Down syndrome

Down syndrome is the most commonly diagnosed chromosomal syndrome. It was clinically described by Down in 1866.

Karyotypically identified in 1959. Children with this syndrome have an extra copy (trisomy) of chromosome 21, which leads to the development of mental (reduced intelligence) and physical disorders (various malformations of internal organs).

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Epidemiology

The population frequency does not depend on gender and is 1:700 without taking into account the age of the parents. Due to the spread of screening programs for pregnant women in the first or second trimester, the number of newborns with Down syndrome has begun to decrease.

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Causes Down syndrome

The true causes of this disease have not been deciphered, however, mutagenic factors of the external environment apparently play a certain role in this.

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Risk factors

Main risk factors for Down syndrome.

• Mother's age is over 35 years.
• Regular trisomy of chromosome 21 (47, t21).
• Translocation (exchange of chromosome regions) of chromosomes 14 and 21 (46, tl4/21).
• Chromosome translocation 21/21 (46, t21/21).
• In 2% of cases, a mosaic variant occurs if non-disjunction of these chromosomes occurs at the first stages of zygote division. In this case, the karyotype looks like 47; 21+/46.

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Pathogenesis

The pathogenesis of Down syndrome is not completely clear. Probably, the imbalance of chromosomes in somatic cells leads to disruption of the functioning of the genotype. In particular, it has been established that in trisomy, myelination of nerve fibers and the production of neurotransmitters are affected.

Depending on the changes in chromosome 21, there are three types of Down syndrome:

1. Trisomy 21: About 95% of people with Down syndrome have trisomy 21. In this form of Down syndrome, each cell in the body has 3 separate copies of chromosome 21 instead of the usual 2.
2. Translocation of chromosome 21: This type occurs in 3% of cases of this syndrome. In this case, part of chromosome 21 is attached to the arm of another chromosome (most often, this is chromosome 14).
3. Mosaicism: This type occurs in 2% of cases of the disease. It is characterized by the fact that some of their cells have 3 copies of chromosome 21, and some have the typical two copies of chromosome 21.

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Symptoms Down syndrome

Children with Down syndrome have a flattened face with a Mongoloid eye shape and reduced auricles (<3 cm vertical length in newborns) in combination with generalized muscle hypotonia, clinodactyly of the little fingers with a single flexor fold on the palms and little fingers. Congenital malformations include duodenal atresia, annular pancreas, and ventricular septal defects. Less common are Hirschsprung's disease and congenital hypothyroidism.

Soon after birth, there is a marked delay in psychomotor and physical development. Later, severe mental retardation and short stature develop. Children with Down syndrome have impaired immunity, making them very vulnerable to bacterial infections. They have a 20-fold increased risk of developing acute leukemia. The reasons for this are unclear.

Other diseases that may accompany Down syndrome:

• Hearing loss (in 75% of cases);
• Obstructive sleep apnea syndrome (50 - 75%);
• Ear infections (50 - 70%);
• Eye diseases, including cataracts (up to 60%).

Other, less common diseases:

• Hip dislocation;
• Thyroid disease;
• Anemia and iron deficiency.

Few survive to adulthood. Life expectancy in such patients is limited by malformations of the heart and large vessels, gastrointestinal tract, manifestation of acute leukemia and infection.

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Diagnostics Down syndrome

Diagnosis is not difficult, but in premature newborns (before 34 weeks of gestation) it may be delayed.

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Screening tests

Screening tests are a combination of a blood test that measures the amount of various substances in the mother's serum [eg, MS-AFP, prenatal diagnosis (triple screening, quadruple screening)] and an ultrasound of the fetus.

Since 2010, a new genetic test has been available to diagnose Down syndrome, which involves detecting small pieces of the developing baby's DNA that circulate in the mother's blood. This test is usually performed in the first 3 months of gestation.

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Diagnostic tests

Diagnostic tests are performed after a positive screening test to make a definitive diagnosis:

1. Chorionic villus sampling (CVS).
2. Amniocentesis and cordocentesis.
3. Umbilical cord blood test (PUBS).

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Treatment Down syndrome

Down syndrome has no specific treatment methods. Courses of nootropic and vascular drugs are used. Educational activities are of great importance, as they can significantly adapt these patients socially.

All pregnant women over 45 years of age are recommended to undergo intrauterine karyotyping of the fetus. This is done for the purpose of timely artificial termination of pregnancy in cases of detection of an abnormal karyotype. If a patient is diagnosed with a translocation variant of Down syndrome, the parents must be karyotyped in order to predict the risk of similar pathology in subsequent children.

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Forecast

With regular trisomy of chromosome 21, the risk of having a child with a disease such as Down syndrome is low and is not a contraindication for childbearing. In women over 35 years of age, the likelihood of developing regular trisomy of chromosome 21 increases.

In case of translocation, the risk of having a child with this disease again ranges from 1 to 10% and depends on the type of translocation and the sex of the carrier of this balanced karyotype rearrangement. In case of 21/21 translocation in one of the parents, the risk of having a child again is 100%.

Sometimes not all of the child's cytogenetically examined cells contain the extra chromosome 21. These cases of mosaicism are the most difficult in the process of medical and genetic counseling of parents in terms of predicting the future intellectual development of a child who has Down syndrome.

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