Karyotype analysis to determine syndromes: Down, Klinefelter, Turner, etc. (Mon. Tue
Karyotype analysis to determine Down syndrome, Klinefelter syndrome, Turner syndrome
Down, Klinefelter and Turner syndromes are the most common chromosomal disorders. Therefore, from a prophylactic point of view, it is important to diagnose these diseases as early as possible by karyotyping and, in some cases, to carry out prenatal diagnosis.
Down syndrome (trisomy on chromosome 21) - one of the forms of genomic pathology, in which the karyotype is most often represented by 47 chromosomes instead of the normal 46, since the chromosomes of the 21st pair, instead of the normal two, are represented by three copies. There are two more forms of this syndrome: translocation of chromosome 21 to other chromosomes (more often to 15, less often to 14, even less often to 21, 22 and the Y chromosome) - 4% of cases, and a mosaic version of the syndrome - 5%. Down syndrome is not a rare pathology - on average, there is one case in 700 births; at the moment, due to prenatal diagnosis, the frequency of children born with Down syndrome has decreased to 1 in 1100. In boys and girls, the anomaly occurs with the same frequency. The probability of having children with Down syndrome increases with the age of the mother (after 35 years) and to a lesser extent with the age of the father. According to the literature data, the frequency of nondisjunction of the 21st chromosome in spermatogenesis, as well as in oogenesis, increases with age. After the accident at the Chernobyl nuclear power plant, an increase in the number of congenital pathologies was found in various regions of Belarus between 1986 and 1994, but it was approximately the same in both contaminated and clean regions. In January 1987, an unusual big number cases of Down syndrome, but no subsequent upward trend in incidence was observed.
Klinefelter syndrome occurs in 1 in 500 boys. Patients with classic version syndromes have a 47,XXY karyotype. Other karyotypes are also possible, and in 10% of patients mosaicism 46,XY / 47,XXY is detected, and more rare karyotypes are also found: 48,XXXY; 49.XXXXY ; 48,XXYY ; 49,XXXYY . The syndrome usually manifests itself in adolescence as a delay in sexual development. The penis and testicles are reduced, the physique is eunuchoid, infertility, gynecomastia, moderate mental retardation and antisocial behavior are characteristic. Sometimes testicular hypoplasia is the only sign of the disease in apparently healthy men. Patients are predisposed to diabetes mellitus, thyroid disease and breast cancer. The presence of at least two X chromosomes and one Y chromosome in the karyotype is the most common cause of primary hypogonadism in men. Methods for the treatment of infertility in Klinefelter's syndrome have not yet been developed. Testosterone replacement therapy is usually started at 11-14 years of age; with androgen deficiency, it significantly accelerates the formation of secondary sexual characteristics. In adult patients, libido increases during testosterone treatment. Gynecomastia may require surgery. Psychotherapy contributes to the social adaptation of patients with Klinefelter's syndrome and patients with other sex chromosome anomalies.
Shereshevsky-Turner syndrome or gonadal dysgenesis - This is a violation of the development of the sex glands caused by an anomaly of the sex chromosomes. During the division of the germ cells of the parents, the divergence of the sex chromosomes is disrupted, as a result of which, instead of the normal number of X chromosomes (and normally a woman has two), the embryo receives only one X chromosome. The set of chromosomes is incomplete. This syndrome occurs with a frequency of one in three thousand born girls. The development of the gonads is disturbed already in the early period of the development of the embryo. During puberty, secondary sexual characteristics do not develop (the mammary glands are underdeveloped, hair growth on the pubis and in the armpits is not expressed). There is no menstruation. One third of patients have malformations of other organs, as well as diabetes, inflammatory diseases of the colon, goiter and thyroiditis, gastrointestinal bleeding.
Syndrome X0-Shereshevsky-Turner syndrome. Syndrome XXY - Klinefelter's syndrome in neurology
Syndrome X0 due to a lack of genetic material located on the X chromosome. First described by N. A. Shereshevsky in 1925, and in 1938 by 1. Turner. It occurs with a frequency of 1: 2500-1: 3000 newborn girls.
Pathological studies indicate underdevelopment of the gonads, which are either completely absent, or have the form of connective tissue strands with remnants of ovarian tissue and interstitial cells. Often, malformations of the cardiovascular system are found (coarctation of the aorta, pulmonary artery stenosis, ventricular septal defect, non-closure of the ductus arteriosus), gastrointestinal tract, urinary system (cystic kidney, horseshoe kidneys).
Diagnose syndrome can be already in the neonatal period. Children are born with low weight and small stature, moderate swelling of the hands and feet can be observed for several months; low hair growth on the neck, a short neck with pterygoid folds running from the mastoid processes to the shoulders, or excessive mobility of the skin on the neck. Other developmental anomalies include epicanthus, fused eyebrows, ptosis, lagophthalmos or exophthalmos, hypertelorism, microphthalmos, eyelid colobomas, wide flat chest imitating widely spaced nipples, fusion of the vertebrae, clinodactyly, valgus curvature of the feet, malocclusion, skin and intestinal telangiectasias , osteoporosis.
On ophthalmic examination cloud-like opacities and a decrease in the sensitivity of the cornea, pallor of the optic nerve, narrowing of the arteries in the fundus, microphthalmos, cataracts are detected.
in neurological status usually no deviations are observed, with the exception of general muscle hypotension. Mental development at an early age is normal or its pace is somewhat slowed down.
On dermatoglyphic examination change of skin patterns of fingers and palms comes to light. An increase in the frequency of ulnar loops on the thumbs and forefingers is usually found. Distal axial triradius occurs in 50% of patients with Shereshevsky-Turner syndrome. More often than in healthy people, there is a transverse fold of the palm and a single fold on the fifth finger. Palmar patterns are very large distal loops or whorls with a large ridge count.
The complex of the indicated symptoms is an indication for the study of scrapings of the oral mucosa for sex chromatin. About 80% of patients with Shereshevsky-Turner syndrome are chromatin-negative, their karyotype is 45, XO. With deletions of Xq-, Xp-, as well as with a ring X-chromosome, XO/XX mosaccism, clinical signs are less pronounced than with XO syndrome. In scrapings from the mucosa, small Barr bodies are determined in a smaller amount than in normal girls.
Diagnosis verified by studying the karyotype of peripheral blood lymphocytes.
In young years syndrome should be differentiated from malnutrition of another etiology, hypothyroidism, congenital anomalies in the development of a non-chromosomal nature; with severe redundancy of the skin on the neck - from cutis laxa and Ehlers-Danlos syndrome.
Treatment of Shereshevsky-Turner syndrome symptomatic at an early age. In order to stimulate mental and motor development, cerebrolysin, aminolone, acephen, prephyson, B vitamins, massage, physiotherapy exercises are used.
Syndrome XXY (Klinefelter's syndrome)
Syndrome due to trisomy of the sex chromosomes due to the presence of an additional X chromosome. It occurs with a frequency of 1: 400-500 newborn boys. Described in 1942 by A. Klinefelter et al.
Pathomorphologically characterized primary gonadal dysgenesis. Histological examination reveals narrowing or obliteration of the seminiferous tubules, hyaline sclerosis, proliferation of Leydig cells. The non-obliterated tubules are filled with degenerative Sertoli cells.
characteristic feature syndrome in early childhood is a decrease in the size of the testicles and a change in their consistency (more dense or, conversely, softer). Already in the neonatal period, attention is drawn to the features of the child's physique - disproportionately long legs and arms, a narrow chest. Mental development is often normal. In a number of patients, changes in the eyes are described in the form of pigmentary degeneration of the retina and coloboma of the uveal tract.
Boys with Klinefelter Syndrome chromatin-positive. On dermatoglyphs, there may be a shift in the axial triradius, an increase in the atd angle, an increase in the frequency of arches on the fingers, and a tendency to a decrease in the ridge count.
Diagnosis verified by the study of the karyotype in peripheral blood lymphocytes, in which in most cases 47 chromosomes are detected due to the additional X chromosome. However, the number of X chromosomes can be more than 2. In such patients, all the symptoms of the disease are more pronounced, mental retardation is necessarily noted, the deeper, the more X chromosomes in the karyotype, there may be gigantism, acromegaly.
Syndrome at an early age diagnosed only with a screening study of sex chromatin.
Treatment at an early age, they are carried out only in cases that occur with a lag in mental development. Prescribe drugs that stimulate the function of the central nervous system (aminolon, cerebrolysin, B vitamins), conduct speech therapy and pedagogical classes, purposefully forming higher cortical functions.
Syndrome XYY. The 47,XYY karyotype occurs among newborn boys with a frequency of 1:250-500 and is most often not accompanied by a pathological phenotype. At an early age, developmental features are not found. May be an accidental karyooptic finding.
Polysomy X syndrome. It most commonly occurs as trisomy X (47, XXX) and may not be associated with an abnormal phenotype. If the number of X chromosomes is more than 3, mental retardation and gonadal dysgenesis are characteristic, the more pronounced, the more additional X chromosomes.
Question on the analysis of the karyotype: disease or down syndrome?
