Genes in different people are similar, but there are slight differences - polymorphisms. Significant changes in genes that lead to disruption of cell function are called mutations (abberations). In a living cell, genes are constantly mutating. The main processes during which failures occur are DNA replication and transcription.

Some changes (polymorphisms or mutations) lead to intrauterine death of the fetus, others become the causes of gene diseases and appear immediately after birth, and others are a factor that only predisposes to the occurrence of certain diseases.

Figure 6. Homozygous (a) and heterozygous (b) types

Types of chromosomal disorders

There are two main types of chromosomal disorders (mutations, aberrations):

1. Quantitative changes in the number of chromosomes (aneuploidy): the presence of an extra chromosome (trisomy) or the absence of one of the two paired chromosomes (monosomy). They occur when there is a violation of the divergence of chromosomes in the process of cell division, as a result of which the genetic material is unevenly distributed among the daughter cells. Aneuploidy leads to miscarriages or the formation of malformations.

The most common trisomy is on the 16th chromosome, the result of which is an early spontaneous miscarriage. Carriers of trisomy on chromosomes 13 (Patau syndrome) and 18 (Edwards syndrome) can survive until birth, but are characterized by significant developmental disorders, and therefore more often die immediately after birth.

The only type of trisomy on autosomal (non-sex) chromosomes, in the presence of which the birth of a viable child is possible, is Down syndrome (trisomy on chromosome 21). I will talk about this pathology in detail in the corresponding chapter.

Also described are chromosomal abnormalities in which the number of sex chromosomes increases. The most common are: Shereshevsky-Turner syndrome (we will talk about it separately); Klinefelter's syndrome (47XXY instead of 46XY), in which the birth of a male baby is possible, endowed with some secondary female sexual characteristics, and others.

If there is an additional set of chromosomes in the cell, polyploidy is formed. For example, when one egg is fertilized by two sperm at once, triploidy (a triple set of chromosomes) occurs.

2. You may also experience disorders in the structure of chromosomes: deletion (loss of part), inversion (rotation of a chromosome section by 180̊), ring (chromosome forms a ring structure), duplication (repetition of a chromosome section), translocation (transfer of a chromosome part to another).

With balanced structural disorders of chromosomes, the amount of chromosomal material presented corresponds to the norm, only their configuration is changed. A person with structural aberrations of chromosomes, as a rule, has no manifestations, except possible problems with the reproduction of healthy offspring. Chromosomal abnormalities can be passed from parent to child.

Down syndrome

In the mechanism of the occurrence of Down's syndrome lies a violation of the divergence of chromosomes during the maturation of germ cells (gametes).

During this process, in both men and women, a normal somatic cell divides, containing a double (diploid) set of chromosomes, into two daughter cells with a halved number of chromosomes (Fig. 7). If the number of chromosomes in gametes remained diploid, as in somatic cells, then it would double during fertilization in each generation.

Figure 7. Maturation of germ cells from the somatic

In violation of the divergence of chromosomes, gametes with the wrong number of them mature. If such a "pathological" sex cell is involved in fertilization, then there is a high risk of conceiving a child with a hereditary pathology.

In the presence of an additional 21st chromosome, Down syndrome is formed (Fig. 8). This is one of the forms of genomic pathology, in which the karyotype is represented by 47 chromosomes (trisomy on chromosome 21) instead of 46, that is, from one of the parents (carrier of the disease), the child got not one 21st chromosome, as expected, but two; the third he received from another (healthy) parent.

A change in the number of chromosomes is often incompatible with life and leads to the death of the embryo, which is one of the main causes of miscarriage in the first trimester. However, a fetus with Down syndrome does not always die. Often, such children are still born - on average, there is one case in 700 births.

Figure 8. Trisomy on chromosome 21. Down syndrome

Down syndrome is a severe disorder characterized by dementia, developmental delay, and other birth defects. At the moment, thanks to prenatal diagnosis, the frequency of birth of children suffering from this pathology has decreased to 1 in 1100.

