Why is it called Down's disease? What genetic causes are risk factors? What about other countries

Down syndrome is a genetic disorder in which a person instead of 46 chromosomes has 47 due to the fact that one extra chromosome appears in their 21st pair.

Down syndrome has been known to mankind since ancient times, back in the 19th century, doctors observed children with a set of characteristic features of appearance, trying to understand what unites them and why such children are born. And in 1862, the English scientist John Langton Down first described the syndrome, but due to the level of development of medicine at that time, he attributed it to mental disorders, because he was not available electron microscopes to find real reason anomalies.

Most children with this syndrome died before reaching adulthood. With the development of civilization and science, when doctors learned to stop at least a number of symptoms, their life span increased, and the number of adults suffering from Down syndrome increased. But society was in no hurry to accept them - at the beginning of the 20th century, in some countries, adults with this diagnosis were subjected to forced sterilization, and in Nazi Germany and its occupied territories, it was ordered to clear the population of such patients. And only since the second half of the 20th century, humanity has finally come to grips with this problem.

It was very important to find the cause of the syndrome. Despite the fact that the relationship between the age of the parents and the possibility of having a Down child has long been noticed, the causes of the disease were looked for either in the psyche, or in heredity, or in difficult childbirth. Finally, in 1959, the French scientist Jerome Lejeune suggested that the source of the disease lies somewhere in the chromosomes. Having studied the karyotype of patients, he established a connection between the existing third chromosome in the 21st pair and the presence of the disease. It was also confirmed that the possibility of having such a child is influenced by the age of the parents, and the mother to a greater extent than the father. If the mother is between 20 and 24 years old, the probability of this is 1 in 1562, under 30 years old - 1 in 1000, from 35 to 39 years old - 1 in 214, and over the age of 45, the probability is 1 in 19. Although the probability increases with the age of the mother , 80% of children with this syndrome are born to women under the age of 35 years. This is due to the higher birth rate in this age group. According to recent data, paternal age, especially if older than 42 years, also increases the risk of the syndrome. At the same time, the behavior of parents, their lifestyle and nationality do not affect this possibility in any way: Down children are born with the same frequency, regardless of nationality, place of residence and other factors.
Down syndrome is not a rare pathology. According to statistics, one in 700 conceived children is a carrier, but among children born, the number of carriers decreases to one in 1,100 children. This discrepancy is explained by the fact that some pregnancies are interrupted naturally, a miscarriage occurs, and, which is very painful to talk about, very often women, having learned that they will have a child with this syndrome, have an abortion. In the last decade, religious and public organizations around the world, including the Russian Orthodox Church in Russia, draws public attention to this problem, to the ethical side, explaining that Down syndrome is not as terrible as it might seem, therefore, it is gradually possible to reduce the number of abortions, in connection with which it increases annually the number of registered cases of the birth of children with Down syndrome.

In humans, Down syndrome is usually associated only with mental retardation. However, polysomy on the 21st pair of chromosomes causes much more complications in the human body than it might seem at first glance. People with Down syndrome are most often diagnosed with:

"flat face" - 90%
brachycephaly (abnormal shortening of the skull) - 81%
skin fold on the neck in newborns - 81%
epicanthus (vertical skin fold covering the medial canthus) - 80%
joint hypermobility - 80%
muscular hypotension - 80 %
flat nape - 78%
short limbs - 70 %
brachymesophalangia (shortening of all fingers due to underdevelopment of the middle phalanges) - 70%
cataract over the age of 8 years - 66%
open mouth (due to low muscle tone and the special structure of the palate) - 65%
dental anomalies - 65%
clinodactyly of the 5th finger (curved little finger) - 60%
arched palate - 58%
flat nose bridge - 52%
furrowed tongue - 50%
transverse palmar fold (also called "monkey") - 45%
short wide neck - 45%
CHD (congenital heart disease) - 40%
short nose - 40 %
strabismus (strabismus) - 29%
deformation chest, keeled or funnel-shaped - 27%
age spots on the edge of the iris = Brushfield spots - 19%
episyndrome - 8%
stenosis or atresia duodenum - 8 %
congenital leukemia - 8%

However, at the same time, it is necessary to know that the diagnosis is made solely on the basis of the results of a blood test for the karyotype. It is impossible to make a diagnosis of "Down's syndrome" based only on external signs.

How is the life of a person with such a diagnosis?

Despite the fact that most people with Down syndrome suffer from mental retardation and delayed psycho-speech development, this condition is successfully corrected by rehabilitation measures carried out in childhood. Experience shows that with the right attitude towards the child on the part of the parents, he is not much different from ordinary children. Down children are trainable, they relatively easily master the usual household skills. Moreover, people with Down syndrome are able to achieve good success in the profession: they can work as waiters, administrators, sellers, receptionists, storekeepers. Actor Chris Burke lives in the United States, known to the Russian audience for the films ER and Mona Lisa Smile, who has Down syndrome. The Portuguese Pablo Pineda became the first person in Europe with Down syndrome who received a university education and chose the profession of a teacher. Society, inspired by the examples of these people, should stop shying away from those who live with Down syndrome. It's not the best serious disease of the existing ones, although, of course, the upbringing and adaptation of a child with such a syndrome requires a lot of physical and emotional feedback from parents.

People with Down syndrome successfully marry, with most men being sterile and 50% of women being fertile and having children. Paired with healthy man+ Down woman The probability of having a child with Down syndrome reaches 50%, the other 50% of children are born healthy.

The average life expectancy of people with Down syndrome in modern conditions is over 50 years old. However, due to existing congenital diseases, they develop Alzheimer's disease (senile dementia) much earlier than healthy people, in addition, with age, the state of health is complicated by the development cardiac diseases and leukemias. In addition, such people have a weakened immune system, and in principle they get sick more often, more severely and for longer than ordinary people.

The main problem of people with Down syndrome at this stage is the reaction of society to them. Unfortunately, many people in Russia have not learned to perceive them as full-fledged members of society, Down people cause fear and rejection, they are extremely reluctant to hire out of fear that they will not cope with their duties, and because of their “unrespectable” appearance . Another important problem is the high number of abortions performed by women whose fetus has the syndrome. According to statistics, even in prosperous economically developed countries, in 90% of cases, women decide to terminate a pregnancy. Church communities should intensify their work aimed at explaining that it is quite possible to live with Down syndrome, it is necessary to convince mothers that abortion with such a diagnosis is a mistake.