Ulya2: The question of the karyotype and types of Down syndrome is considered and discussed in detail here: http://downsyndrome.borda.ru/?1-1-40-00000031-000-0-0-1230646216 Moderator I don’t know where you can ask this question decided here , is it possible to determine the disease or down syndrome by analyzing the karyotype? Our cardiologist offered to apply for disability due to a large heart defect, adding at the same time “especially since you have Down syndrome” when I said that they don’t give disability with a syndrome, I answered, you will make an analysis, you will find out you have a disease or syndrome. With the analysis of the karyotype, we had a problem, they did it for 35 days, they explained that at first there was no growth, and then it grew. I don’t know how in genetics, but in my opinion, if something should grow, then immediately, especially from the forum I learned that the analysis done from 4 days to two weeks, maybe I'm wrong?
Mary: The word "syndrome" means a set of signs or characteristics. Down syndrome, as shown in 1959 by the French scientist Jerome Lejeune, is a genetic condition that exists from the moment of conception and is determined by the presence of an extra chromosome in human cells. This condition was named after the English physician John Langdon Down, who first described its symptoms in 1866. The human body is made up of millions of cells, each of which usually contains 46 chromosomes. Chromosomes are arranged in pairs - half from the mother, half from the father. In people with Down syndrome, an extra chromosome is present in the 21st pair, as a result of which, 47 chromosomes are found in the cells. In this case, the parents, as a rule, have a normal genotype. click here Down's disease is only in the minds of incompetent doctors. click here Read here, this topic has been discussed elsewhere, but it's hard to find.
Ulya2: Mary writes: Down's disease is only in the minds of incompetent doctors. I also thought so, but after talking with the doctor, I began to doubt, especially after her words “I’m a doctor, I know better” and now I don’t know if we should retake the analysis to find out for sure whether we have a syndrome or a disease.
Hope: As geneticists told me, before the general check of karyotypes, the syndrome was written in the presence of simply similar features (outwardly, physiological, suitable for the syndrome), and if it was confirmed by analysis of the karyotype, they put the disease. Gradation exists only in forms - complete trisomic, transgenic and mosaic. Although our miracle doctors, in addition to the syndrome and illness, can also distinguish “downism” The girls on the forum wrote that even neurologists sin with this. So any of the mothers who have encountered this problem, I'm afraid, knows much more than any doctor.
G-NA85: Hope writes: Although our miracle doctors, in addition to the syndrome and illness, can also distinguish "downism" Yes, the neurologist wrote Apollinaria in the card. I made him remake Down Syndrome. It sounds more beautiful that way. Down's disease is not. There is Down Syndrome - trisomy or just external signs of diabetes - without trisomy, but an experienced doctor writes Down Syndrome. External signs are not taken into account at all - if they are not supported by three chromosomes. ula2 says: Tvetila will make an analysis to find out if you have a disease or a syndrome. What kind of STUPID doctors are, just oaks, well, take it, aunt doctor, read a book, before polluting the air with nonsense, they don’t sculpt nonsense, only poor mothers are forced to waste money on tests and inject the child in vain.
Hope: G-NA85 writes: Down's disease is not. There is Down Syndrome - trisomy or just external signs of diabetes - without trisomy, but an experienced doctor writes Down Syndrome. External signs are not taken into account at all - if they are not supported by three chromosomes. Tanya, well, you and I (and other mothers of our children) know this, but for many doctors, as my mother-in-law put it when I asked what teaching methods are available (she is a teacher): “I have nothing to study this problem, and no time" So really, OAKS
OlgaLD:ulya2 Questions of terminology, don't worry. Good luck!
klimenko: Recently, I went through a commission with Marusya and the pediatrician asked me if the child has Down syndrome or Down syndrome? and it is useless to deal with them?
OKS: Girls! And our diagnosis is simply “trisomy on chromosome 21”. Agree, it sounds neat.
lyusya: Girls, and now, diagnoses are written under numbers. Down's syndrome is coded like this - Q 90. How beautiful it sounds, right?
Mariyka: And in our country, doctors are at a loss: write syndrome or illness. Who wants to seem smart in this matter writes "illness", and those who already know - "syndrome". Who is into what. They need to come to terms with each other. Sometimes you just want to conduct an educational program especially for them.
Laura: Remember where I read. but the bottom line is that if it's just a chromosome set and external signs, then this is a syndrome. And if there are also malformations, mental retardation, then already a disease. Doctors also often ask us: what do you have, a syndrome or an illness. And they write everywhere: illness. Even in the conclusion of geneticists it is written: the diagnosis is Down's disease (translocation variant). I quote verbatim.
Laura: Here's another found. Textbook for medical schools, author Bisyarina V.P., year of publication 1981 "Children's diseases and child care." Here they write about Down's disease. Maybe that's why all the doctors say that? We studied from this textbook (or from the same ones published by the Medicina publishing house).
G-NA85: Laura writes: . And if there are also malformations, mental retardation, then already a disease. And in my opinion, all of our children have some malformations and MR is mostly in a mild form. The vices are also different for everyone, but some small things everyone will scrape together. Therefore, it is still correct - DOWN SYNDROME, not a disease. The disease is the old fashioned way and only in the territory of the former Soviet Union, where a doctor is too lazy to pick up a book. And really, what is there to learn? I have a diploma, they gave me a white robe.
Mary: Syndrome - definitions on the Internet: Syndrome (σύνδρομον, σύνδρομο, "equal, in agreement") - a combination of symptoms. en.wikipedia.org/wiki/Syndrome is a natural combination of symptoms due to a single pathogenesis; is considered as an independent disease (for example, Meniere's syndrome) or as a stage. www.medotvet.ru/dict/zabol/glossary/homemed_glossary_s.php a natural combination of signs (symptoms) that have general mechanism occurrence. dic.paludarium.ru/017.htm (Greek syndrome - a confluence of signs of a disease; a synonym for a symptom complex) - a set of symptoms united by a single mechanism of the disease; sometimes referred to by this term. www.magalif.ru/index.php complex of symptoms. www.infospid.ru/index.php a condition that develops as a consequence of a disease and is determined by a combination of clinical, laboratory, and instrumental diagnostic features. www.ssmu.ru/office/sibcem/glossary/protocols.shtml set of symptoms characteristic of a given disease. zoolife.com.ua/pageid1006.html That is, the symptom and the disease are in one bundle. The time comes and it still becomes, as they call it, a syndrome, a disease - trisomy21 more precisely.
Laura: OKS, about translocation is very well written in some topic by Tatiana Spomer. Even photos of chromosomes. In short, this is when there are not 3 21st chromosomes, but 2, but one of them is attached to some other pair. Or they have grown together, forming one anomalous one. So it is with our Arseniy, the total number of chromosomes is 46. And how is it written in your analysis? Or did you not?
OKS: Laura We did. We have 47 unfortunately. I was just curious about translocation. And it is written like this: karyotype: 47,XX, +21.21ps+. Here. Conclusion: trisomy on chromosome 21.
Laura: OKS why "unfortunately"? We also have a syndrome, despite 46 chromosomes. Typical appearance, heart disease, developmental delay. And if it’s more or less clear with your diagnosis that the chromosomes didn’t come apart, then we don’t understand how one wormed its way into another pair. Did you look at the seagulls and stay? How does it happen that the chromosomes “run away”, I wonder if the experts have an answer?
lilka: Yesterday they called a doctor to the house, a Russian old woman came. We immediately told her that the child had Down syndrome. She agreed, said: “Yes, you have a syndrome, not Down himself. Down is much heavier." At least we had some fun.
Irene: We were told at the Institute of Pediatrics: “Down’s disease is when almost all organs are affected, Down syndrome is a small part.” When we arrived, they immediately asked, “Do you have a disease or a syndrome?”
Irene: OKS They meant accompanying "sores".
Ulya2: I can't find anywhere what 13 means in our analysis result Karyotype: 47,XX,+21 maybe someone here knows?
G-NA85: Maybe the arm of chromosome 13 fell on the arm of 21 and they did not separate (this is a primitive explanation). I once asked a geneticist about these shoulders, although Apollinaria has a different analysis. It's like a translocation. You need to consult.
Ulya2: I was told that it looks like a tralocation, but in the conclusions it is written in one: The karyotype is abnormal, unbalanced. Trisomy on a chromosome 21. Down's syndrome. in another: Trisomy on chromosome 21. I already regret that I passed the analysis for the second time, I found myself an extra headache. The first time we passed in our city, because. the genetic center appeared recently, there was a hope that they were mistaken, and the geneticist was not very smart, he offered to give up her daughter. So we decided to take it again in Novosibirsk, when we went for an operation, this figure appeared there 13
Assol: Ulya, in our karyotype there were numbers in square brackets, but we have a mosaic, and it was like 46XY(15), 47XY(20). As far as I understood, the number in brackets meant how many cells with such a set were found, because The geneticist said we're about 50/50. Maybe you have something similar too?
Ulya2: so we have a possible mosaic? Probably you need to call the Novosibirsk laboratory, they didn’t answer the email, but I don’t want to meet with our geneticist
Svetlana:ulya2 writes: Probably need to call the Novosibirsk laboratory, they didn’t answer the email I don't think they answer the phone either. This is strictly prohibited - medical secrecy is not an abstract concept at all. They have the right to provide such information only in person. At one time, we were told by phone only that the analysis was already ready and we could come and pick it up.
Assol:ulya2 writes: Does this mean we have a mosaic? As far as I understand, in your karyotype it says only about 47 chromosomes, but nothing about 46. Then it is unlikely that there is a mosaic, with a mosaic there are 46 chromosomes, and 47. Maybe 13 in your case - that 13 cells were checked. Or maybe it means something else
G-NA85: It doesn't look like a mosaic, there really should be 46 chromosomes written. Ask any other geneticist, not yours. We were told that this is a transla- tional form when we described the possible options. Although Apollinaria has a simple trisomy, but according to our (parental) analyzes, there should be a translocation. In fact, it doesn't matter at all. It only interested me for the first two months, and then I gave up on these chromosomes, well, them. Still they are not visible.