Children with Down Syndrome may be genetically healthy parents. However, the likelihood of conceiving such a child increases with age. If a woman is over 45 years old, then the risk is 1:19. There is also an increase in the incidence of this syndrome in a child whose father is older than 42 years.

Shereshevsky-Turner syndrome

One of the reasons for abortion is genetic disease fetus, like Shereshevsky-Turner syndrome. This is a chromosomal pathology characterized by the presence of monosomy on the X chromosome (one X chromosome instead of two).

Pregnancy in the presence of such a syndrome in the fetus most often (in 98%) ends in spontaneous miscarriage in the early stages. If this did not happen, and a girl with Shereshevsky-Turner syndrome was born, she will lag behind in physical development. Typical signs of the syndrome are: short stature, barrel-shaped rib cage, short neck. In this case, the intellect most often does not suffer.

due to defect or total absence of one sexual X-chromosome, the formation of the gonads is disrupted: the ovaries may be completely absent, the uterus may be in its infancy.

Since the ovaries do not usually exist in this pathology, estrogens are not produced. As a result, the level of gonadotropins rises and amenorrhea (absence of menstruation) is noted.

The main type of treatment for patients with Shereshevsky-Turner syndrome is hormonal therapy, which begins at the age of 14–16. This leads to the feminization of the physique, the development of female secondary sexual characteristics, and reduces the increased activity of the hypothalamic-pituitary system. Therapy is carried out during the entire childbearing age of patients. However, women with Shereshevsky–Turner syndrome are infertile due to the absence of ovaries.

How often is pregnancy terminated due to chromosomal abnormalities?

Chromosomal aberrations are the most common cause of miscarriage: 50 to 95% of miscarriages are due to chromosomal abnormalities in the fetus. With a missed pregnancy, among chromosomal abnormalities, the following are more often detected:

-45-55% - autosomal trisomies,

-20-30% - monosomy,

-15-20% - triploidy.

Parents of a fetus with an increased number of chromosomes are most often healthy, and analysis of their karyotype is not very informative. The risk of recurrence of quantitative chromosomal aberrations (eg, trisomy) in subsequent pregnancies is about 1%, which will require prenatal diagnosis in the first trimester. The couple should be informed about this in case of fetal death and detection of CA.

If structural aberrations of chromosomes are detected in the fetus, karyotyping in parents is mandatory, since in families where one of the parents has a violation of the chromosome structure (for example, translocation), the risk of spontaneous abortion increases to 25% -50%.

In some cases, with structural aberrations of fetal chromosomes, pregnancy can progress, and a child with significant malformations will be born. Probability of being born healthy baby persists in parents with structural chromosome aberrations. But in 1-15% of cases, it will have genetic abnormalities.

As we have already said, an important role in establishing the cause of spontaneous miscarriage is played by a cytogenetic study of abortion material.

Visiting a geneticist

A visit to a geneticist can help determine the cause of a miscarriage.

Question: Tell me what should I do? I could not get pregnant for 4 years, then I succeeded. But at 6 weeks, an ultrasound scan said that there was a threat of miscarriage. Then everything was fine, and at 12 weeks they started bleeding. They did a second ultrasound, they said that the fetus froze in development at 9 weeks. Please tell me what treatment to get and can I still get pregnant? Thank you.

Question: I had a scraping once, the second time medical abortion, since both pregnancies were frozen. Has handed over analyzes on the latent infections, result negative. There were no births, I really want a baby. Tell me, please, what other tests do I need to take?

It is the chromosomal pathology of the fetus that leads to its intrauterine death in the early stages of development (the so-called “missed pregnancy”) and spontaneous miscarriage. Therefore, if you have had miscarriages or miscarriages in the past, you should undergo a genetic examination.

Often, expectant mothers are very wary of medical genetic counseling. And in vain! This study allows you to pre-determine the degree of risk of having children with genetic abnormalities.

Such disorders in the fetus can be inherited from one of the parents or be caused by adverse external influences: smoking of the expectant mother, drinking alcohol, taking certain drugs, past infections exposure to radiation during and before conception.