Down syndrome is one of those diseases that scares pregnant women who are waiting for the first studies. The frequency of occurrence is quite high - one baby is about 700 healthy. Recently, however, statistics have declined - now a child with such a disorder is born in about 1,100 healthy children. The reason for this was the spread of prenatal diagnosis in the early stages, which makes it possible to identify pathology and terminate a pregnancy.

The spread of prenatal diagnosis at an early stage has significantly reduced the number of children born with Down syndrome

Risk factors

Every year, about five thousand children with Down syndrome appear in the world, according to statistics. There was no dependence on the sex or nationality of the child - the disease is equally common in all regions. There is only a strong dependence of the probability of developing the disease on the age of the expectant mother:

• 20-24 years old - 1 chance in 1562;
• 25-35 years old - 1/1000;
• 35-39 years old - 1/214;
• after 45 - 1/19.

As you can see, the risk is directly proportional to the age of conception. For men, an increase in the risk of conceiving a child with a pathology after 42 years was revealed.

Pathogenesis

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Pathology is caused by a chromosomal mutation, as a result of which an “extra” chromosome is formed, completely or partially copying the genetic material of chromosome number 21. If the genetic set healthy person make up 46 chromosomes, then a person with Down syndrome has 47 chromosomes in the karyotype.

Why this happens is not exactly known. The causes of Down's syndrome have nothing to do with the circumstances of the parents' lives, their intake of any medications, or other risk factors. The only clearly established dependence is the age of the mother, however, the mechanism of dependence remains unidentified. Such a division of the chromosome is an accident of a fatal kind, it is impossible to prevent or change it.

Signs of the disease

External signs of Down syndrome are quite characteristic and can be seen already in newborns. The following symptoms are highly likely to indicate the presence of Down syndrome:

• small head;
• small, often open mouth;
• miniature chin;
• flattened short skull;
• flattened bridge;
• deformed ears;
• almond-shaped incision of the eyes;
• epicanthus on the inner edge of the eyelid (regardless of nationality);
• short neck with skin folds;
• short fingers and limbs;
• wide flat palms with a horizontal fold;
• concave little fingers;
• a large distance between the big and index toes;
• weakened general tone.

The signs and symptoms of Down syndrome appear in a complex, therefore external diagnostics Down syndrome in newborns is quite accurate. The diagnosis is confirmed by a genetic study of the karyotype. Down syndrome of the mosaic type is the most difficult to determine, since not all cells of such a patient contain an extra chromosome.

Effects

The consequences may vary depending on the amount of excess genetic material and the genetic environment. Children with Down syndrome usually have a weakened immune system, so they are more likely to get ARVI and diseases associated with the respiratory and digestive organs, they tolerate childhood infections worse. In the first five years of life, such infections and the consequences of congenital comorbidities pose the greatest danger.

Also among the signs of Down syndrome are mental retardation, mild or moderate mental retardation, a lag in the development of motor skills and a general underdevelopment of speech abilities. In grown-up patients, there is a noticeable lag in growth - about twenty centimeters in comparison with the expected norm. At favorable conditions patients live approximately 50-60 years. How long will a particular patient live? to a large extent depends on severity related complications.

In patients with Down syndrome, the nervous, digestive and reproductive system are at particular risk. Can develop early illness Alzheimer's, obesity or testicular cancer. Men are usually infertile, women are often capable of pregnancy and childbearing, but their fertility is reduced.

Heredity

Trisomy 21, which is the cause of about 9 out of 10 cases of the disease, and the rare mosaic Down syndrome are not usually inherited. A translocation form of the disease can have a genetic condition, when one of the parents had a chromosomal exchange that did not lead to pathology, which caused an excess of the genetic material of chromosome 21. When transmitted, such translocation sites can provoke the occurrence of a violation in the offspring.

Theoretically, the birth of a healthy child in a woman with the syndrome is possible, but unlikely due to the usual related disorders reproductive development.

Preliminary diagnostics

Complex medical research to diagnose Down syndrome during pregnancy is called prenatal screening.

1. In the first trimester, it is carried out at 11-13 weeks, it includes the identification of signs of pathology by ultrasound and through a blood test for specific biochemical markers.
2. This is followed by a second trimester screening, performed at 16-22 weeks - an obstetric ultrasound and a blood test for the following markers. The risk of having a child with Down syndrome can be calculated depending on the age of the pregnant woman with an accuracy of 56 to 70% and 5% of false positive results. In addition, it is almost impossible to determine the mosaic type in this way.

Women at risk are offered additional diagnostic measures: amnio- or cordocentesis with fetal karyotyping, chorion biopsy, medical genetics consultation. If the study yields positive results about the presence of a pathology, it is up to the parents to decide whether to terminate or continue the pregnancy.

Reducing the consequences of the disease

In the first days of life, infants with a disorder should undergo ultrasound and echocardiogram to identify concomitant developmental pathologies. internal organs. Also, children need to be examined by children's specialists: pediatric cardiologist, ophthalmologist, surgeon and traumatologist-orthopedist.

On the this moment it is impossible to cure a chromosomal mutation. Existing Methods theoretically complete cures are experimental and do not have clinically proven effectiveness, however, it is possible to achieve some success in the psychosocial development of children with this deviation with the help of systematic medical supervision and specialized pedagogical intervention. This is not about treating Down syndrome itself, but about minimizing the associated difficulties.

Because of the abundance additional pathologies or a high risk of their development, a person with Down syndrome is shown to be under the constant supervision of doctors: a therapist, cardiologist, endocrinologist, neurologist and other specialists.

• Severe congenital malformations of the digestive system and heart are subject to surgical treatment at a very early age.
• If vision or hearing is impaired, glasses are selected or hearing aid In some cases, surgery may also be needed.
• With endocrinological disorders, hormone therapy is selected.
• To reduce the level of backlog in physical characteristics, exercise therapy and physiotherapy are recommended.
• Correction of speech disorders and mastery of communication skills is carried out with the help of a speech therapist and an oligophrenopedagogue.

Social aspects

Children with Down syndrome are most often educated in special schools for children with developmental disabilities or in remedial classes. It is possible to attend a regular school if integrated education is organized. "Sunny children" need adapted educational programs, additional attention of social pedagogues and teachers, and the availability of a comfortable and safe environment for their development.

