Please refer to:

1. Common karyotypes are:

47, XX, +2 1 simple trisomy, female

47, XY, +2 1 simple trisomy, male

46, xx (xy)/47, xx (xy), +2 1, chimera

46，XX(XY)，-2 1，+t(2 1； 2 1) robertsonian translocation.

The meiosis of simple trisomy should be disordered.

Five, genetic analysis of congenital idiot:

The typical 2 1 trisomy is almost new and has nothing to do with the karyotype of parents. It is the result of not separating during meiosis. Non-segregation can occur in the first meiosis or the second meiosis. In men, meiosis is going on all their lives, and sperm is constantly produced by spermatogonia through spermatogenesis, or "fresh". In women, all eggs have passed the first meiosis at birth, and they are in the resting stage or nuclear reticular stage until ovulation. Therefore, oocytes are affected by internal and external environmental factors for a long time and are constantly aging. All these may lead to the occurrence of non-separation, and may also explain why older mothers are prone to give birth to children with congenital stupidity.

Only a small part of the typical 2 1 trisomy is hereditary, that is, because the mother is a trisomy patient. In addition, it cannot be ruled out that some mothers with normal phenotype are actually chimeras, but the proportion of abnormal cells is very small, such as only existing in certain tissues or ovaries. Trisomy cells in the ovary may lead to the birth of trisomy children. The possible indirect evidence of this situation is that 10% of the children's mothers have abnormal dermatoglyphics. Therefore, although their other phenotypes are normal, they may be potential chimeras, and their children may get extra chromosomes. It can be seen that it is quite difficult to confirm or deny chimera. If the patient is male and infertile, there is no problem of passing it on to the next generation.

Patients with chimeric three body 2 1 have two or more cell lines, which is the result of mitosis after zygote. If the first cleavage does not occur, two cell lines will be produced, 47, +2 1 and 45, -2 1. The latter cells are difficult to survive. Therefore, most mosaics will not separate during mitosis, and all mosaics have normal cell lines. The ratio of the two cell lines is not the same in each tissue, and the percentage of abnormal cells is usually higher in fibroblasts than in blood cells. According to the literature, no trisomy cells were found in patients' blood cells, but 65438 07% fibroblasts were trisomy cells, which indicated that trisomy cells were subjected to different selection pressures in various tissues. Chimera may also be the result that the abnormal zygote of 2 1 trisomy is not separated, that is, one cell line loses a number 2 1 and returns to normal, while the other cell line is still 2 1 trisomy.

There are unbalanced translocation chromosomes in the cells of patients with translocation type 2 1. The latter is usually formed by the centromere fusion (Luo translocation) of a group of D or G chromosomes and the long arm of 2 1 chromosome. 55% of q2 1q translocation is new, and 45% is due to the balanced translocation of one parent. The translocation of 2 1qGq is almost completely new (96%), and only 4% is hereditary. The genetic consequences of various translocations are different. Dq2 1q balanced translocation carriers can form six gametes through meiosis, and after fertilization, they can produce three kinds of fetuses: normal fetuses, trisomy and children of balanced translocation carriers, except those who cannot develop. Therefore, it is of great significance to detect the parents of balanced translocation carriers. In fact, apart from the mother's age, little is known about the etiology of typical 2 1 trisomy, and effective prevention is limited to prenatal diagnosis after pregnancy. In recent years, it has been found that mothers who gave birth to triplets 2 1 have increased serum alpha-fetoprotein during pregnancy, which seems to be a screening and prevention method. For the translocation of 2 1 trisomy, parents can be examined before pregnancy or before marriage and given guidance.

2 1qGq translocation is mostly new. The genetic meanings of 2 1q22q and 2 1q2 1q are not exactly the same. If one parent is the carrier of 2 1q2 1q, it is impossible to give birth to a fetus with normal phenotype, because they can only give birth to a trisomy or a haploid zygote. The genetic consequences of 2 1q2 1q translocation are similar to those of Dq22q, except that the former is mostly transmitted by the father and the latter by the mother.

Sixth, genetic counseling for congenital idiots.