Alexa and Lyosha: G-NA85 Did you have tests before the birth of Apollinaria or after? We think about the next child and don't know what to do. Although after everything that happened to us (we were observed by geneticists throughout the pregnancy: a triple test, amniosynthesis, ultrasound - everything is fine), it is hard to believe that they will help us in any way.
Lena S.: Alexa and Lyosha writes: Although after everything that happened to us (we were observed by geneticists throughout the pregnancy: a triple test, amniosynthesis, ultrasound - everything is fine), it is hard to believe that they will help us in any way. Excuse me, but what, the amnio did not show the presence of an extra chromosome? Or did the cells miss? Indeed, who can then guarantee something.
Alexa and Lyosha: Lena S. I was told only after the birth of Lyosha that the reliability of the analysis for amniocinthesis is about 75% (part of the amniotic fluid may not contain fetal cells), and that a study at the 10th week of pregnancy is more reliable - a biopsy of the chorion, but there is also reliability 98%. And where is the guarantee that you will not fall into 2%?! Moreover, we did the amniocentesis on our own initiative, only because I was 35 years old, the doctors were a little perplexed, the triple test was good, Voevodin himself did not find any pathologies on ultrasound. And now I think, that's what it was - a premonition? No, I just wanted to do everything right, as it is written in the books. But now I know that I did everything possible to prevent this situation. A child from God, that's the whole explanation!
Assol: Alexa and Lyosha It turns out that the amnio predicted the birth of a girl for you? After all, if it was not the cells of the child that got into the analysis from the amniotic fluid, then these were your cells, there should have been a set of XX. Did you see the boy on the ultrasound?
Alexa and Lyosha: Ассоль We had an amniocentesis in order to identify genetic pathologies, and not to find out the sex of the child. The topic of the sex of the child with the geneticist was not discussed at all. We found out that we will have a boy at 24 weeks pregnant, 4 weeks after the amnio.
Assol: Alexa and Lyosha writes: We had an amniocentesis in order to identify genetic pathologies, and not to find out the sex of the child. This is understandable, just the sex of the child in this analysis is determined automatically when the chromosomes are considered. But apparently they didn't tell you, and you didn't ask.
anonymous: hello! Tell me please. we did a karyotype analysis and the result is: 47,Xy,+21 and additionally: Q90.0 Trisomy 21, Meiotic nondisjunction
OlgaLD: anonymous Hello, welcome to the forum! This means that your child has Down syndrome, the usual form is trisomy 21. This is indicated by the code Q90.0. Meiotic nondisjunction corresponds to normal trisomy. tourist writes: Karyotype 47,xx; +21, that is, an additional 21 chromosome was found in all the examined cells. And the diagnosis is Q 90.0 (otherwise they say trisomy 21 - meiotic non-disjunction), if Q 90.1 is written, then Trisomy 21, mosaicism (mitotic non-disjunction) Q 90.2 Trisomy 21, translocation http://www.downsyndrome.borda.ru/?1-9-0-00000099-000-120-0 Translocation and mosaicism occur each in 4-5% of cases, the remaining 90%+ are common trisomy. The karyotype is represented by 47 chromosomes instead of the normal 46, since the chromosomes of the 21st pair, instead of the normal two, are represented by three copies (trisomy). Hence the number 47 in your analysis and the addition of "+21". In other words, "trisomy 21". Meiotic means what happened during meiosis, meiosis means cell division. In other words, Down syndrome is obtained when chromosomes do not diverge during meiosis, cell division, i.e. present at conception. Seems to have explained everything. Welcome to the forum! Read these pages: http://sunchildren.narod.ru/whatis.html http://sunchildren.narod.ru/whatdo.html http://sunchildren.narod.ru/startwith.html Write where you are from, you can find fellow countrymen who will help you get comfortable with the diagnosis and find answers to your questions.
KarinaSH: Folks, I was given a lecture today at the RC that like disease D and DM are different things, so if there is no heart defect, then it is DM, and here I read a DB, How!
OlgaLD: KaRinaSH You are not the first, you are not the last, you can read this topic, but in general this info from “specialists” often pops up on our forum
Tatyana A: And on our analysis paper it says 46, xx, der (14:21) (g10:10) +21 translocation
OlgaLD: Tatyana A Well, you have a translocation form, which is rarer
wap.downsyndrome.borda.ru
karyotype down syndrome
Clinical diagnosis of Down syndrome usually presents no difficulty. However, karyotyping is necessary to confirm the diagnosis and provide a basis for genetic counseling. Although differences in specific karyotype variants responsible for Down syndrome usually have little effect on the patient's phenotype, they are significant in determining the risk of recurrence.
Trisomy 21 in Down syndrome. Approximately 95% of all Down syndrome patients have trisomy 21, caused by meiotic nondisjunction of chromosome 21, as discussed in the previous chapter. It has already been noted that the risk of having a child with trisomy 21 increases with the age of the mother, especially after 30 years. The meiotic error responsible for trisomy usually occurs during maternal meiosis (about 90% of cases), predominantly in the first division, but about 10% of cases occur in paternal meiosis, usually in the second division.
Robertsonian translocation in Down syndrome. About 4% of Down syndrome patients have 46 chromosomes, one of which is a Robertsonian translocation between chromosome 21q and the long arm of one of the other acrocentric chromosomes (usually chromosomes 14 or 22). The translocated chromosome replaces one of the normal acrocentric chromosomes, and the karyotype of a patient with a Robertsonian translocation between chromosomes 14 and 21 is 46,XX/XY,rob(14;21)(ql0;ql0),+21.
Such chromosome can also be defined as der(14;21), in practice both nomenclatures are used. In fact, patients with a Robertsonian translocation involving chromosome 21 trisomy for genes located in the 21q long arm.
Unlike standard trisomy 21, translocation Down syndrome shows no association with maternal age, but has a relatively high risk of recurrence in families if one of the parents, especially the mother, is a carrier of the translocation. For this reason, karyotyping of parents and possibly other relatives is important for accurate genetic counseling.
carriers Robertsonian translocation, which includes chromosomes 14 and 21, has only 45 chromosomes; one 14 and one 21 are missing and replaced by a translocated chromosome. Theoretically, six types of gametes are possible, but three of them cannot lead to viable offspring. The three types of gametes are viable, normal, balanced, and unbalanced, having both translocated and normal chromosome 21. In combination with a normal gamete, this can lead to the conception of a child with translocation Down syndrome.
Theoretically, these three types gametes are produced in equal amounts, so the theoretical risk of a child with Down syndrome should be 1 in 3. However, extended population studies have shown that unbalanced chromosome sets appear in only 10-15% of the offspring of mothers and only a few percent of the offspring of fathers who carry translocations that include chromosome 21.
21q21q translocation in Down syndrome. Chromosomal translocation 21q21q - a chromosome formed from two long arms of chromosome 21; occurs in a few percent of patients with Down syndrome. They are thought to appear as isochromosomes rather than Robertsonian translocations. Most of these cases occur post-zygotically, so the risk of recurrence is low. However, it is especially important to make sure that the parent is not a carrier (possibly mosaic) of this translocation, since all gametes of the carrier of such a chromosome must also contain the 21q21q chromosome, with a double dose of chromosome 21 genetic material, or not have chromosome 21 at all.
Potential offspring therefore inevitably has either Down's syndrome or non-viable monosomy 21. Mosaic carriers have an increased risk of recurrence, so prenatal diagnosis is necessary in all subsequent pregnancies.
Mosaic Down Syndrome. About 2% of patients with Down syndrome are mosaics, usually with populations of normal cells and with trisomy 21. The phenotype may be milder than typical trisomy 21. In general, there is wide variability in the phenotypes of mosaic patients, probably reflecting different proportions of trisomy cells in the embryo at early stages of development. It is possible that patients with established mosaic Down syndrome only reflect clinically more severe cases, since mild cases are less likely to be karyotyped.
Partial trisomy 21 in Down syndrome. Very rarely, Down syndrome is diagnosed in patients with trisomy only on part of the long arm of chromosome 21, and even more rarely, patients with Down syndrome are identified without a cytogenetically visible chromosomal abnormality. Such cases are of particular interest because they may indicate which region of chromosome 21 is likely to be responsible for specific components of the Down syndrome phenotype and which regions may triple without causing phenotypic manifestations.
Although chromosome 21 contains only a few hundred genes, attempts to match the triple dose of specific genes to specific aspects of the Down syndrome phenotype have so far had limited success. Most notable was the identification of an area critical for heart defects, seen in approximately 40% of patients with Down syndrome. The search for specific genes that are essential for the manifestation of the Down syndrome phenotype, among those randomly located next to them on chromosome 21, - the main task modern research, especially on mice as a model.
Potentially promising direction- study of genetically engineered mice with an extra dose of genes from human chromosome 21 (or even with a complete copy of chromosome 21). Such mice may exhibit phenotypic abnormalities in behavior, brain function, and heart formation.
A karyotype is a set of features of a chromosome set (number, size, shape of chromosomes) characteristic of a particular species.