It is important to maintain right attitude peers to special children, as well as to provide psychological and pedagogical consultations for families raising children with this disorder. Attitudes towards those suffering from this disease should be formed taking into account the fact that Down syndrome is not a profound disability, and that these people are capable of learning, developing and socializing.

However, it is important to understand that mental and physical development will be noticeable to some extent. It would not be correct to compare a child with Down syndrome with ordinary children, but this does not mean that such a child cannot become a useful and adapted member of society. An individual development program is very important, taking into account all the characteristics of a particular child - then the results of the correction will be the most favorable.

Down syndrome is a genetic anomaly resulting from the bifurcation of one of the 21 chromosomes, as a result of which the human chromosome set includes not 46, but 47 chromosomes, which causes further clinical signs.

The phenomenon was first described by the English physician John Down (thanks to whom the syndrome got its name) in 1866 as mental retardation with characteristic external signs, but only in 1959 did the French geneticist Jerome Lejeune determine the connection excess chromosome number and symptoms of the syndrome.

Today, despite the development medical technologies, Down syndrome is a very common and not fully understood phenomenon, which gives rise to many different myths, sometimes contradicting each other. However, it is known that:

1. This anomaly is equally common in both sexes, different ethnic groups and nationalities.
2. The development of the syndrome does not depend on the lifestyle of the parents and has a genetic "origin", when anomalies occur either at the stage of egg or sperm formation (it is not excluded, but it is practically unlikely that they can be affected harmful factors external environment), or during the fusion of germ cells after fertilization.
3. The syndrome occurs when pathological processes in genes, when 1 more chromosome joins the 21st pair (that's why they get 47 instead of 46). Most often this is due to the fact that during cell division, the chromosomes do not diverge. In addition, one of the main reasons may be the heredity of the mutation of the 21st chromosome - when this chromosome merges with another. This mutation is called trisomy and occurs in about one in 800 newborns, and 88% of cases are due to the "non-disjunction" of female gametes (reproductive cells).
4. Down Syndrome - frequent pathology, which has 3 forms ( hereditary disease, mutation of the 21st chromosome, mosaic disease) and 4 degrees of the disease:

• weak - patients practically do not differ from ordinary children, quite often they successfully adapt in society and can occupy a very prestigious place in society;
• average;
• heavy;
• deep - children cannot lead the generally accepted way of life of society, and this greatly complicates the life of parents. Nowadays, there is a special prenatal diagnosis that allows you to find out in time about the likelihood of developing a pathology. If you suspect Down's syndrome, parents face the question: leave the child or get rid of the pregnancy? At the birth of a baby, others will arise: how to raise a child, how to provide him with a normal life and at the same time live fully on his own?

5. Down syndrome is not recommended to be called a disease, since people living with this syndrome, although they have pathological changes preventing them from realizing their full potential, however, with right approach specialists from early years most are able to adapt well enough in society.

Causes of the development of Down syndrome

As we have already said, Down syndrome occurs due to an anomaly cell division when one more third chromosome is glued to the 21st pair of chromosomes. In other words, it is a congenital pathology that cannot be obtained in the course of life. The reasons chromosomal disorders very difficult to install.

This happens as a result of 3 forms of pathology that have an almost identical clinical picture of this syndrome:

1. Trisomy- a subspecies of the syndrome, characterized by the formation of three chromosomes in 21 pairs. This phenomenon has been little studied, but there is a version that the age of the mother plays a significant role here: the older the woman, the Great chance have a baby with Down syndrome. This is due to the age of the egg, when the birth of a gamete is possible not with 23, but with 24 chromosomes. In this case, when a cell is fertilized by a male gamete with 23 chromosomes, one remains superfluous, and a mutation occurs: the chromosome sticks (attaches) to 21 pairs. As a result, all cells of the fetus will contain 47 chromosomes.
2. mosaicism- a rare phenomenon (make up only 1-2% of all cases), in which not all cells of the fetus will contain an abnormal number of chromosomes, therefore only individual bodies and tissues (if copying falls on the genes responsible for mental and motor development, then the development of the syndrome in the fetus cannot be avoided). This is due to the "non-disjunction" of the chromosome series not at the stage of formation of parent germ cells, but at the early stages of development of the embryo. This form of the syndrome - with a smoothed clinical picture - is mild, but during perinatal studies it is extremely difficult to diagnose.
3. Translocation- occurs during cell fusion and at the same time, a shift of a part of one chromosome in the 21st pair to the side of the other chromosome is noted.

However, there are other reasons for the development of Down syndrome:

1. The age of the parents is too young a girl, or, conversely, a woman over 40 years old, and for men - over 45 years old (the risk of having a child with the syndrome is 1:30). Due to age, the maturation and division of chromosomes “slow down”, and a defective cell is obtained. Being involved in fertilization, it will subsequently become the cause of the development of Down syndrome.
2. Closely related marriage (bond).
3. Folic acid deficiency during pregnancy.
4. The likelihood of having a child with Down syndrome increases if the disease occurs in the family of the parents.

Down Syndrome Symptoms

The disease is usually called a syndrome, since it is characterized by a number of symptoms and signs, as well as characteristic manifestations:

• narrow and slanted (Mongoloid) eyes ( earlier pathology was called "Mongolism");
• the presence of an epicanthus (a special fold at the inner corner of the eye, which covers the lacrimal tubercle and does not pass to the upper eyelid);
• strabismus and noticeable pigmentation of the iris (Brushfield spots), cataracts are possible;
• flat profile - flat and wide bridge of the nose and short nose, occipital region;
• shortened (small) skull;
• shortened neck - the newborn has a fold of skin in this area;
• underdeveloped auricles;
• hypotension (weak tone) of the muscles;
• an arched palate, an abnormally large tongue (macroglossia) and an open mouth due to reduced muscle tone;
• wide hands with short fingers due to underdevelopment of the middle phalanges - there is a curvature in the little finger,
• on the palms there is a single transverse fold;
• short limbs;
• there is a deformation (keeled or funnel-shaped) of the chest;
• often (about 40%) children with the syndrome are born with congenital heart disease (defective processes in the septum between the ventricle), which is one of the main causes of their mortality;
• pathological processes of the gastrointestinal tract (for example, duodenal artesia);
• the child may be born with leukemia;
• the child lags behind in growth, mental development;
• hoarse voice;
• most often, patients are infertile, but when offspring appear, children have the same pathology.