It is of great practical significance to estimate the recurrence risk of 2 1 trisomy. 2 1 The risk of recurrence is different for all types of trisomy. For a typical 2 1 trisomy, having one child does not increase the risk of having another child, at least in theory. Therefore, if both parents' karyotypes have been checked to be normal, there is no reason to persuade them not to give birth, or to excessively aggravate the existing doubts. However, there are indeed reports that some families have more than two patients with typical three symptoms. Some parents (usually mothers) have been proved to be chimeras, although the proportion of trisomy cells is not high; Others have found translocation of other chromosomes. However, most families cannot find a reasonable explanation. Therefore, some assumptions are put forward. For example, germ cells are chimeric and familial, but these assumptions need to be confirmed. Therefore, it is difficult to estimate the recurrence risk of typical 2 1 trisomy, and the risk rate proposed by each author is not the same. Some authors assume that if a mother has given birth to a triplet before the age of 30, the risk of recurrence is 1-2%, but the risk rate after the age of 30 will not increase compared with the same age group. In short, for parents who have given birth to typical trisomy children, what counselors can do is to exclude them as chimeras as much as possible through chromosome examination.

About 1/2 cases were newly added, and another 1/2 cases were caused by balanced translocation of one parent. The possibility of recurrence of the former is very small, and the risk of recurrence caused by balanced translocation can be estimated according to real experience. If the Dq2 1 translocation carrier is a mother, the risk of giving birth to a child with translocation is 10- 15% (some authors think it is 16%), and if it is a father, the risk is less than 5%. The situation of 2 1q22q translocation is basically the same, but the percentage of translocation chromosomes is more than that of D/g translocation, and some data show that the risk rate is below 10%. The offspring of carriers of 1Q2 1Q balanced translocation are all triplets. Carriers are not suitable for childbearing.

2. Down syndrome (2 1 trisomy syndrome; Congenital stupidity often leads to many other typical characteristics of children, such as mental retardation, characteristic face, microcephaly and short stature.

The incidence of Down's syndrome in live births is about 1/800, but there is significant variation in the incidence among pregnant mothers of different ages: pregnant mothers are less than 20 years old, and the incidence is1/2000; When the pregnant mother is over 40 years old, the incidence rate rises to about 1/40 (Table 247- 1). About 20% babies with 2 1 trisomy syndrome are born to mothers over 35 years old. 2 1 trisomy syndrome can be caused by karyotype 2 1 trisomy, translocation and chimerism.

About 95% cases of 2 1 trisomy have complete extra chromosomes, 95% of which are from mothers.

Translocation Some 2 1 trisomy syndromes show 46 chromosomes, but in fact there are 47 chromosomes in genetic material, and the extra 2 1 chromosome is translocated or attached to another chromosome.

t( 14； 2 1) is the most common translocation type, in which the redundant chromosome 2 1 is attached to chromosome 14. About half of the cases have normal karyotypes, indicating that the child has neonatal translocation. In the other half, one of the parents (almost always the mother) has 46 chromosomes, but one of them is t (14; 2 1)。 Theoretically, the probability of the carrier's mother giving birth to a child with 2 1 trisomy syndrome is 1:3, but due to unknown factors, the actual risk rate is low (about 1: 10). If the father is a carrier, the risk rate of actually giving birth to a child with 2 1 trisomy syndrome is 1:20.

t(2 1； 22) As the second common translocation, the probability that a mother carrier gives birth to a child with 2 1 trisomy syndrome is 1: 10, and the risk rate of a father carrier is lower. In rare cases, both parents are T (21; 22) carriers, 100% surviving offspring are all patients with 2 1 trisomy syndrome.

Chimera is called chimera when two different cell types exist in the same individual. The chimera of 2 1 trisomy syndrome is presumed to be caused by chromosome segregation in embryonic stage. Most cases have two cell lines, one with normal chromosomes and the other with 47 chromosomes. The relative proportion of cell lines can be different between different individuals or in different tissues and organs of the same individual. The intelligence of patients is related to the proportion of trisomy cells in the brain. A few individuals with chimeric three body 2 1 syndrome have normal intelligence and almost no symptoms in clinic. In 2 1 trisomy syndrome, the incidence of chimera is unknown. If parents' germ cells have 2 1 trisomy chimera, the chances of having a second child will be greatly increased.

Symptoms and signs

Newborns are quiet, crying less, muscle tone is low, and neck skin is usually thickened. Ultrasound examination can be diagnosed as cervical edema. Physical and intellectual development is backward, with an average IQ of about 50.

Special signs include microcephaly, flat head pillow and short stature. The outer canthus of the eye is inclined upward, the inner canthus is covered with skin, the nose is flat, the tongue is big, and it often sticks out of the mouth. Ears are small and round, hands are short and wide, and there is often a single palmar fold line (ape fold), fingers are short, the fifth finger is bent, and there are often only two phalanges. There is often a wide groove between the first toe and the second toe of the foot, and there are characteristic dermatoglyphics on both hands and feet.