The study of all elements of the human karyotype is carried out using the method of special staining and subsequent examination of chromosomes in a light microscope. This method helps to see the size and shape of chromosomes, 
their structure. Diseases accompanied by pathological changes in the karyotype are called chromosomal. Example
chromosomal disease - Down's syndrome. The causes of Down's syndrome lie in the intrauterine formation of fetal chromosomal pathology. So, if the normal karyotype of a healthy person consists of 46 chromosomes, then with Down syndrome it is formed by 47 chromosomes, an additional chromosome responsible for the disease is found in 21 pairs.
An abnormal karyotype is found in about 1% of all newborns. The consequences of such anomalies can range from death to mental retardation and mild anomalies. Cases of abnormal chromosome number increase with maternal age. The age of the expectant mother also affects the risk of developing Down syndrome in a child: if under the age of 35 this risk is 1 in 1000; then at the age of 40 years, the risk increases to 1 in 214; over the age of 45, the risk increases to 1 in 19.
There are many options for deviations from the norm. To date, the following anomalies have been identified:
This happens already at an early stage of embryonic development. One of the reasons for deviations is a violation of spermatogenesis, some of the disturbed spermatozoa are still involved in the fertilization of the egg and, therefore, may be the cause of the formation of an embryo with a disturbed karyotype.
The main unfavorable factor in the appearance of deviations is poor ecology, which provokes chromosomal mutations. All these anomalies are inherited.
There is currently no content categorized by this term.
Mosaic form of Down syndrome: how to determine
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
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 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:
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 present in all cells, since during meiosis the division of paired chromosomes is disrupted in parental cells. 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:
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.
The development of a genetic disease is 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. It has a positive prognosis, since 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.
The main physical symptoms of the disease:
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 manifestations 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:
Upon further examination, the following problems are revealed:
In addition to external symptoms, the syndrome also has internal disorders:
The above symptoms require constant treatment to maintain the normal state of the body. Birth defects are the cause short life 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:
- Abnormal structure of the skull.
- Congenital defects of the oral cavity.
- Additional skin folds.
- Pathologies of the development of the musculoskeletal system
- Chest deformity.
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 relate to the structure of the cranium and the 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.
A person with this disease resembles a representative of the 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.
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".
This violation occurs in 40% of cases. Underdeveloped cartilages form the wrong auricle. Ears can be protruding in different directions or located below eye level. Although the defects are cosmetic, they can cause serious hearing problems.
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.
Occur due to a violation of intrauterine development of the fetus. The connective tissue of the joints and some bones do not have time to fully form before birth. The most common anomalies are: short neck, increased joint mobility, short limbs, and deformed fingers.
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 deformity, in which there is a funnel-shaped depression in the solar plexus area. 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.
The syndrome has several types, consider them:
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:
In addition to the complications described above, trisomy is characterized by thyroid problems, 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 for diagnosing trisomy:
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.
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.
- 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.
- Shereshevsky-Turner syndrome
- Edwards syndrome
- de la Chapelle syndrome
- congenital hypothyroidism
- Other forms of chromosomal abnormalities
- Massages - the muscular system, both of an infant and an adult with this syndrome, is underdeveloped. Special gymnastics helps to restore muscle tone and maintain them in a normal state. Particular attention is paid 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 the 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.
- Timely treatment of any diseases and a healthy lifestyle. Increased activity improves blood circulation, protecting the eggs from oxygen starvation.
- Proper nutrition and normal weight. Vitamins, minerals and other nutrients not only strengthen the immune system, but also support hormonal balance. Excess weight or excessive thinness disrupt the hormonal balance, and provoke failures in the maturation and development of germ cells.
- Preparation for pregnancy. A couple of months before the planned conception, you need to consult a gynecologist and start taking vitamin and mineral complexes. Particular attention should be paid to folic acid, vitamins B and E. They normalize the functioning of the genital organs and improve metabolic processes in sex cells. Do not forget that the risk of giving birth to a child with abnormalities increases in couples where the age of the expectant mother is more than 35 years old, and the father is more than 45.
- prenatal diagnosis. Analyzes, screenings and a number of other diagnostic procedures performed during pregnancy allow you to identify serious disorders in the fetus and make a decision on further gestation or abortion.
- 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 own 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. Bogdan entered the Eastern European National University named after Lesya Ukrainka at the Faculty of History.
- elderly parents, mother over 35 years old, father over 45 years old;
- too early, before 18 years, the age of the mother;
- married relatives.
- flat face shape in 90% of cases;
- thickened size of the skin neck fold;
- short head shape;
- slanted eye type;
- "Mongolian fold", located in the corner of the eye, capable of covering the lacrimal tubercle.
- reduced level of muscle tone;
- increased activity of mobile joints;
- the hand is short and wide;
- flat nape;
- arched sky;
- deformed shape of the auricles;
- large folded nose;
- transverse fold on the palm (45% of children);
- modified chest (keeled);
- located on the edge of the iris, age spots.
- many congenital heart diseases, defects of the interventricular, interatrial septum, anomaly in the development of blood vessels, an unclosed atrioventricular canal;
- possible sudden cessation of breathing in a dream, due to the peculiarities of the tongue and pharynx;
- defects from the visual system, strabismus, cataract, glaucoma;
- anomalies in the development of the hearing aid;
- thyroid disease;
- all kinds of pathologies from the gastrointestinal tract;
- damage to the musculoskeletal system, joint dysplasia, lack of ribs, crooked fingers, deformed chest;
- insufficient development of the kidneys.
- Down syndrome on ultrasound can be diagnosed in the first 12 weeks of pregnancy by identifying specific signs. A test for Down syndrome is also performed, in which the thickness of the collar space in the fetus is measured: if it exceeds 2.5 mm, there is a risk of developing the disease. On ultrasound, Down syndrome can also be determined by the presence or absence of the nasal bone in the fetus.
- To diagnose Down syndrome, a biochemical study of the blood of a pregnant woman for up to 13 weeks (hCG) is carried out. At 16-18 weeks of pregnancy, a triple test is performed: ACE, hCG, E3.
If, according to the results of the tests, a high risk of trisomy is established, 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 of 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:
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 in the late stages of embryonic development.
Who to contact?
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:
Patients are shown restorative therapy, psychostimulants, neurometabolic and hormonal drugs are often prescribed. Regular intake of vitamins is also necessary. All drug therapy is combined with medical and pedagogical correction. Congenital pathologies and complex diseases require surgical intervention.
Prevention
To date, there are no reliable methods for the prevention of genetic diseases. Prevention of mosaic Down syndrome consists of the following recommendations:
But even the implementation of all preventive measures cannot give a 100% guarantee of the birth of a completely healthy baby. Trisomy is a random genetic anomaly that no woman is immune from.
Mosaic Down syndrome has a more positive outcome, in contrast to the classical form of pathology. The prognosis is due to the fact that healthy cells partially compensate for the genetic defect. But the child will still have external signs of trisomy and a developmental delay characteristic of it. But the survival rate of such patients is much higher, they are less likely to have malformations that are incompatible with life.
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:
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.
The human genome consists of 46 chromosomes arranged in 23 pairs. Of these, 44 are somatic, that is, they are responsible for the structure and characteristics of the entire human body. And only one pair of chromosomes carries information about its gender and determines the differences between men and women.
Both sex chromosomes of women are identical in structure and are designated in genetics by the letter X. And in men, this pair is represented by different chromosomes - X and Y.
Klinefelter syndrome: karyotype
Klinefelter's syndrome is considered such a change in the chromosome set, in which one or more X chromosomes are added to the XY karyotype. Accordingly, only carriers of the Y chromosome, that is, men, suffer from this disease.
A person with Klinefelter's syndrome has a chromosome set that differs from the norm by only one pair of chromosomes - just the one that is responsible for sexual characteristics.
For clarity, we tried to depict the karyotype of a patient with Klinefelter's syndrome in the figure:
Variety of options
Klinefelter's syndrome can be represented by different cytogenetic variants, which also determine the difference in the severity of symptoms and the tactics of managing patients.
The origins of the disease
The causes of the appearance of Klinefelter's syndrome lie in the non-disjunction of chromosomes during cell division.
According to statistics, a third of patients receive an extra chromosome from the father's sperm, and the other two-thirds from the mother's egg.
Risk factors for the onset of this disease are traditionally considered viral infections, disturbances in the functioning of the immune systems of the parents and the late age of the mother.
Establishing diagnosis
When the doctor can rely on the level of hormones in the blood test, the results of the spermogram, ultrasound of the scrotum and testicular biopsy. But the diagnosis can be finally confirmed only on the basis of a blood test for a karyotype characteristic of Klinefelter's syndrome.
To do this, leukocytes isolated from the blood are placed in a nutrient medium and then examined for the presence of a chromosomal abnormality in their DNA.
A modern blood test allows you to accurately differentiate any genetic disease and with a 100% probability to distinguish, for example, a syndrome from a syndrome even at the stage of pregnancy. For this, cells of the embryo or amniotic fluid are taken.
In developed countries, many chromosomal anomalies, including Klinefelter's syndrome, are detected even during pregnancy, as women planning motherhood at a later age try to eliminate the risk of having a sick baby as much as possible.
In the US, in the presence of such an anomaly in the unborn child, about half of women choose to terminate the pregnancy. In Russia, karyotyping analysis is not widely practiced, it is carried out only if, based on the results of screening of a pregnant woman, there are suspicions about the presence of genetic abnormalities in the fetus.
In many cases, the syndrome is detected much later.- upon occurrence characteristic features during growing up.