Consultation with a specialist is necessary if:

– future parents or their relatives have any hereditary diseases;

- there is a child with a genetic pathology in the family;

- future parents are relatives;

- the age of the future mother is over 35 years old, the father is over 40 years old;

– previous pregnancies were frozen or ended in spontaneous miscarriages;

– the parents-to-be have been exposed to radiation or for a long time worked with harmful chemicals;

future mom took strong medications during conception and/or early pregnancy.

Couples at risk should undergo medical genetic examination V without fail. If desired, any couple planning a child can consult a geneticist.

After the onset of pregnancy, special control is established for women at risk. At 10-13 weeks of pregnancy, it is necessary to conduct a prenatal diagnosis of the baby's health, which we will discuss later.

First trimester screening

A set of measures aimed at early detection of pathology in the fetus is called prenatal diagnosis. According to the latest order of the Ministry of Health and SR No. 808 dated 02.10.2009, the screening of the first trimester, which is carried out at 11-14 weeks of pregnancy, includes the following studies:

1. Ultrasound of the fetus with an assessment:

- the thickness of the collar space (TVP); this is the area between inner surface skin of the fetus and the outer surface of its soft tissues covering cervical region spine, in which fluid can accumulate; normally, in terms of 11-14 weeks, TVP is 2-2.8 mm; is a marker of fetal chromosomal disorders, primarily Down syndrome;

– the presence and length of the nasal bone (NK); normal for a period of 12-13 weeks is 3 mm; its absence is suspicious of Down syndrome.

2. Maternal serum markers (" double test»):

– free human chorionic gonadotropin (b-hCG); normally for a period of 12 weeks, its level is 13.4-128.5 ng / ml; 13 weeks - 14.2-114.7 ng / ml; 14 weeks - 8.9-79.4 ng / ml; allows you to determine the risk of developing some trisomies: Down syndrome (chromosome 21), Edwards syndrome (18) and Patau syndrome (13);

- pregnancy-associated plasma protein A (PAPP-A): normal for a period of 11-12 weeks is 0.79-4.76 mU / l, 12-13 weeks - 1.03-6.01 mU / l; 13-14 weeks - 1.47-8.54 mU / l; with Down and Edwards syndrome, its level is reduced.

Question: I am 34 years old. At week 12, I passed a “double test”: PAPP-A is normal - 3.07, and hCG - more than normal(178.0). Ultrasound showed no pathology. Is there a reason for concern? Is it possible to leave the pregnancy?

The discrepancy between the results of the first trimester screening does not indicate the need for an immediate termination of pregnancy, but only signals possible risk, which after passing the examination is calculated individually for each patient.

If a pathology is suspected in the fetus, according to the screening data, the question of conducting an in-depth (invasive) examination is raised. The most reliable way to make a diagnosis is to study the chromosomal set of fetal cells. For this purpose, study amniotic fluid(perform amniocentesis), placental tissues (placentocentesis), chorionic villi (biopsy), fetal cord blood (cordocentesis).

Comment from the forum : I am 38 years old. I registered for pregnancy only at 11 weeks. At the first screening at 12 weeks, the ultrasound doctor measured the thickness of the collar space of 2.9 mm, and hCG was also elevated. They sent me to a geneticist, and it turned out that it could be an indicator of Down's syndrome. They offered to do an amniocentesis at 18 weeks to determine exactly if there was a syndrome or not, but I refused. Until the last, I hoped that the doctor was mistaken, the measure was not accurate. But at 21 weeks at the second screening, the same doctor found a complex inoperable heart disease and kidney pathology in the child. As they explained to me, these are also signs of Down syndrome. The Commission decided to call artificial childbirth. It's a pity that I didn't trust doctors sooner. So the first screening is a good thing!

At high risk chromosomal abnormalities in the fetus, a woman is offered an additional invasive examination (amniocentesis, cordocentesis) in order to obtain fetal cells and study their chromosome set.