However, it is worth noting that people with Down syndrome rarely have malignant tumors, and this is due to the protection of the extra gene.

At the birth of twins, the syndrome is observed in both children.

The severity of the above symptoms in all patients is different.

Diagnosis of Down syndrome

The modern level of medicine and technology in case of suspected Down's syndrome makes it possible to carry out timely diagnosis and if DNA abnormalities are found, get rid of the current pregnancy.

For diagnosis, several methods are used:

1. Ultrasound - carried out in the 2nd or 3rd trimester of pregnancy, when a fetus is scanned to detect pathology. This method makes it possible to "see" the signs of Down syndrome with the help of some "measurements":

• thickening of the collar space (with developing syndrome it will be more than 3 mm);
• absence of the nasal bone;
• small sizes of the frontal lobe and cerebellum (hypoplasia);
• shortened femurs and ulnas, etc.

However, ultrasound reveals only one of the forms of the syndrome - trisomy. The remaining subspecies of pathology cannot be detected by this diagnostic method.

2. Biochemical analysis of the blood of a pregnant woman in the 1st trimester (to establish the karyotype - the gene content of the mother's blood), during which the level of the hormone synthesized by the fetus (hCG) and PAPP-A is taken into account. In the 2nd trimester, the analysis is carried out again.

3. A biochemical test (by the level of free chorionic hormone) makes it possible to diagnose Down syndrome as early as the 12th week of pregnancy, and at the 16th week, a test for estriol and α-faetoprotein is carried out - indicators of the presence of Down syndrome. When confirming the data, you must immediately contact a geneticist who prescribes:

• choriobiopsy - a study of the tissues of the fetal membrane;
• amniocetesis (analysis of amniotic fluid) - the study of the cellular composition of amniotic fluid, as well as baby tissues, which will provide information about the cellular set of chromosomes of the child;
• cordocentesis - analysis of the umbilical cord blood of the fetus.

These methods are highly accurate, but, unfortunately, are not safe for a woman - they can lead to complications, up to a miscarriage, and therefore are carried out only in extreme cases(if the age of the pregnant woman is over 35, if there is a suspicion of a syndrome in ultrasound studies, or if there is a disease in the family).

However, science does not stand still, and London clinics have already developed a special test that allows you to accurately find out about all genetic diseases.

Down syndrome treatment

Down syndrome is an incurable disease, since no one can “correct” DNA, but it is possible to improve the general condition of the patient and improve his quality of life.

Treatment congenital pathologies conducted by specialists - pediatrician, cardiologist, gastroenterologist, ophthalmologist and others. Their efforts are aimed at improving the health of the patient, and despite the fact that there is no specific treatment for the syndrome, it is still impossible to avoid taking medications. Among them:

• Piracetam, Aminolone, Cerebrolysin - to normalize blood circulation in the brain;
• neurostimulators;
• vitamin complexes - to improve overall health.

However, quite often, with age, children with Down syndrome show a number of complications associated with physical health: diseases of the heart and digestive organs, disorders of the endocrine and immune systems, problems with hearing, sleep, vision, cases of respiratory arrest are not uncommon. In addition, almost a quarter of patients after 40 years of age (and sometimes even earlier) have obesity, epilepsy, Alzheimer's disease and leukemia. At the same time, it is difficult to predict how the disease will develop, because everything depends on the individual characteristics of the organism, the degree of the disease and the activities with the child. Few people with Down syndrome live to be 50 years old.

At the same time, a speech therapist, a neuropathologist and other specialists are dealing with the elimination of significant disorders of verbal and motor functions, delays intellectual development; self-care skills training. Based on this, children with Down syndrome are recommended to be sent to specialized educational institutions.

To correct mental retardation, specially designed training programs are used, and it is worth noting that mental and cognitive symptoms in each individual case are expressed differently.

Depending on the degree of damage and the treatment (training with the child), a significant reduction in developmental delay can be achieved. With regular activities with the baby, he is able to learn to walk, talk, write and serve himself. Children with Down syndrome can attend public schools, go to college, get married, and in some cases even have children of their own.

Among people with Down syndrome there are a lot of artists, writers, artists. There is even an opinion that the “children of the sun” are not just a genetic disease, but a separate “species” of people who not only differ in the presence of an “extra” chromosome, but live according to their own moral laws and have their own principles.

People with Down syndrome are often referred to as "children of the sun" or "sunshine" because they are constantly smiling, gentle, kind, and radiate warmth. In 2006, the International Down Syndrome Day was established, which is celebrated around the world on March 21.

Special for - Kira Danet

- a chromosomal anomaly in which the karyotype contains additional copies of genetic material on the 21st chromosome, i.e. trisomy on chromosome 21 is observed. The phenotypic signs of Down syndrome are represented by brachycephaly, a flat face and back of the head, a Mongoloid incision palpebral fissures, epicantoma, skin fold on the neck, shortening of the limbs, short fingers, transverse palmar fold, etc. Down syndrome in a child can be detected prenatally (according to ultrasound, chorionic villus biopsy, amniocentesis, cordocentesis) or after birth based on external signs and genetic testing . Children with Down syndrome need correction of concomitant developmental disorders.

Causes of Down syndrome

Normally, the cells of the human body contain 23 pairs of chromosomes (normal female karyotype 46,XX; male - 46,XY). In this case, one of the chromosomes of each pair is inherited from the mother, and the other from the father. The genetic mechanisms of the development of Down's syndrome lie in the quantitative violation of autosomes, when additional genetic material is attached to the 21st pair of chromosomes. The presence of trisomy on the 21st chromosome determines the features characteristic of Down syndrome.

The appearance of an additional chromosome may be due to genetic accident (non-disjunction of paired chromosomes in ovogenesis or spermatogenesis), a violation of cell division after fertilization, or the inheritance of a genetic mutation from the mother or father. Given these mechanisms, genetics distinguishes three variants of karyotype anomalies in Down syndrome: regular (simple) trisomy, mosaicism, and unbalanced translocation.

Most cases of Down syndrome (about 94%) are associated with simple trisomy (karyotype 47,XX, 21+ or 47,XY, 21+). At the same time, three copies of the 21st chromosome are present in all cells due to a violation of the separation of paired chromosomes during meiosis in the maternal or paternal germ cells.

About 1-2% of cases of Down syndrome occur in the mosaic form, which is caused by a violation of mitosis in only one cell of the embryo, which is at the blastula or gastrula stage. With mosaicism, trisomy of the 21st chromosome is detected only in the derivatives of this cell, and the rest of the cells have a normal chromosome set.