Despite the successes of modern medicine, about half of the cases of Klinefelter's syndrome remain generally unrecognized, although patients go to doctors with complaints of breast enlargement, erectile dysfunction and infertility.
Trisomy is the presence of three homologous chromosomes instead of a normal pair.
The most common in humans is trisomy 16 (more than one percent of pregnancies). However, the consequence of this trisomy is a spontaneous miscarriage in the first trimester.
Schematic representation of the karyotype of a man suffering from Down syndrome. Nondisjunction of G21 chromosomes in one of the gametes resulted in trisomy on this chromosome.
Among newborns, trisomy on the 21st chromosome, or Down syndrome, is the most common (2n + 1 = 47). This anomaly, named after the physician who first described it in 1866, is caused by nondisjunction of chromosome 21. Its symptoms include mental retardation, decreased resistance to disease, congenital heart anomalies, a short stocky body and thick neck, and characteristic folds skin over the inner corners of the eyes, which creates a resemblance to representatives of the Mongoloid race.
Other cases of autosome nondisjunction:
Trisomy 18 (Edwards syndrome)
Trisomy 13 (Patau syndrome)
Trisomy 16 miscarriage
Trisomy 9 (the frequency of detection of trisomy 9 among spontaneous abortions is 1:1000 pregnancies. Almost all conceptions end in fetal death of the carrier of extra chromosome 9. Life expectancy does not exceed three months and two weeks)
Trisomy 8 (Varkani syndrome)
Down syndrome and similar chromosomal abnormalities are more common in children born to older women. The exact reason for this is unknown, but it seems to be related to the age of the mother's eggs.
Cases of nondisjunction of sex chromosomes:
XXX (women are outwardly normal, fertile, but mentally retarded)
XXY, Klinefelter's Syndrome (males with some secondary female sex characteristics; infertile; ovaries poorly developed, little facial hair, sometimes mammary glands develop; usually a low level of mental development)
XYY (tall men with different levels of mental development;)
tetrasomy and pentasomy
Tetrasomy (4 homologous chromosomes instead of a pair in the diploid set) and pentasomy (5 instead of 2) are extremely rare. Examples of tetrasomy and pentasomy in humans are the XXXX, XXYY, XXXY, XYYY, XXXXX, XXXXY, XXXYY, XYYYY, and XXYYY karyotypes.
Causes of Down syndrome
Down syndrome is a genetic disease associated with the abnormal development of 21 chromosome pairs. Down syndrome outwardly shows signs in the form of slanting eyes, a flat face shape, a single transverse fold in the palm of the hand, short stature, a large tongue, etc.
Down's syndrome disease occurs due to the tripling of chromosome 21. The risk of Down syndrome in an unborn child increases when the mother's age is over 35 and the father's age is over 45.
man with down syndrome
Down syndrome was first described by English doctor John Langdon Down in 1866. He characterized the disease as mental retardation in combination with certain external manifestations. From the point of view of genetics, the characteristics of the disease were determined by Jerome Lejeune in 1959.
In women and men, Down syndrome manifests itself equally in equal parts. In case of Down syndrome, treatment should be directed towards neuropsychic rehabilitation, treatment of concomitant diseases, malformations, and also include social adaptation of such people.
Why disease occurs
The cells of a healthy human body have 23 pairs (46) of chromosomes. Each of them contains a certain proportion of genetic information, and each has an impact on the development of a certain characteristic of the organism. Doctors consider it necessary to number pairs of chromosomes from 1 to 23. Down syndrome has the following reasons: when 21 chromosome pairs are tripled, the disease begins to develop. A patient with Down syndrome has not two, but three chromosomes out of 21 pairs.
Down syndrome is most often expressed in the form of a standard trisomy, when chromosome 21 is completely tripled in all cells of the body. This form of the disease occupies 94% of all cases. About 4% of cases are occupied by a form of translocation, displacement of 21 chromosome pairs to the remaining chromosomes.
The mosaic form of Down syndrome is the rarest form of the disease (about 2% of all cases). With it, the tripled 21 chromosome is found only in some cells of the human body. A sick person, with this form, has a normal appearance, a developed intellect, but he can have children with Down syndrome.
Mosaic Down syndrome in newborns will be expressed by a slight developmental lag from their peers, and, as a rule, doctors cannot immediately determine the cause of the lag. Adolescents in appearance may have similarities with the appearance of a diagnosis of Down syndrome, but despite this, it is excellent to study at school at the level of peers. It is quite difficult to confirm the diagnosis in the mosaic form of Down syndrome, since only 10% of the cells out of the total number have a trisomic form of chromosome 21. A blood test for Down syndrome involves donating blood to large quantities on the karyotype - only in this case an accurate diagnosis is possible.
Video: Down syndrome
Mosaic Down's syndrome during pregnancy is very problematic to determine, since most fetal cells will be endowed with the properties of a conventional karyotype. Down syndrome in the trisomic form makes men infertile, and the mosaic form makes the function of childbearing possible, but born children in 98% of cases will be endowed with Down syndrome. Unfortunately, with a diagnosis of Down syndrome, in all its forms, it is almost impossible to give birth to healthy offspring.
Most often, Down syndrome can develop due to:
As the age of parents increases, there is a high risk of Down syndrome in their future children. Since in the process of aging the process of formation of female germ cells and in 25% of cases of male germ cells is disrupted. Age-related processes affect the division and maturation of germ cells, there is a risk of getting more chromosomes during maturation than necessary. And if this “special” cell takes part in fertilization, the resulting embryo will have 23 pairs of chromosomes and + 1 more, which will affect its further development and provoke Down syndrome.
Symptoms of the disease
The most common signs of Down syndrome in newborns are:
Upon further examination, children with Down syndrome will have the following signs:
In children with Down syndrome, symptoms from the internal organs may be as follows:
You can make a final diagnosis by performing an analysis for Down syndrome, while examining the chromosome set in the baby. Down syndrome in a child leads to a lag in mental and physical development, but despite this, children remain affectionate, attentive, obedient, patient. People with Down syndrome are 20 cm below normal in height, and the degree of their intellectual development depends on the time of onset and the volume of rehabilitation procedures.
Diagnosis of the disease
If the signs of Down syndrome on fetal ultrasound are confirmed, and the biochemical analysis of pregnant women for Down syndrome is positive, you should consult a geneticist for advice. He will prescribe additional examinations: analysis of the tissues of the membranes of the fetus, amniocentesis. This procedure involves taking amniotic fluid for analysis by piercing the anterior wall of the abdomen in order to examine the chromosome set of cells of the unborn baby.
To date, chorionbiopsy and amniocentesis are the most accurate methods for diagnosing possible abnormalities in the development of the fetus. However, this method of research is associated with some risk for both the mother and the child. There is a risk of abortion, injury to the fetus, development of bleeding, violation of the integrity of the tissues of the internal organs of the pregnant woman.
Treatment and prognosis of the disease
Many are concerned about the question of how many people live with Down syndrome. With a diagnosis of Down syndrome, life expectancy will be no more than 40-50 years. To date, medical science has not found a cure for this chromosomal disease. Although concomitant diseases such as congenital heart disease are successfully overcome, thereby prolonging the life of people with Down syndrome.
A characteristic feature in children with Down syndrome is a delay in the development of the central nervous system. Therefore, in the first trimester of pregnancy, mothers are recommended to take folic acid, as it reduces the risk of developing serious pathologies from the nervous system in Down syndrome, and will also make rehabilitation procedures after childbirth more effective.
Video: children with Down syndrome in schools and kindergartens
The treatment process for children should consist of social support and rehabilitation courses. The upbringing and education of children with Down syndrome should reveal the main goal - the ability to adapt in the family and society.
In order to improve and accelerate the process of adaptation of such a child in society, to prepare him for a meeting with the outside world, it would be appropriate group lessons. It is not necessary to protect the child from being in a children's team ( Kindergarten, school), being among peers, a child with Down syndrome quickly gets used to the world around him.
Such "special" children can study in specialized schools, or they can attend regular schools. educational establishments- this will only improve the social preparation of the child.
In special rehabilitation centers psychologists and speech therapists have developed the necessary programs for the development of the personality of a down child. With a properly planned approach and training, sick children will eventually be able to master the same skills and abilities as healthy ones.
Special medications - nootropics, which stimulate the development of the brain and nervous system, can increase the effectiveness of rehabilitation procedures. These are Aminalon, Cerebrolysin + B vitamins.
A properly developed set of rehabilitation measures for children with Down syndrome will allow you to form an adequate personality and lead a familiar lifestyle for the whole family, not to dwell on the diagnosis of Down syndrome.
Down Syndrome. Karyotype and phenotypic characteristics
Complete trisomy of the 21st chromosome is the genetic cause of Down's disease. Cognitive level of newborns with this disease. Hearing, vision, sleep apnea, the state of the cardiovascular system. Immunological aspects and dysfunction of the thyroid gland.
Send your good work in the knowledge base is simple. Use the form below
Students, graduate students, young scientists who use the knowledge base in their studies and work will be very grateful to you.