As we have said, invasive procedures are fraught with a number of complications. Therefore, I quite often encounter the fact that the results of biochemical screening cause a lot of worries and questions in women.

History from practice: I have a young patient, Irina, with thrombophilia. Once, after passing the first screening, she wrote me a letter: “Olga, Good evening. I did an ultrasound and everything is fine. And then the transcript of biochemical screening came, and I was shocked by it ... Can I send you the results?

The analysis determined a low level of PAPP-A. The computer calculated the likely risk of developing Down syndrome in a child: >1:50.

Irina was very worried, because this is her long-awaited pregnancy after two miscarriages. Is it Down now? I explained to my patient that PAPP-A is reduced not only due to fetal chromosomal pathology, but also for other reasons. First of all, a low level of PAPP-A may indicate a threat of abortion.

Irina remembered that in the last pregnancy before the miscarriage, the value of PAPP-A was also low. Therefore, we decided to focus on drugs that prevent the occurrence of fetal-placental insufficiency. In addition, I prescribed a second course of low molecular weight heparin, which thins the blood.

The girl calmed down. A few weeks later, she underwent a second ultrasound screening, according to which the fetus developed normally. She sent me the perfect results of the ultrasound and wrote that there was my merit in achieving them)

But for those women who, having received the results of the first screening, are worried about increased risk development of chromosomal abnormalities in the fetus, I recommend that, without waiting for the second screening ultrasound, to undergo a simple examination (Irina, unfortunately, it was not possible to do it).

Non-invasive prenatal test

An alternative to biochemical screening and invasive procedures during pregnancy (chorionic villus biopsy, amniocentesis) today is a non-invasive prenatal test (NIPT). It is carried out using the usual venous blood sampling from the expectant mother.

5-10% of the fetal DNA circulates in the mother's blood. NIPT makes it possible to isolate fetal DNA from the blood of a pregnant woman and analyze it using the latest technology.

NIPT is used in many countries around the world: USA, UK, Spain, Germany, France, Italy, Brazil, South Korea, Singapore, Chile, etc. Disadvantages: The test is not available everywhere and is expensive.

Modern diagnostic technologies make it possible to detect any deviation in the development of the fetus from the very early stages of pregnancy. The main thing is to pass all the necessary examinations in a timely manner and follow the recommendations of specialists.

Second trimester screening

The tactics of prenatal diagnosis in the second trimester has changed significantly in last years. It is important to know this for expectant mothers with suspected chromosomal pathology in the fetus.

So, according to an earlier order of the Ministry of Health of Russia No. 457 of December 28, 2000, second trimester screening was to include three ultrasound scans at 22-24 weeks of gestation and an assessment of biochemical markers of fetal malformations at 16-20 weeks (the so-called "triple test" ): alpha-fetoprotein (AFP), chorionic gonadotropin human (hCG) and estriol (E 3).

The "triple test" was designed to detect fetal malformations, primarily Down syndrome. However, studies conducted over the next 9 years showed that the prenatal diagnosis scheme approved by Order No. 457 does not reduce the frequency of birth of babies with congenital defects, for example, Down syndrome. The incidence of children and their mortality, including intrauterine, remained high, despite the work of antenatal clinics by order of the Ministry of Health of the Russian Federation No. 457. These data are confirmed by comments from the forums:

Comments from the forum:

-Yes, I would only do the first screening, if it is in order, then everything will be fine! And further screenings are not needed! Even if they show something “wrong”, is it really possible to have an abortion at such a time? And suddenly he will be completely healthy! So you won’t forgive yourself for this all your life!

- I did screening twice: the first was normal, the second showed an increased (1:32) risk of Down syndrome! According to the ultrasound, everything was in order, but the doctor recommended an amniocentesis just in case. No pathology was identified. A healthy girl was born!!! So I didn’t understand why I did the second screening and amniocentesis? It is a pity that there are very few good thoughtful specialists.

