Trisomy 21, also known as congenital dysgenesis or Down syndrome, is the most common chromosomal disorder in newborns, with an incidence of 1 in 700. It was first described by John Langdon Down in 1866, and with the advent of karyotyping techniques, Lejeune et al. confirmed in 1959 that the disorder was caused by an extra chromosome 21.
Trisomy 21 is caused by an extra chromosome 21
The extra chromosome 21 originates from the non-disjunction of chromosome 21 during meiosis in germ cells, of which 90-95% originates from the mother, 3/4 of this non-disjunction occurs in meiosis I, 1/4 in meiosis II, and the other 3%-5 -5% originated from the father, in contrast to the meiotic error that originated from the mother, which occurs 1/4 in meiosis I and 3/4 in meiosis II.
2, translocation type 21 trisomy accounts for 4% of trisomy 21, there is a 21 received in translocation to group D (13, 14, 15) or G (21, 22) chromosomes, so in the record, the total number of chromosomes in this type of patients is 46, with 14, 21 translocation is the most common. Among translocation type 21 trisomy, 3/4 are de novo, i.e. both parents have normal karyotype, while 1/4 are familial or hereditary, and one of their parents is a Robertson translocation carrier involving chromosome 21. The theoretical probability of such couples producing a translocation type 21 trisomy embryo is 1 in 6.
3. Chimeric trisomy 21 accounts for 2-3% of cases and usually originates from the non-separation of chromosome 21 in mitosis, with some cells in the patient being 46N and some being 47N, +21.
Trisomy 21 karyotype
1. standard type, with each of the three chromosome 21s existing independently, with a total of 47 chromosomes.
2. 14/21 translocation type, in which one chromosome 21 is linked to one chromosome 14, with a total of 46 chromosomes.
The relationship between maternal age and trisomy 21 is well established, showing a positive correlation, with a higher incidence of trisomy 21 with higher maternal age, as shown in Table 1. the role played by the age factor is particularly pronounced in pregnant women over 35 years of age, however, only with trisomy 21 of maternal origin, and studies have shown that a reduced rate of recombination between chromosome 21 monomers may result in the non-segregation of chromosome 21 in meiosis, with higher age making This possibility is increased by advanced age. Trisomy 21 of paternal or mitotic origin is not affected by maternal age. To date, there is insufficient evidence to link paternal age to trisomy 21 occurrence.
Recurrent trisomy 21 in families or siblings is very rare and the cause of recurrence may be related to gonadal chimerism. Nielsen et al. 1988 reported a family in which the couple had standard trisomy 21 in 6 of 11 pregnancies and the remaining 5 pregnancies of unknown karyotype ended in neonatal death or spontaneous abortion, and karyotyping showed 46N in maternal peripheral blood and 47 in ovarian tissue, +21 /46N.
[Clinical manifestations].
The clinical manifestations of trisomy 21 often involve multiple systems, with peculiar facial features, mental retardation, hypotonia and through palps being the most prominent.
1.Special facial features include wide eye spacing, upward sloping external eye corners, low nasal bridge, short nose, often open mouth and extended tongue, salivation, and small auricles. The child’s head is short, the occipital region is flat, the third fontanel is visible in newborns, the palatal arch is high, and the neck is thick and short or has a webbed neck in 80% of patients.
2. All trisomy 21 patients show varying degrees of mental retardation, with IQs between 25-60. After the age of 40, almost all patients show neuropathological changes of Alzheimer’s disease, thus exhibiting the clinical features of senile dementia.
3, Hypotonia and growth retardation are characteristic of all children with trisomy 21. 60-85% of patients have through palms, short and thick hands, short fifth fingers, and widely spaced first and second toes.
3. Joint atrioventricular channels are the most common cardiac malformation in this syndrome, accounting for about 40% of cases. Other common malformations include ventricular septal defect, atrial septal defect, and tetralogy of Fallot.
The incidence of leukemia is 10-20 times higher than normal in patients with trisomy 21, and some newborns develop leukemia-like reactions. Other clinical manifestations include immunodeficiency, duodenal atresia, etc. Male patients have small penis, small scrotum, cryptorchidism, and 100% infertility. Female patients usually have no menstruation, but a few can have pregnancy and childbirth and may pass the disease on to their offspring.
Prenatal diagnosis]
Fetal karyotype analysis is still the main method for prenatal diagnosis of trisomy 21. Chorionic villus culture, amniotic fluid culture or umbilical cord blood culture can be chosen according to the gestational age. For some pregnant women of older gestational age who are eager to obtain diagnostic results, fluorescence in situ hybridization technique can also be used for rapid diagnosis of uncultured cells, but FISH cannot present all chromosomal states at once, so it can only be used as an auxiliary method in specific cases.
【Processing principles
Most of the trisomy 21 combined with severe malformations have a poor prognosis, which can be stillbirth, stillbirth or neonatal death. The average life expectancy of surviving children is about 20 years old and they cannot take care of themselves, so once trisomy 21 is clearly diagnosed, all pregnancies should be terminated in time to avoid the birth of affected children as the management principle. In this process, we should also understand the family history, the maternal age and whether there are other trisomy 21 patients in the family is an important basis for determining the risk of recurrence of the next child. The risk of recurrence in the next pregnancy does not increase because of the occurrence of trisomy 21, but is equal to that of pregnant women in the same age group; for couples who have had two or more pregnancies with standard trisomy 21, the chromosomes of both partners should be examined, paying special attention to the presence of chimerism, with or without chimerism, should be informed of the high risk of recurrence in the next pregnancy.
For trisomy 21, in addition to termination of pregnancy, chromosomal examination of both spouses should be performed to clarify whether one of the spouses is a translocation carrier. If one of the couple is a normal chromosome, the risk of recurrence is less than 1%; if one of the couple is a 21 or 21 Robertsonian translocation, the risk of recurrence of trisomy 21 in the next pregnancy is 100% and they should be advised to sterilize; if one of the couple is a 21 and other proximal mitotic chromosome (13, 14, 15, 22) Robertsonian translocation, the risk of recurrence varies greatly depending on whether the male or female partner is the carrier. If the carrier is male, the risk of recurrence is 1%, but if the carrier is female, the risk of recurrence increases to 15%; if one of the couples has a reciprocal translocation of 21 to another chromosome, the risk of recurrence of the translocation type 21 trisomy is 10%.