Hosted at http://www.allbest.ru
Down syndrome is one of the most common genetic pathologies, occurring in approximately one in 700-1000 newborns. The cause of Down syndrome - the appearance of an extra chromosome of the 21st pair - was identified in 1959, almost 100 years after its first description. As you know, the human chromosome set is a constant species trait and consists of 46 chromosomes or 23 pairs, since all human chromosomes are paired. Sex cells (egg and sperm) contain 23 chromosomes, that is, only one chromosome from each pair. Such cells arise during a special mechanism of division - meiosis. During fertilization (the connection of maternal and paternal germ cells), the normal human chromosome set (46 chromosomes) is restored, and an organism develops from the fertilized cell, all cells of which will have 46 chromosomes each. However, sometimes in the process of formation of germ cells of a man or woman, a violation of the mechanism of divergence of paired chromosomes occurs, and both copies of one pair fall into one cell. As a result, the first germ cell will contain one more chromosome (47). In Down syndrome, such an “extra” chromosome is the chromosome of the 21st pair, which leads to the so-called regular trisomy-21 (the presence of three chromosomes of the 21st pair).
The vast majority of cases (95%) of Down syndrome have just such a mechanism of occurrence. However, in 3-4% of cases, the extra 21st chromosome, or even only part of it, is attached to another chromosome in the cells of the parents, resulting in a translocation variant of Down syndrome. This is the only form of the syndrome that can be "inherited" from the parents. The fact is that, although this rearrangement of chromosomes is balanced in the parent (there is no excess or lack of hereditary material) and therefore does not affect his health in any way. When such a cell is combined with a normal cell, a cell with excess chromosomal material arises. In 1-2% of cases, Down syndrome is the result of a violation of cell division after fertilization. Therefore, some of the fetal cells have a normal chromosome set, and some have an extra 21st chromosome. This form of Down syndrome is called mosaic. Thus there are three various options Down syndrome. But regardless of the type of chromosomal defect, Down syndrome is manifested by a characteristic clinical picture, and its specific form can only be determined using a cytogenetic analysis of the chromosome set.
1. genetic cause Down syndrome and its phenotypic features
The genetic cause of Down syndrome was established by Jerome Lejeune and colleagues, who identified an extra chromosome 21 in nine children with Down syndrome. More often this is the result of a complete trisomy of the 21st chromosome, which arose when the chromosomes did not diverge in gametogenesis. Translocation forms are much less common (in such cases, a chromosomal study of the parents is necessary when planning a subsequent pregnancy), as well as mosaic ones.
Down syndrome is usually suspected in a child at birth or in the neonatal period. In very premature newborns, the diagnosis of the syndrome may be late. If the syndrome is detected antenatally, the decision to prolong the pregnancy is made by the family.
The known phenotypic features of Down syndrome are varied. John Langdon Down described this syndrome as mental retardation in patients with high susceptibility to infections and low life expectancy. The two consistent features of Down syndrome, mental retardation and neonatal hypotension, may coexist with a wide range of other anomalies such as congenital heart, gastrointestinal, endocrine and hematological dysfunctions, growth retardation with craniofacial abnormalities, microcephaly, and psychiatric symptoms. At the same time, the presence of all the described anomalies in each particular child is not at all necessary.
Patients with Down syndrome are characterized by the preservation of physical features characteristic of the early stage of fetal development, including narrow slanting eyes, which give the patient an outward resemblance to people of the Mongoloid race, which gave L. Down a reason to call this disease "Mongolism" in 1866 and suggest an erroneous the theory of racial regression, or evolutionary rollback. In fact, Down syndrome is not associated with racial characteristics and occurs in representatives of all races.
The cognitive level of newborns with Down syndrome can be relatively high (IQ 70 to standard newborn IQ 80); there is a slow pace of development, and not a loss of already acquired skills. The lag in psychomotor development usually increases by half a month with each month of chronological age. Defects in expressive speech and a decrease in intellectual development predominate in the early and middle preschool age, whereas non-verbal, social and play acquired skills remain relatively constant. In addition, with the improvement of medical care, the average life expectancy of people with Down syndrome is increasing, from 25 years from 1983 to 49 years in 1997, and on average increases annually by 1.7 years.
2. Growth and development of children with Down syndrome
Children with Down syndrome have slow growth rates from birth until the completion of the growth period, with the lowest rates during infancy and adolescence. The reason for growth retardation is not clear. On average, the height of women is 145 cm, and that of men is 157 cm. It is noted that children with Down syndrome brought up in families are taller than their peers who are in specialized institutions. By the age of one, these children show an increase in average weight for height, and overweight is a significant problem in adults with Down syndrome.
One of the main causes of early death in children with Down syndrome are congenital heart defects, the frequency of which, according to the literature, reaches 50%.
Among the heart defects, the most common are perimembranous ventricular septal defect, persistent ductus arteriosus, atrial septal defect, common open atrioventricular canal (AVC), tetralogy of Fallot and other defects, accounting for less than 1%.
A special role is played by the early diagnosis of congenital heart defects, while it is mandatory to conduct an ultrasonographic examination and timely (before the development of severe circulatory failure) prescription conservative treatment or surgical correction.
In adults with Down's syndrome, in the absence of a history of heart disease, acquired diseases may occur, including mitral valve prolapse with an increase in its insufficiency. It is also necessary to prevent bacterial endocarditis in patients with mitral regurgitation and especially those who have undergone surgery.
Hearing, vision, sleep apnea.
More than half of adults with Down syndrome have conductive or sensorineural hearing loss. People with undiagnosed hearing loss experience increased learning and interaction difficulties. For the timely detection of hearing problems, an audiometric study should be carried out at least once every two years.
Sleep apnea (obstructive) occurs in almost half of people with Down syndrome and is not always diagnosed by doctors. Snoring during sleep, drowsiness, sleeping in unusual positions (on the stomach with bent knees) can be signs of sleep apnea. In this case, an otolaryngological examination and a sleep study cannot be dispensed with to prevent complications such as pulmonary hypertension and cor pulmonale.
An ophthalmological examination is indicated for all children annually, and for adults with Down syndrome - once every two years.
People with Down syndrome often have a deficiency in both cellular and humoral immunity. Patients with frequent intercurrent diseases should be consulted by an immunologist. Deficiency of cellular immunity plays an important role in the development of gingivitis, periodontitis with loss of teeth.
Thyroid dysfunction.
Hypothyroidism, including congenital, occurs in approximately 10-40% of people with Down syndrome. Neonatal screening is very important given the fact that clinical examination may not be sufficient, given the difficulty in diagnosing hypothyroidism in children with Down syndrome due in part to overlapping features. In adults with Down's syndrome, hypothyroidism may masquerade as other diseases, so annual monitoring of thyroid hormone levels is warranted. Treatment of subclinical hypothyroidism (increased levels of thyroid-stimulating hormone (TSH) with normal T4 values) is controversial. The interrelation of subclinical hypothyroidism with hypozincemia and normalization of TSH indices in case of replenishment of zinc deficiency are described. The increased frequency of acquired thyroid diseases occurs at the age of 30-50 years.
Weakness of the ligamentous apparatus.
It is known that people with Down syndrome have weak ligamentous apparatus, which can lead to such disorders as flat feet, scoliosis and instability of the knee joints. Signs of atlantoaxial instability occur in about 13% of adults with Down syndrome, with clinical symptoms in less than 1.5% (in these cases surgery is required). Although the observation of patients with asymptomatic atlantoaxial instability is controversial, caution and possibly withdrawal from sports that involve neck flexion (eg, diving) are generally recommended. X-ray screening for atlantoaxial instability is indicated for all those wishing to compete in the Special Olympics.
Women with Down syndrome can have children. The risk of having a child with Down syndrome is 50%, but the risk of developing other congenital anomalies in children from women with Down syndrome is much higher.
Men with Down syndrome are infertile. Almost half of them have hypogonadism and cryptorchidism, and an increased risk of developing testicular germline tumors is known.
The combination of Down's syndrome and Alzheimer's disease is a difficult task for the doctor, both in diagnostic and therapeutic terms. The clinical picture of Alzheimer's disease in people with Down's syndrome is quite complex, given the premorbid cognitive decline and atypical symptoms.
According to research, average age manifestation of Alzheimer's disease in adults with Down syndrome is 54.2 ± 6.1 years. According to the prevalence of Alzheimer's disease among people with Down syndrome, various data are given in the literature - from 6 to 75%.
To study this problem, a large number of scientific studies are needed, especially on the treatment of Alzheimer's disease in people with Down syndrome.
Anti-inflammatory therapy, estrogens and secretase inhibitors (which may prevent deposition of β-amyloid and thus stop the development of Alzheimer's disease) are being studied. The possibilities of using vitamins C and E are being studied.
Research is already underway on the prophylactic use of acetylcholinesterase inhibitors in Down's syndrome and Alzheimer's disease, but this method needs to be further evaluated.
trisomy down genetic cognitive
As foreign experience shows, the improvement of medical care for children and adults with Down syndrome has significantly improved the quality and length of their lives. careful approach, timely help, and most importantly, the prevention of comorbidities will allow children and adults with this syndrome to maximize their potential.
Bibliography
1. Journal “Down Syndrome. XXI century” edited by N.A. Uryadnitskaya, edition No. 1, 2008.
2. “Changes and continuity in the social competence of children with autism, Down syndrome, and developmental delays. Monograph of the Society for Research in the Field of Child Development, authors: M. Sigman and E. Raskin, 1999.