– Personally, I was very disappointed in the second screening. On the first I was all right, and on the second - found elevated hCG. My doctor told me that this is a fetal pathology. Imagine what happened to me!? I shed so many tears! Pregnant women don't have to worry! The doctor recommended me to visit a geneticist, but I spat on all the doctors and thought: come what may, because the first screening did not reveal anything! I gave birth to a completely healthy baby to everyone's joy! And now I think, why did they come up with this stupid second screening? To wag the nerves of pregnant women?

Due to the low level of information old scheme prenatal diagnosis, it was decided to change it. And in 2009 came out new order No. 808n, according to which biochemical screening of the second trimester was EXCLUDED from the scheme of prenatal diagnosis!

No more "triple test". It is not necessary to conduct it due to the low information content and a large percentage of subsequent unreasonable invasive interventions.

However, some women's consultations in our country, they do not have the necessary information about changes in the procedure for examining pregnant women with suspected chromosomal abnormalities and continue to prescribe a “triple test”. I repeat: do not do this now!

In addition, according to the new order No. 808 of 2009, the time for ultrasound of the second trimester has been shifted from a point of 22-24 weeks to more early dates(20-22), so that in case of detection of abnormalities in the fetus, the woman has the opportunity to terminate the pregnancy until the 24th week, that is, until the time when the fetus is considered viable. The next ultrasound is recommended to be performed at 32-34 weeks of pregnancy.

Ultrasound signs of Down's syndrome in the second trimester are: violation of the formation of bones of the skeleton, expansion of the collar space, the presence of heart defects, expansion of the renal pelvis, cysts of the choroid plexus of the brain. If they are detected, a decision can be made to conduct invasive techniques for the diagnosis of Down syndrome and other chromosomal abnormalities.

But this is not all the innovations in the field of prenatal diagnostics carried out in our country. At present, Russia is approaching world standards in this direction. Don't believe? I'll tell you about it in detail.

International standard for prenatal diagnosis FMF

In Europe, in recent years, a new branch has appeared - "fetal medicine", which deals with the health of the baby in the womb. Prenatal diagnostics physicians are trained and certified by the Fetal Medicine Foundation (FMF) program, led by Professor Kypros Nikolaides.

FMF is engaged in research in the field of fetal medicine, diagnosis of fetal anomalies, detection and treatment various complications pregnancy, and also provides training and certification of specialists in all types of ultrasound examinations during pregnancy. The purpose of the FMF is to organize, implement and control the quality of a standardized examination of pregnant women in the first trimester (11-14 weeks) of pregnancy.

According to international standard The FMF examination at this time should include:

– Qualified ultrasound of the fetus between 11 and 14 weeks;

– determination of biochemical parameters of hCG and PAPP-A.

The standardized FMF examination in the first trimester provides for both theoretical and practical training of doctors conducting ultrasound, as well as further verification of the quality of the studies. At the same time, a standardized study of maternal blood is carried out with a guarantee High Quality work.

certification process and educational material in the FMF courses, it is brought into line with generally accepted German requirements. Participants who pass the theoretical and practical examinations are certified through the FMF-Deutschland society, registered as ultrasound specialists and entered on the Internet pages of both FMF-Deutschland and FMF UK.

A certificate for ultrasound examination at 11-14 weeks of gestation can only be issued personally to a certified person. Today, hundreds of domestic ultrasound specialists have received the FMF certificate.

Certified physicians and centers receive FMF-developed software to calculate the risk of fetal chromosomal abnormalities from ultrasound and biochemical screening.

National project "Health"

In Russia at the beginning of this century, the level of prenatal diagnostics lagged far behind Europe due to the low level of training of ultrasound doctors.

Chromosomal pathology is a violation in the structure, structure of chromosomes, a change in the number of chromosomes. Chromosomal pathology is a number of hereditary diseases caused by various genomic mutations, structural changes chromosomes.