In patients with 2 1 trisomy syndrome, the incidence of neonatal congenital heart disease is about 40%, which often involves ventricular septum or forms abnormal atrioventricular channel. In addition, the incidence of almost all congenital anomalies in patients increased, especially duodenal atresia.

Many patients can develop thyroid diseases, which are difficult to find without endocrine examination. Patients are prone to audio-visual impairment and should be screened routinely.

Anatomically, the brain tissues of all adult patients with 2 1 trisomy present typical microscopic manifestations of Alzheimer's disease, and most of them are accompanied by corresponding clinical symptoms. Some adult female patients have fertility, and the possibility of their fetuses suffering from Down syndrome is 50%, and most of them suffer from spontaneous abortion. Male patients with 2 1 trisomy syndrome are infertile.

prognosis

Because of the high incidence of patients complicated with heart disease and acute leukemia, life expectancy tends to be reduced. Many patients can live to adulthood, but they age quickly and often die around 40 or 50 years old.

There are 46 chromosomes in human cells. When the sex cells or fertilized eggs of husband and wife divide before and after conception, due to various reasons (aging, radiation exposure, environmental pollution and virus infection, etc. ), chromosome division is not just right, resulting in 47 chromosomes in the fetus. Generally, chromosome 2 1 changes from two to three. If this kind of cell changes, the whole situation of human body will also change, which is the so-called congenital stupidity, 2 1 trisomy syndrome and congenital dementia. This disease was first proposed by Down's in 1866, so it is also called D.S. (Down's syndrome, abbreviated as D.S.

However, there are a few children (5%-8%) whose chromosomes are not 2 1 trisomy, but the extra 2 1 chromosome is translocated to the D chromosome (usually numbered as 13- 15) or there is a chimera between the normal cell line and the 2 1 trisomy cell line.

Children are generally born very young, and about 20% are premature. Children have a typical face, regardless of race, and their facial features are more like other congenital fools than their own compatriots. Such as: wide eye distance, hanging eyes, the inner corner of the eye covered by wrinkles, low nose bridge, small auricle and small mouth, it is difficult to accommodate the tongue, so the tongue is often spit. The skin is red, the limbs are short, the fingers are short and thick, and the little finger is particularly short and bent inward. The navel is often raised; Often accompanied by duodenal atresia; 50% children have congenital heart malformation. Most children can sit up after 65,438+0 years old and start walking at the age of 3. They are gentle and seldom aggressive, so sometimes they are silly and cute. Their intelligence develops slowly and they don't know how to calculate. Their IQ ranges from 25 to 50, but occasionally some patients are educated. The average IQ of their parents will affect their intellectual development. Children like to imitate and repeat some simple actions, and some can even become band directors.

The average life span of patients with congenital dementia is 16 years old. Due to heart disease and other factors, about 50% patients died before the age of 5, and less than 3% patients lived to be over 50. Male patients are infertile; Female patients have fertility, but about half of their offspring are also congenital fools. Congenital heart malformation in this syndrome is related to the onset and early and late death of most patients.

The birth rate of children with congenital dementia is about 1.3‰, and that of mothers aged 35-39 is 0.4%. 65438+40-44 years old accounted for 0.2%, and over 45 years old accounted for 4%. Because the incidence of congenital dementia tends to increase with the increase of pregnant women's age, it often leads to the wrong idea that only elderly (over 34 years old) pregnant women will give birth to children with congenital dementia. Actually, it's not. According to national statistics, only 20% of children with congenital dementia are born to pregnant women over 34 years old, while the other 80% are born to ordinary young pregnant women. It can be seen that pregnant women may be pregnant with children with congenital dementia as long as they are old or young, but the probability is different. In view of this, in order to avoid the occurrence of congenital dementia in children, all countries in the world are committed to prenatal examination of congenital dementia, and its examination methods include diagnosis and screening. The so-called diagnosis examination is to do amniocentesis at 16-20 weeks of pregnancy. This method can also check whether there are other chromosomal abnormalities besides congenital idiocy. Because of the high cost (about 1300 yuan), the risk rate is about 0.5- 1%, even the elderly pregnant women are mostly unwilling to accept this kind of examination abroad. Therefore, under the consideration of economy and safety, non-invasive maternal serum and urine screening is more convenient, safer and cheaper than amniocentesis. However, since it is defined as screening, we should understand that although this method is convenient to use, it can not screen all congenital stupid fetuses, so all countries in the world put this method on the front line of prenatal screening for congenital stupid fetuses, which gives most young pregnant women who have not had amniocentesis an extra layer of protection.