The translocation form of Down syndrome occurs in 4-5% of patients. In this case, the 21st chromosome or its fragment is attached (translocated) to any of the autosomes and, during meiosis, moves along with it into the newly formed cell. The most frequent "objects" of translocation are chromosomes 14 and 15, less often - on 13, 22, 4 and 5. Such rearrangement of chromosomes can be random or inherited from one of the parents, who is a carrier of a balanced translocation and has a normal phenotype. If the father is the carrier of the translocation, then the probability of having a child with Down syndrome is 3%; if the carrier is associated with maternal genetic material, the risk increases to 10-15%.

Risk Factors for Having Children with Down Syndrome

The birth of a child with Down syndrome is not associated with the lifestyle, ethnicity and region of residence of the parents. The only reliably established factor that increases the risk of having a child with Down syndrome is the age of the mother. So, if in women under 25 the probability of having a sick child is 1:1400, by the age of 35 it is already 1:400, by the age of 40 - 1:100; and by 45 - 1:35. First of all, this is due to a decrease in control over the process of cell division and an increase in the risk of chromosome nondisjunction. However, since the frequency of childbirth in young women is generally higher, according to statistics, 80% of children with Down syndrome are born to mothers under the age of 35. According to some reports, the age of the father over 42-45 years also increases the risk of developing Down syndrome in a child.

It is known that in the presence of Down syndrome in one of the identical twins, this pathology in 100% of cases will be present in the other. Meanwhile, in fraternal twins, as well as brothers and sisters, the probability of such a coincidence is negligible. Other risk factors include the presence of persons with Down syndrome in the family, the age of the mother under 18 years of age, the carriage of a translocation by one of the spouses, closely related marriages, random events that disrupt the normal development of germ cells or the embryo.

Thanks to pre-implantation diagnostics, conception with the help of ART (including in vitro fertilization) significantly reduces the risk of having a child with Down syndrome in parents from risk groups, but does not completely exclude this possibility.

Down Syndrome Symptoms

Carrying a fetus with Down syndrome is associated with an increased risk of miscarriage: spontaneous abortion occurs in about 30% of women for a period of 6-8 weeks. In other cases, children with Down syndrome, as a rule, are born full-term, but have moderately pronounced hypoplasia (body weight is 8-10% below average). Despite various cytogenetic variants of a chromosomal anomaly, most children with Down syndrome are characterized by typical external signs that suggest the presence of a pathology already at the first examination of a newborn by a neonatologist. Children with Down syndrome may have all or some of the physical characteristics described below.

80-90% of children with Down syndrome have craniofacial dysmorphias: a flattened face and bridge of the nose, brachycephaly, a short wide neck, a flat nape, deformity of the auricles; newborns - a characteristic skin fold on the neck. The face is distinguished by a Mongoloid incision of the eyes, the presence of an epicanthus (a vertical fold of skin covering the inner corner of the eye), microgenia, a half-open mouth, often with thick lips, and a large protruding tongue (macroglossia). Muscle tone in children with Down syndrome is usually lowered; there is hypermobility of the joints (including atlanto-axial instability), deformity of the chest (keeled or funnel-shaped).

The characteristic physical signs of Down syndrome are meek limbs, brachydactyly (brachymesophalangia), curvature of the little finger (clinodactyly), a transverse ("monkey") crease in the palm, a wide distance between 1 and 2 toes (sandal gap), etc. When examining children with the syndrome Down revealed white spots along the edge of the iris (Brushfield spots), gothic (arched palate), malocclusion, furrowed tongue.

With the translocation variant of Down's syndrome, external signs are more pronounced than with simple trisomy. The severity of the phenotype in mosaicism is determined by the proportion of trisomic cells in the karyotype.

Children with Down syndrome are more likely than others in the population to have CHD (open ductus arteriosus, VSD, ASD, tetralogy of Fallot, etc.), strabismus, cataracts, glaucoma, hearing loss, epilepsy, leukemia, gastrointestinal tract defects (esophageal atresia, stenosis and duodenal atresia, Hirschsprung disease), congenital dislocation of the hip. characteristic dermatological problems puberty are dry skin, eczema, acne, folliculitis.

Children with Down syndrome are often ill; they are more difficult to tolerate childhood infections, more often suffer from pneumonia, otitis media, SARS, adenoids, tonsillitis. Weak immunity and birth defects are the most probable cause death of children in the first 5 years of life.

Most people with Down syndrome have intellectual disabilities - usually mental mild retardation or medium degree. The motor development of children with Down syndrome lags behind their peers; there is a systemic underdevelopment of speech.

Down syndrome patients are prone to developing obesity, constipation, hypothyroidism, alopecia areata, testicular cancer, early onset Alzheimer's disease, and others. Men with Down syndrome are generally infertile; female fertility is markedly reduced due to anovulatory cycles. The height of adult patients is usually 20 cm below average. Life expectancy is about 50-60 years.

Diagnosis of Down syndrome

For prenatal detection of Down's syndrome in the fetus, a system of prenatal diagnosis has been proposed. Screening of the first trimester is carried out at a gestational age of 11-13 weeks and includes the identification of specific ultrasound signs of anomalies and the determination of the level of biochemical markers (hCG, PAPP-A) in the blood of a pregnant woman. Between 15 and 22 weeks of pregnancy, second trimester screening is performed: obstetric ultrasound, maternal blood test for alpha-fetoprotein, hCG and estriol. Taking into account the woman's age, the risk of having a child with Down syndrome is calculated (accuracy - 56-70%; false positive results - 5%).

Pregnant women at risk for giving birth to a child with Down syndrome are offered prenatal invasive diagnostics: chorion biopsy, amniocentesis or cordocentesis with fetal karyotyping and medical genetics consultation. Upon receipt of data for the presence of Down syndrome in a child, the decision on the prolongation or termination of pregnancy remains with the parents.

Newborns with Down's syndrome in the first days of life need a cardiologist, a speech therapist and an oligophrenic pedagogue.

Education of children with Down syndrome is usually carried out in a special correctional school However, within the framework of integrated education, such children can also attend a regular mass school. In all cases, children with Down syndrome are classified as children with special needs. educational needs, so they need additional help teachers and social educators, the use of special educational programs creating a favorable and safe environment. Important role psychological and pedagogical support of families where "sunny children" are brought up.