Study of chromosomal pathology

Chromosomal pathology is a violation in the structure and structure of chromosomes, which leads to the development of defects, hereditary diseases. The study of chromosomal pathology is offered to everyone, who is at risk:

  • Women who are planning a pregnancy over the age of 35.
  • Women who have had a spontaneous abortion.
  • Women with a history of stillborn children.
  • Spouses who have close relatives with hereditary diseases.
  • Other reasons.

Chromosomal abnormalities during pregnancy

Pregnant women undergo the first test for the presence of chromosomal pathology from 9 to 13 weeks. The second stage of perinatal biochemical screening takes place at 16 to 18 weeks of gestation. Chromosomal pathologies during pregnancy are not often found, but they can lead to missed pregnancy, premature birth, spontaneous miscarriage. If a chromosomal pathology is detected in time during pregnancy, a woman has the right to decide what to do next - give birth to a sick child or terminate the pregnancy.

Analysis for chromosomal abnormalities of the fetus

An analysis for fetal chromosomal pathologies is a study of biochemical markers that is performed in the first trimester of pregnancy. In a pregnant woman, the placenta and fetus secrete substances that enter the mother's blood. An analysis for fetal chromosomal pathologies allows you to determine the concentration of these substances in the mother's blood. Blood for chromosomal pathology is taken from a vein.

Chromosomal studies of the fetus

Chromosomal studies of the fetus are a chorionic biopsy and amniocentosis. Chromosomal studies of the fetus of this species are carried out if the analysis for chromosomal abnormalities of the fetus showed abnormalities. Amniocentosis is a puncture of the amniotic membrane, during which amniotic fluid is taken for laboratory research. A chorionic biopsy is the collection of a tissue sample from the placenta (chorionic villi). These chromosomal studies of the fetus help diagnose many chromosomal pathologies.

Children with chromosomal abnormalities

Children with chromosomal pathology have certain external signs. Down syndrome is characterized by oblique palpebral fissures, a flat nose bridge, and a flat facial profile. A flat facial profile occurs in almost 90% of children with Down syndrome, a flat bridge of the nose occurs in 65% of affected children. Children with a chromosomal pathology, Down syndrome, have distinctive features- open mouth, slightly protruding tongue, epicanthus, characteristic low hair growth on the back of the head, also on the back of the head excess skin. These signs of pathology are found in 80% of cases of Down syndrome, in 60% of cases dysplastic ears, short fingers, and a narrow palate are noted. In a child with Down syndrome, the shape of the teeth changes - they take on the appearance of sharp fangs, changes appearance language - the language resembles a geographical relief, it is given the name - "geographical language". Down syndrome is accompanied by many developmental disorders - mental retardation, muscle hypotension, which occurs in 80% of cases of pathology. The pathology of heart development in Down syndrome is detected on average in 50% of sick children. Children with chromosomal pathology Down syndrome have reduced immunity.

Chromosomal pathology Down syndrome has several forms:

  • A simple form is chromosomal pathology Down syndrome, chromosome 47.XX. 21+. Chromosomal pathology of a simple form is common - in 95% of cases of Down syndrome.
  • Mosaic form - chromosomal pathology Down syndrome, chromosome 47.XY.21+/46. XY, is rare, in 1% of cases of pathology.
  • Translocation form - chromosomal pathology Down syndrome, chromosome 47.XX.t 21|15; as well as 47.XY/t 21/21, occurs in approximately 4% of cases of this pathology. In the case of a Robertsonian translocation, it is possible for carriers of the genetic translocation to give birth to a child with Down syndrome:
  • 45.ХХ.t 21/15 (mother) - from 10 to 15%.
  • 45.XY.t 21/15 (father) - from 5 to 7%.
  • 45.ХY.t 21/21 (either parent) – 100%.

Children with Down syndrome must undergo central nervous system stimulation - specific and non-specific, surgery if it is shown. Children with Down syndrome tend to be very obedient and dutiful. With the right upbringing, they can take care of themselves, take care of pets, read well, sing, and completely repeat the actions of an adult while doing work. Children with chromosomal pathology should undergo social rehabilitation for adaptation in society, special training, upon reaching certain age- Affordable employment.