Hosted on Allbest.ru
Similar Documents
The history of the concept of "Down's syndrome". Causes of the disease, its forms, external signs, its treatment and consequences. The essence of pre-implantation genetic diagnosis, Doppler, three-dimensional ultrasonography and other methods. Tips for pregnant women.
presentation, added 03/22/2010
Frequency of birth of children with Down syndrome. Down syndrome as one of the forms of oligophrenia caused by an anomaly of the chromosome set. Symptoms and clinic of the disorder. Down syndrome research. Neuropsychological data, violations in the work of analyzers.
presentation, added 05/18/2010
Essence, occurrence and methods of studying chromosomal diseases. The main signs of Down syndrome. Edwards syndrome, trisomy 18. Signs of Patau syndrome - trisomy on chromosome 13. Diseases associated with a violation of the number of sex chromosomes.
presentation, added 01/03/2013
Development of children with Down syndrome. Detection of Down syndrome in the fetus using powerful ultrasound equipment. Symptoms of Down syndrome, lag in psychomotor and intellectual development. Recommendations to parents of children with Down syndrome, work with them.
presentation, added 04/24/2010
The concept and main causes of Down syndrome in a child, its general characteristics and clinical signs, diagnostic methods. Features of mental and physical development child with this diagnosis. Degrees of mental retardation.
abstract, added 04.12.2010
A congenital developmental disorder that manifests as mental retardation, impaired bone growth, and other physical anomalies. Possible reasons Down syndrome. Genetic research. What is the difference between a baby with Down syndrome and other children.
abstract, added 01/10/2009
Syndrome as a set of signs or characteristics. Forms of Down syndrome. The spread of pathology, the causes of its occurrence. The effect of maternal age on the likelihood of Down syndrome in a child. Examination for the detection of fetal developmental disorders.
presentation, added 04/20/2012
General characteristics and development factors of chromosomal pathologies: Patau, Down, Edwards, Shershevsky-Turner, Klinefelter syndromes, "cat's cry", double-Y and trisomy X. Their clinical signs and prevalence, directions of research.
presentation, added 04/27/2016
Clinical signs of hydrocephalus. Causes and symptoms of hemophilia A. Description of Down's syndrome (trisomy 21). Aarsky syndrome, or face-finger-genital syndrome. Progeria as a rare genetic disease that accelerates the aging process by 8-10 times.
presentation, added 04/01/2015
Syndromes, the development of which is due to changes in the number or structure of chromosomes. The frequency of chromosomal diseases among newborns. Down syndrome, Patau syndrome, Edwards syndrome. Anomalies of the combination of sex chromosomes. Syndromes of partial monosomy.
presentation, added on 01/06/2013
otherreferats.allbest.ru
Down syndrome
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 electron microscopes were not available to him to find the real cause of the anomaly.
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 sought 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. Over the past 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 the number of registered cases of the birth of children with Down syndrome increases annually.
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%
chest deformity, 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 USA, known to the Russian audience from the films “ Ambulance” and “Mona Lisa Smile”, which 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. This is not the most severe disease in existence, 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. In a pair of 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 more than 50 years. However, due to existing congenital diseases, they develop Alzheimer's disease (senile dementia) much earlier than healthy people, in addition, with age, their health condition is complicated by the development of cardiac diseases and leukemia. 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.
Karyotype - (from karyo. Greek káryon - nut, core and Greek týpos - sample, shape, type) a set of chromosomes, a set of features of chromosomes (number, size, shape) in the cells of the body of an organism of one species or another. The study is carried out during the metaphase of cell division. A common cause of genetic infertility/miscarriage is a change in the number of chromosomes or a change in their structure. Therefore, the study of the karyotype is indicated (in case of infertility) for both spouses. Chromosomes are DNA molecules packaged together with proteins necessary for DNA to function. There are 46 chromosomes in the nucleus of all human somatic cells. Of the 46 chromosomes, 44 or 22 pairs are autosomal chromosomes, the last pair are sex chromosomes. In women, the sex chromosomes are normally represented by two X chromosomes, in men, by two X and Y chromosomes. In all pairs of chromosomes, both autosomal and sex, one of the chromosomes is received from the father, and the second from the mother. In germ cells - in the sperm and in the egg contains 23 chromosomes (haploid set). Spermatozoa are divided into two types depending on whether they contain the X or Y chromosome. Eggs normally contain only the X chromosome. About 99% of the entire cell DNA is concentrated in chromosomes, the rest of the DNA is located in other cell organelles (for example, in mitochondria). DNA in eukaryotic chromosomes is in complex with the main proteins - histones and non-histone proteins, which provide complex packaging of DNA in chromosomes and regulate its ability to synthesize ribonucleic acids(RNA). Every year, a large number of descriptions of new genetically determined anomalies appear in the literature. According to one of the data, more than 2000 hereditary syndromes are known in humans. According to statistics, about 0.7% of children are born with multiple malformations. Karyotype disorders are often accompanied by malformations that are incompatible with life, which ends with intrauterine fetal death and abortion. However, some defects in the karyotype allow the fetus to be born and the child is born with the inherent phenotypic and genotypic features for a particular disease or syndrome. The main anomalies of the karyotype include: Down syndrome, Shereshevsky-Turner syndrome, Edwards syndrome, Klinefelter syndrome. Chromosomal abnormalities are detected in at least 10% of fertilized eggs and in 5-6% of fetuses. Spontaneous abortion with chromosomal defects is usually recorded at the 8-11th week of pregnancy (later spontaneous abortions and stillbirths are possible). According to the results of examinations of 65,000 newborns conducted in different laboratories, significant chromosomal aberrations or changes in the number of chromosomes are detected in approximately 0.5% of children. At least 1 in 700 children has trisomy 21, 18, or 13; about 1 in 350 newborn boys has a 47,XXY or 47,XYY karyotype; one child for every several thousand newborns has a monosomy on the X chromosome; one in 500 has chromosomal aberrations, most of which are genetically compensated. When examining adults, inherited compensated chromosomal aberrations are occasionally detected, as well as a number of people with 47,XXY , 47,XYY and 47,XXX karyotypes. With mental retardation, chromosomal abnormalities are found in 10-15% of patients, and even more often with concomitant anatomical defects. Males with infertility or behavioral problems often have an extra X or Y chromosome. Women with infertility and low fertility often have X chromosome aberrations or X chromosome monosomy. In primary amenorrhea, X chromosome aberrations are found in about a quarter of women. Chromosomal aberrations are often found in infertility in both men and women. Trisomy is the most common chromosomal mutation. Trisomy is the appearance of an extra chromosome in the karyotype. The best-known examples are Down's disease, which is also called trisomy 21. Trisomy 13 is Patau syndrome and trisomy 18 is Edwards syndrome. These trisomies are autosomal. Other autosomal trisomics are not viable, they die in utero. Individuals with extra sex chromosomes are viable. Trisomy for sex chromosomes can be of three types - 47,XXY; 47,XXX; 47,XYY (trisomy 47,XXY, known as Klinefelter syndrome). Clinical manifestations of additional X or Y chromosomes may be minor. Trisomy 47,XXY and 47,XYY occur at a frequency of 1:1000 in women and men, respectively, present with relatively small phenotypic manifestations, and are usually found as incidental findings. Down syndrome (synonyms: trisomy on the 21st chromosome, G 1 -trisomy). Described by Down JLH in 1866. One of the most common congenital human diseases (1 in 660 newborns according to Penrose L.S., Smith G.F. 1966). Distinctive features are mental retardation, muscular hypotonia, a flat face, a Mongoloid slit in the eyes, and small auricles. The probability of nondisjunction of chromosomes in female germ cells increases with the age of the mother. The frequency of birth of a sick child in women aged 15-29 is 1 in 1500 births, 30-34 years - 1 in 800, 35-39 years 1 in 270, 40-44 years 1 in 100, after 45 years 1 in 50. Down syndrome is caused by trisomy of all or most of chromosome 21. Based on the generalized research data, the relative frequency of chromosomal aberrations for this syndrome is as follows: 1. Complete trisomy on the 21st chromosome - 94%; 2. Mosaicism, combining trisomy with a normal set of chromosomes - 2.4%; 3. Translocation of the 21st chromosome or most of it to the chromosomes of group D or G (with approximately the same frequency) - 3.3%. Mosaicism causes less severe manifestations, mental development is delayed, and may not be disturbed, which cannot be predicted by appearance. Mosaicism - the existence in the body of two or more genetically different types cells. Well-developed children with Down's syndrome appearance are more likely to have mosaicism, which is sometimes not easy to confirm. The average IQ of affected adolescents and adults is (according to some estimates) 24. According to statistics, in 1983, patients with Down syndrome lived on average to 25 years, and in 1997 to 49 years. The main cause of early death include congenital heart defects, as well as respiratory diseases, leukemia. There is a weakening of humoral and cellular immunity. Of the comorbidities, rhinitis, conjunctivitis, and periodontitis, which are difficult to treat, are the most common. Edwards syndrome (synonyms: trisomy on the 18th chromosome, E 1 - trisomy). First described by Edwards JH in 1960. The second most common syndrome of multiple malformations. It occurs with a frequency of 1 in 3000 newborns (sick girls are born 3 times more than boys). More than 130 symptoms of this chromosomal abnormality have been described. Distinctive features - clenched fists with overlapping