Forecast and prevention of Down syndrome

Opportunities for learning and socialization of individuals with Down syndrome are different; they largely depend on the intellectual abilities of children and on the efforts made by parents and teachers. In most cases, children with Down syndrome manage to instill the minimum household and communication skills needed in everyday life. At the same time, cases of success of such patients in the field of fine arts, acting, sports, as well as obtaining higher education. Adults with Down syndrome can lead an independent life, master simple professions, and create families.

We can speak about the prevention of Down syndrome only from the standpoint of reducing possible risks, since the probability of having a sick child exists in any couple. Obstetrician-gynecologists advise women not to delay pregnancy for late age. Predicting the birth of a child with Down syndrome is intended to help genetic counseling of families and the system of prenatal screening.

A genetic pathology caused by changes in the 21st chromosome is a mosaic Down syndrome. Consider its features, methods of diagnosis, treatment and prevention.

Down's disease is one of the most common congenital genetic disorders. It is characterized by a pronounced mental retardation and a number of intrauterine anomalies. Due to the high birth rate of children with trisomy, many studies have been conducted. Pathology occurs in representatives of all peoples of the world, so no geographical or racial dependence has been established.

ICD-10 code

Q90 Down syndrome

Epidemiology

According to medical statistics, Down syndrome occurs in 1 child in 700-1000 births. The epidemiology of the disorder is associated with certain factors: hereditary predisposition, bad habits of parents and their age.

The pattern of the spread of the disease is not related to the geographical, gender, nationality or economic status of the family. Trisomy is caused by disturbances in the development of the child.

Causes of Mosaic Down Syndrome

The main causes of mosaic Down syndrome are associated with genetic disorders. A healthy person contains 23 pairs of chromosomes: female karyotype 46,XX, male 46,XY. One of the chromosomes of each pair is transmitted from the mother, and the second from the father. The disease develops as a result of a quantitative violation of autosomes, that is, excess genetic material is added to the 21st pair. Trisomy 21 is responsible for the symptoms of the defect.

Mosaic syndrome can occur for the following reasons:

• Somatic mutations in the zygote or in the early stages of cleavage.
• Redistribution in somatic cells.
• Segregation of chromosomes during mitosis.
• Inheritance of a genetic mutation from mother or father.

The formation of abnormal gametes may be associated with certain diseases of the genital area of ​​the parents, radiation, smoking and alcoholism, taking medications or drugs, as well as with the environmental situation of the place of residence.

About 94% of the syndrome is associated with simple trisomy, that is: karyotype 47, XX, 21+ or 47, XY, 21+. Copies of the 21st chromosome are in all cells, since during meiosis in parent cells division of paired chromosomes is disturbed. About 1-2% of cases are due to impaired mitosis of embryonic cells at the gastrula or blastula stage. Mosaicism is characterized by trisomy in derivatives of the affected cell, while the rest have a normal chromosome set.

In the translocation form, which occurs in 4-5% of patients, the 21st chromosome or its fragment is translocated to the autosome during meiosis, penetrating with it into the newly formed cell. The main objects of translocation are 14, 15, less often 4, 5, 13 or 22 chromosomes. Such changes can be accidental or inherited from a parent who is a carrier of a translocation and a normal phenotype. If the father has such disorders, then the risk of having a sick child is 3%. When carried by the mother - 10-15%.

Risk factors

Trisomy is a genetic disorder that cannot be acquired in a lifetime. Risk factors for its development are not related to lifestyle or ethnicity. But the chances of giving birth to a sick child increase under such circumstances:

• Late birth - women in labor 20-25 years old have minimal chances of giving birth to a baby with the disease, but after 35 years the risk increases significantly.
• Father's age - many scientists argue that a genetic disease depends not so much on the age of the mother, but on how old the father is. That is, the older the man, the higher the chances of pathology.
• Heredity - medicine knows the case when the defect was inherited from close relatives, given that both parents are absolutely healthy. However, there is a predisposition to only certain types of the syndrome.
• Incest - marriages between blood relatives entail genetic mutations of varying severity, including trisomy.
• Bad habits - negatively affect the health of the unborn baby, so tobacco abuse during gestation can lead to genomic abnormalities. The same is true for alcoholism.

There are suggestions that the development of malaise may be associated with the age at which the grandmother gave birth to the mother and other factors. Thanks to preimplantation diagnosis and other research methods, the risk of having a Down child is significantly reduced.

Pathogenesis

Development genetic disease associated with a chromosomal abnormality, in which the patient has 47 chromosomes instead of 46. The pathogenesis of mosaic syndrome has a different mechanism of development. Sex cells-gametes of parents have a normal number of chromosomes. Their fusion resulted in the formation of a zygote with a 46,XX or 46,XY karyotype. In the process of dividing the original cell, the DNA failed, and the distribution was incorrect. That is, some of the cells received a normal karyotype, and some - a pathological one.

This kind of anomaly occurs in 3-5% of cases. She has a positive prognosis because healthy cells partially compensate for the genetic disorder. Such children are born with external signs of the syndrome and developmental delay, but their survival rate is much higher. They are less likely to have internal pathologies that are incompatible with life.

Symptoms of Mosaic Down Syndrome

An abnormal genetic feature of an organism that occurs with an increase in the number of chromosomes has a number of external and internal signs. Symptoms of mosaic Down syndrome are manifested by a lag in mental and physical development.

Main physical symptoms diseases:

• Small and slow growing.
• Muscle weakness, decreased strength function, weakness abdominal cavity(sagging belly).
• Short, thick neck with folds.
• Short limbs and a large distance between the large and index finger on foot.
• Specific skin fold on the palms of children.
• Low set and small ears.
• Distorted shape of the tongue and mouth.
• Crooked teeth.

The disease causes a number of deviations in development and health. First of all, it is cognitive retardation, heart defects, problems with teeth, eyes, back, hearing. Tendency to frequent infectious and respiratory diseases. The degree of manifestation of the disease depends on congenital factors and the right treatment. Most kids are trainable, despite the mental, physical and mental lag.

First signs

Mosaic Down syndrome has less pronounced symptoms, unlike the classic form of the disorder. The first signs can be seen on ultrasound at 8-12 weeks of gestation. They are manifested by an increase in the collar zone. But ultrasound does not give a 100% guarantee of the presence of the disease, but allows you to assess the likelihood of malformations in the fetus.