Chromosomal pathology - Y chromosome disomy syndrome

Y chromosome disomy syndrome was described relatively recently - in 1961. Y chromosome disomy syndrome is a 47. XYY karyotype, rare - one newborn baby per 1000. Children with Y chromosome disomy do not differ from their peers, most often they are taller than average. In adult men, the average height is about 186 cm. There are practically no differences with healthy people in sexual, mental and physical development, most men have normal hormonal status and fertility. In 35% of cases of pathology, there are signs characteristic of the disease: protruding superciliary ridges and bridge of the nose, rough facial features, large lower jaw, large auricles, teeth have defects in the enamel covering them, deformation of the knee and elbow joints is very common. The disease is characterized by increased suggestibility of the patient, imitation, children with this syndrome quickly grasp the negative forms of behavior of their peers. Such patients are characterized by aggressive behavior, impulsiveness and explosiveness.

Chromosomal pathology - Patau syndrome

Children with chromosomal pathology Patau syndrome have multiple malformations. Patau syndrome - 47.XX.13+ and 46.XY. t 13/15 is rare, one child in 6000 children on average. All children with this pathology have multiple malformations. In children who survived, in 100% of cases, mental retardation, craniofacial dysmorphia - narrow eyes, low-lying, irregularly shaped ears, low heavy forehead, cleft lip, palate.

Chromosomal pathology - Edwards syndrome

The risk of fetal chromosomal pathology of Edwards syndrome is low, one child per 6,000 children on average. Pathology is accompanied by multiple malformations in all sick children. Patients have malformations of the heart, brain, lungs, intestines, skull and skeleton. Boys die after birth, girls mostly live to one month, a very small percentage of girls can live to one year.

Chromosomal pathologies - Edwards and Patau are not inherited due to the fact that sick children do not survive to adulthood due to numerous malformations.

Chromosomal pathology - Shereshevsky-Turner syndrome

The risk of fetal chromosomal pathology - Shereshevsky-Turner syndrome is 1 to 3500. The karyotype of the disease is 45.X. The pathology is characterized by an antimongoloid incision of the eyes, in 65% of cases there is lymphatic edema of the feet, legs, hands in a newborn baby, which can manifest itself during the first months of a baby's life. Pathology has pronounced signs - a short neck, which occurs in half of the cases of pathology, pterygoid folds (sphinx neck) from the back of the head to the shoulder girdle, are found in 65% of cases. All children with Shereshevsky-Turner syndrome short stature, barrel-shaped breasts with widely spaced nipples occur in 55% of cases. With a 45.X karyotype, sexual infantilism is diagnosed in all sick children. Pathology is characterized by underdevelopment of the mammary glands, amenorrhea, emotional poverty. Pathology is treated by stimulating the growth of the child, the formation menstrual cycle by using hormone therapy, according to indications, surgical treatment, psychotherapeutic treatment are used.

Chromosomal pathology - Klinefelter's syndrome

The risk of chromosomal pathology of the fetus - Klinefelter's syndrome, is 1 in 600 on average. These are the boys who have further high growth, female body type, gynecomastia in 100% of cases. Pathology karyotype - 47.XXY, 48.XXXY; 47.XYY; 48.XYYY; 49.XXXYY; 49. XXXXY.

People with this pathology are prone to suggestibility, emotional lability. They have Long hands, fingers, in 100% of cases microorchidism, during puberty there are clear signs of pathology - there is practically no hair growth in the genital area, hyalinosis of the spermatic cords and degeneration of the epithelium, infertility. Patients are apathetic, lack of initiative, prone to depressive psychosis, alcoholism, antisocial behavior in society. In childhood, patients are asthenic, adults suffer from increased body weight.

Patients with Klinefelter's syndrome and polysomy 47. XYY may look like absolutely healthy people, most of the patients have mental development close to normal or slightly reduced. Some patients differ aggressive behavior, have a good physique, well-developed muscles, they are tall. It is noted that among recidivist criminals there are often patients with this type of polysomy.

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