fingers, short sternum, skin pattern in the form of arches on most fingers. Edwards syndrome is caused by trisomy of the 18th chromosome or a large part of it. Most patients have complete trisomy, due to misalignment of chromosomes during meiosis. The likelihood of this discrepancy increases with the age of the mother. The mosaic form of trisomy on the 18th chromosome is easier than complete trisomy. The phenotype ranges from nearly normal to advanced disease. The partial form manifests itself in different ways - depending on which part of the chromosome is doubled. Trisomy on the short arm is accompanied by a blurred clinical picture with normal mental development or mild mental retardation. Children with this syndrome are born weak, half of the children die in the first week of life, few survive to a year. average life expectancy is 14.5 days; children who survive a year (5-10%) suffer from severe mental retardation. Isolated cases of survival of children over 10 years old are known. Patau syndrome (synonyms: trisomy on the 13th chromosome, D 1 - trisomy). First described by Patau K in 1960. It occurs with a frequency of 1 in 5000 newborns. Distinctive features - malformations of the eyes, nose and upper lip, prosencephalic malformations, polydactyly, long protruding nails, focal aplasia of the scalp. The syndrome is caused by trisomy on the 13th chromosome or on its large part. The mosaic form of trisomy is usually milder with varying severity of symptoms and degree of mental retardation. Life expectancy is higher. Trisomy along the short arm and the proximal part of the long arm of the 13th chromosome is manifested by nonspecific signs and usually severe mental retardation. Trisomy in the distal part of the chromosome is manifested by severe mental retardation and death in the early neonatal period. Half of babies die in the first week after birth and only one in ten survives one year. Turner syndrome (synonyms: sexogenic dwarfism, XO syndrome, X-chromosome monosomy syndrome, Ullrich syndrome, Shereshevsky-Turner syndrome). Described in detail by Turner HH in 1938. First seen by Rossle RI in 1922. It occurs with a frequency of 1 in 2500 newborn girls. Distinctive features are short stature, broad chest, nipple hypertelorism, congenital lymphatic edema of the hands and feet. The cause of the syndrome is the nondisjunction of chromosomes during meiosis with the formation of the 45,XO karyotype. One of the two X chromosomes is completely or partially missing. More often than not, the paternal chromosome is missing. The most common manifestations of the disease are short stature and gonadal dysgenesis (underdevelopment or complete absence follicles, ovarian atrophy). Since dysgenesis does not manifest itself until puberty, then in girls with growth retardation in the absence of symptoms that rule out Turner syndrome, a cytogenetic examination may be recommended. The mosaic form of the disease - karyotype 46,XX / 45,XO or 46,XY / 45X and incomplete monosomy on the X chromosome (isochromosome X or deletion of part of the X chromosome) often occurs in a mild form. It is advisable to carry out a cytogenetic study for all girls who, by the age of 13, have no thelarche and adrenarche, and also have primary or secondary amenorrhea with an elevated FSH content. It has been shown that during fetal development, the ovaries develop normally, however, primordial follicles, apparently, are not formed and the ovaries subsequently atrophy. Growth retardation in girls is sometimes noticeable at birth. Before 30 years the child grows normally, but with a delay in the maturation of bone tissue, and from 3 to 12 years, on the contrary, bone matures normally, but growth is retarded. After 12 years, the growth and maturation of bones is slowed down, a tendency to be overweight appears. Growth without treatment is (on average) 143 cm. Due to the developing ovarian atrophy, such women are infertile. Adults with Turner syndrome have an increased incidence of aortic dissection. Increased incidence of arterial hypertension, diabetes mellitus, arterial hypertension, stroke. 6% of girls have a mosaic karyotype - 45.XO/46.XY and they have a significantly increased risk of gonadoblastoma. Klinefelter syndrome (synonyms: XXY syndrome, syndrome 47, XXY, Klinefelter-Reifenstein-Albright syndrome). Described by Klinefelter HF in 1942. It occurs with a frequency of 1 in 500 newborn boys. Distinctive features: hypogonadism, long legs, decreased intelligence, behavioral disorders. The manifestation of the syndrome is associated with the presence of an additional X chromosome in the male karyotype. The reason, in about half of the cases, is the nondisjunction of chromosomes in the 1st division of meiosis during spermatogenesis, the other half is a violation of oogenesis, and in a small number of cases, a violation of mitosis in fertilized cells. The older a man becomes, the more often spermatozoa with both sex chromosomes are found in him, i.e. the risk of having a child with Klinefelter's syndrome should be higher. The syndrome is the most common cause male hypogonadism and infertility. From childhood, such patients are characterized by a eunuchoid physique - tall, disproportionately long limbs, long legs. Speech development late, mental infantilism, uncertainty, or vice versa, self-confidence, impaired judgment are manifested. The penis and testicles are relatively small since childhood, testosterone synthesis, with rare exceptions, is reduced by half. Secondary signs are poorly developed, a third of adolescents have gynecomastia. Rare symptoms in Klinefelter's syndrome include: cryptorchidism, scoliosis, diabetes mellitus, chronic bronchitis, mild ataxia, trophic ulcers of the legs, varicose veins, deep vein thrombosis, osteoporosis, breast cancer (20 times more often), extragonadal tumors (more often in age 15-30 years), autoimmune diseases. In childhood, symptoms are minimal, the clinical picture develops during puberty and post-puberty and reflects the degree of androgen deficiency. With a mosaic form of the syndrome (46,XY / 47,XXY), the disease proceeds more easily with less testicular disorders. A variant of Klinefelter's syndrome - XXYY syndrome is characterized by more severe mental retardation and severe behavioral disorders. XXX and XXXX syndromes (synonyms: X-chromosome polysomy, XXX syndrome - triplo-X syndrome, X-chromosome trisomy syndrome, XXXX syndrome - X-chromosome tetrasomy syndrome, tetra-X syndrome). XXX syndrome is described by Jacobs PA et al. in 1959. The 47,XXX karyotype occurs with a frequency of 1 per 1000 newborn girls. The manifestation of the syndrome is associated with the presence of an additional X chromosome (one or two) in the female karyotype. The cause of XXX syndrome is mainly the nondisjunction of chromosomes during the 1st division of meiosis. In such patients, motor speech is often impaired, auditory memory is weakened, the acquisition of motor skills occurs with a delay, poor coordination of movements and clumsiness are typical. IQ is reduced (80 -90). A third of adolescents have behavioral disorders - isolation, antisocial behavior, mild depression. Over time, these disturbances disappear. Puberty is normal. XXXX syndrome is described by Carr DH et al. in 1961. For this syndrome clinical manifestations characterized by mental retardation. Growth is normal or high. Facial features resemble Down syndrome. IQ is reduced (average 55). Characteristic is the delay in the development of speech and behavior. These patients often have disorders menstrual cycle and reduced fertility, but their children are usually healthy. XXXXXX syndrome (synonyms: X-chromosome pentasomy syndrome, penta-X syndrome). XXXXX syndrome was described by Kesaree N and Wooley PV in 1963. Distinctive features: Mongoloid incision of the eyes, open arterial incision of the eyes, small palms, clinodictalia of the fifth finger. The syndrome is due to the presence of three additional X chromosomes in the karyotype of women. The extra chromosomes come from the mother. This syndrome of clinical manifestations is characterized by mental retardation, growth retardation, short stature, microcephaly, slightly Mongoloid eye shape, sunken nose bridge, short neck, low hairline, malocclusion, congenital heart defects - open mitral defect, ventricular septal defect. IQ in the range of 20-75. Cat's eye syndrome (synonyms: iris colomba syndrome and anal atresia, Schmid-Fraccaro syndrome). Distinctive features: iris colomba, anti-Mongoloid eye slit, anus atresia. In such patients, an extra chromosome is found, consisting of two identical sections of the 22nd chromosome, containing the entire short arm along with satellites, the centromere and the short part of the long arm. Those. this area is present in 4 copies. Sometimes the disease is due to a duplication of the 22q11 segment. Colomba of the iris and atresia of the anus, as the main symptoms of the disease, are present simultaneously only in 9% of cases. The disease is characterized by: mild mental retardation, sometimes delayed emotional development with normal intelligence, slight hypertelorism of the eyes, lower iris or retinal colomba, antimongoloid incision of the eyes, anterior fossae, ear appendages, congenital heart defects in more than a third of patients (complete anomalous confluence of pulmonary veins , defects of the interatrial and interventricular septum), atresia of the anus in combination with rectal fistulas, hypospadias, hydronephrosis, renal agenesis, vesicoureteral reflux. Rare symptoms include: microcephaly, hearing loss, stenosis of the external auditory canal, bile duct atresia, cleft palate, polycystic kidney disease, Meckel's diverticulum and others. Trisomy syndrome on the 8th chromosome. The first works describing the syndrome date back to 1963. The syndrome is caused by trisomy on the 8th chromosome, as a rule, it is a mosaic trisomy, complete trisomy, apparently, is rarely compatible with life. Clinical manifestations of this syndrome are: mental retardation varying degrees heaviness, long narrow torso, low to high growth, anomalies of the scapula and sternum, short neck, narrow pelvis, hip dysplasia, malformations of the heart, kidneys, ureters, poor coordination of movements, bulging forehead, deep-set eyes, wide bridge of the nose, wide nostrils, puffy lips, everted lower lip, lower micrognathia, narrow high palate/cleft palate, large cupped ears with thick curl, camptodactyly of 2-5 fingers and toes, incomplete supination at the elbow joint, deep palmar and plantar sulci, large joint contractures , abnormal nails. Rare symptoms include: aplasia of the patella, bifurcated hair, conductive hearing loss, abnormal structure of the vertebrae (split vertebrae, accessory lumbar vertebrae), scoliosis, cryptorchidism, doubling of the jejunum, agenesis of the corpus callosum, germ cell tumors, gastric leiomyosarcoma. The prognosis of the disease is determined by the severity of mental retardation.