The most characteristic external symptoms, with their help, doctors presumably diagnose the pathology immediately after the birth of the baby. The defect is characterized by:

• Slanted eyes.
• "Flat" face.
• short head.
• Thickened cervical skin fold.
• Semilunar fold at the inner corner of the eyes.

Upon further examination, the following problems are revealed:

• Decreased muscle tone.
• Increased joint mobility.
• Deformation of the pile of cells (keeled, funnel-shaped).
• Broad and short bones, flat occiput.
• Deformed ears and folded nose.
• Small arched sky.
• Pigmentation along the edge of the iris.
• Transverse palmar crease.

In addition to external symptoms, the syndrome also has internal disorders:

• Congenital heart defects and other disorders of cardio-vascular system, anomalies of large vessels.
• Pathologies from the side respiratory system caused by structural features of the oropharynx and a large tongue.
• Strabismus, congenital cataract, glaucoma, hearing impairment, hypothyroidism.
• Gastrointestinal disorders: intestinal stenosis, atresia of the anus and rectum.
• Hydronephrosis, renal hypoplasia, hydroureter.

The above symptoms require constant treatment to maintain the normal state of the body. It is congenital malformations that are the reason for the short life of downs.

External signs of a mosaic form of Down syndrome

In most cases, the external signs of the mosaic form of Down syndrome appear immediately after birth. Due to the high prevalence of gene pathology, its symptoms are studied and described in detail.

Changes in the 21st chromosome are characterized by such external signs:

1. Abnormal structure of the skull.

This is the most noticeable and pronounced symptom. Normally, babies have a larger head than adults. Therefore, any deformities are visible immediately after birth. The changes concern the structure cranium and facial skull. The patient has a disproportion in the region of the bones of the crown. There is also a flattening of the occiput, a flat face, and pronounced ocular hypertelorism.

1. Eye development disorders.

A person with this disease resembles a representative Mongoloid race. Such changes appear immediately after birth and persist throughout life. In addition, it is worth canceling strabismus in 30% of patients, the presence of a skin fold at the inner corner of the eyelid and pigmentation of the iris.

1. Congenital defects of the oral cavity.

This kind of disorder is diagnosed in 60% of patients. They create difficulties in feeding the child, slowing down his growth. A person with the syndrome has an altered surface of the tongue due to a thickened papillary layer (furrowed tongue). In 50% of cases, there is a gothic palate and violations of the sucking reflex, a half-open mouth (muscular hypotension). In rare cases, there are anomalies such as "cleft palate" or "cleft lip".

1. Wrong shape of the ears.

This violation occurs in 40% of cases. Underdeveloped cartilages form an irregular auricle. Ears can be protruding in different directions or located below eye level. Although the defects are cosmetic, they can cause serious hearing problems.

1. Additional skin folds.

They occur in 60-70% of patients. Each skin fold is caused by the underdevelopment of the bones and their irregular shape (the skin does not stretch). This external sign of trisomy manifests itself as excess skin on the neck, thickening in the elbow joint and a transverse fold in the palm.

1. Pathologies of the development of the musculoskeletal system

Occur due to a violation of intrauterine development of the fetus. Connective tissue joints and some bones do not have time to fully form before birth. The most common anomalies are: short neck, increased mobility joints, short limbs and deformed fingers.

1. Chest deformity.

This problem is associated with underdevelopment of bone tissue. Patients have deformities thoracic spine and ribs. Most often, a protruding sternum above the surface of the chest is diagnosed, that is, a keeled shape and deformation, in which in the area solar plexus there is a funnel-shaped depression. Both disorders persist as they mature and grow. They provoke violations in the structure of the respiratory apparatus and the cardiovascular system. Such external symptoms indicate a poor prognosis of the disease.

The main feature of the mosaic form of Down syndrome is that with it, many of the above symptoms may be absent. This complicates the differentiation of pathology with other chromosomal abnormalities.

Forms

The syndrome has several types, consider them:

• Mosaic - an extra chromosome is not found in all cells of the body. This type of disease accounts for 5% of all cases.
• Family - occurs in 3% of patients. Its peculiarity is that each of the parents has a number of deviations that are not expressed outwardly. During fetal development, part of the 21st chromosome is attached to another, making it a pathological information carrier. Parents with this defect give birth to children with the syndrome, that is, the anomaly is inherited.
• Duplication of part of the 21st chromosome - rare view disease, the peculiarity of which is that the chromosomes are not able to divide. That is, additional copies of the 21st chromosome appear, but not for all genes. pathological symptoms and external manifestations develop in the event that fragments of gons are duplicated, which determine the clinical picture of the defect.

Complications and consequences

Chromosomal mosaicism causes consequences and complications that adversely affect the state of health and significantly worsen the prognosis of the disease.

Consider the main dangers of trisomy:

• Pathologies of the cardiovascular system and heart defects. About 50% of patients have congenital defects that require surgical treatment at an early age.
• Infectious diseases– defects in the immune system provoke hypersensitivity to various infectious pathologies, especially colds.
• Obesity - people with the syndrome are more prone to overweight than in the general population.
• Diseases hematopoietic system. Downs are more likely to suffer from leukemia than healthy children.
• Short life expectancy - the quality and duration of life depends on the severity of congenital diseases, the consequences and complications of the disease. Back in the 1920s, people with the syndrome did not live to be 10 years old, today the age of patients reaches 50 years or more.
• Dementia - dementia and persistent cognitive decline associated with the accumulation of abnormal proteins in the brain. Symptoms of the disorder occur in patients under 40 years of age. This disorder is characterized by a high risk of seizures.
• Stopping breathing during sleep - sleep apnea is associated with an abnormal structure of soft tissues and the skeleton, which are subject to airway obstruction.

In addition to the complications described above, trisomy is characterized by problems with thyroid gland, bone weakness, poor eyesight, hearing loss, early menopause and bowel obstruction.

Diagnosis of mosaic Down syndrome

It is possible to identify a genetic pathology even before birth. Diagnosis of mosaic Down syndrome is based on the study of the karyotype of blood and tissue cells. In early pregnancy, a chorionic biopsy is performed to reveal signs of mosaicism. According to statistics, only 15% of women who have learned about genetic abnormalities in a child decide to leave him. In other cases, premature termination of pregnancy is indicated - abortion.

Consider the most reliable methods trisomy diagnosis:

• Biochemical blood test - blood for research is taken from the mother. biological fluid assessed for β-hCG and plasma protein A. In the second trimester, another test is performed to monitor the levels of β-hCG, AFP and free estriol. Decreased levels of AFP (a hormone produced by the fetal liver) with high probability indicate a disease.

• Ultrasound - performed in each trimester of pregnancy. The first allows you to identify: anencephaly, cervical hygroma, determine the thickness of the collar zone. The second ultrasound makes it possible to track heart disease, anomalies in the development of the spinal cord or brain, disorders of the gastrointestinal tract, hearing organs, and kidneys. In the presence of such pathologies, termination of pregnancy is indicated. The last test, carried out in the third trimester, may reveal minor disorders that can be corrected after childbirth.

The above studies allow you to assess the risk of having a child with the syndrome, but they do not give an absolute guarantee. At the same time, the percentage of erroneous results of diagnostics carried out during pregnancy is small.

Analyzes

Diagnosis of genomic pathology begins during the gestation period. Analyzes are carried out in the early stages of pregnancy. All tests for trisomy are called screenings or screenings. Their questionable results suggest the presence of mosaicism.

• First trimester - up to 13 weeks, an analysis is carried out for hCG (human chorionic gonadotropin) and PAPP-A protein, that is, substances secreted only by the fetus. In the presence of the disease, hCG is increased, and the level of PAPP-A is lowered. With such results, an amnioscopy is performed. Tiny particles of chorion are removed from the uterine cavity of a pregnant woman through the cervix.

• Second trimester - tests for hCG and estriol, AFP and inhibin-A. In some cases, a study of genetic material is carried out. For its fence, a puncture of the uterus is made through the abdomen.

If, according to the results of the analyzes, high risk trisomy, then the pregnant woman is prescribed a consultation with a geneticist.

Instrumental diagnostics

To identify intrauterine pathologies in the fetus, including mosaicism, instrumental diagnostics are indicated. If Down's syndrome is suspected, screenings are done throughout the pregnancy, as well as an ultrasound to measure the thickness of the posterior cervix of the fetus.

The most dangerous method instrumental diagnostics is amniocentesis. This is a study of amniotic fluid, which is carried out for a period of 18 weeks (a sufficient volume of fluid is required). The underlying danger of this analysis is that it can lead to infection of the fetus and mother, rupture of the fetal bladder and even miscarriage.

Differential Diagnosis

The mosaic form of changes in the 21st chromosome requires careful study. Differential diagnosis of Down syndrome is carried out with the following pathologies:

• Klinefelter syndrome
• Shereshevsky-Turner syndrome
• Edwards syndrome
• de la Chapelle syndrome
• congenital hypothyroidism
• Other forms of chromosomal abnormalities

In some cases, mosaicism on the XX/XY sex chromosomes leads to true hermaphroditism. Differentiation is also necessary for mosaicism of the gonads, which are a special case of organ pathology that occurs on late stages embryonic development.

Treatment of mosaic Down syndrome

Therapy of chromosomal diseases is not possible. Treatment of mosaic Down syndrome is lifelong. It is aimed at eliminating malformations and concomitant diseases. A person with this diagnosis is under the control of such specialists: pediatrician, psychologist, cardiologist, psychiatrist, endocrinologist, ophthalmologist, gastroenterologist and others. All treatment is aimed at social and family adaptation. The task of parents is to teach the baby complete self-service and contact with others.

Treatment and rehabilitation of downs consists of the following procedures:

• Massages - muscular system, both the infant and the adult with this syndrome are underdeveloped. Special gymnastics helps to restore muscle tone and maintains them in normal condition. Special attention given to hydromassages. Swimming and water gymnastics improve motor skills, strengthen muscles. Dolphin therapy is popular when the patient swims with dolphins.
• Dietitian consultations - patients with trisomy have problems with being overweight. Obesity can provoke various disorders, the most common being disorders of the cardiovascular system and digestive tract. The dietitian gives recommendations on nutrition and, if necessary, prescribes a diet.
• Consultations of a speech therapist - for mosaicism, as well as for other types of the syndrome, disturbances in the development of speech are characteristic. Classes with a speech therapist will help the patient correctly and clearly express their thoughts.
• A special training program - children with the syndrome lag behind their peers in development, but they are trainable. With the right approach, the child can master the basic knowledge and skills.

Famous People with Mosaic Down Syndrome

Changes in the 21st chromosome lead to irreversible consequences that cannot be treated. But, despite this, among those born with trisomy there are artists, musicians, writers, actors and many other accomplished personalities. Famous people with a mosaic form of Down syndrome boldly declare their illness. They are a vivid example of the fact that, if desired, you can cope with any problem. The following celebrities have a genomic disorder:

• Jamie Brewer is an actress best known for her role in American Horror Story. The girl not only acts in films, she is also a model. Jamie walked the Mercedes-Benz Fashion Week show in New York.

• Raymond Hu is a young artist from California, USA. The peculiarity of his paintings is that he draws them according to the ancient Chinese technique: on rice paper, watercolor and ink. The guy's most popular works are portraits of animals.

• Pascal Duquinne - actor, winner of the silver award at the Cannes Film Festival. He became famous for his role in Jaco van Dormel's film Day Eight.

• Ronald Jenkins is a world famous composer and musician. His love for music began with a gift - a synthesizer received as a child for Christmas. To date, Ronald is rightfully considered a genius of electronic music.

• Karen Gafnii is a teaching assistant and an athlete. The girl is engaged in swimming and participated in the marathon on the English Channel. She became the first person with mosaicism to swim 15 km at a water temperature of +15°C. Karen has her charitable foundation, which represents the interests of people with chromosomal pathologies.
• Tim Harris is a restaurateur, owner of "the friendliest restaurant in the world." In addition to a delicious menu, Tim's place offers free hugs.

• Miguel Tomasin is a member of the Reynols band, drummer, guru of experimental music. The guy performs both his songs and covers of famous rock musicians. He is engaged in charity work, performs in centers and at concerts to support sick children.

• Bohdan Kravchuk is the first person in Ukraine with Down syndrome who entered the university. The guy lives in Lutsk, is fond of science, has many friends. Bohdan entered the East European National University named after Lesya Ukrainka at the Faculty of History.

As practice and real examples show, despite all the complications and problems of genetic pathology, with the right approach to its correction, it is possible to raise a successful and talented child.