Down syndrome( trisomy 21) - Causes, symptoms and treatment. MF.

Down syndrome( a pathology, also called trisomy 21) is a genetic disorder that occurs in about 1 in 800 newborns. It is the leading cause of cognitive impairment. Down's syndrome is associated with mild and moderate developmental delay, people with the disease have characteristic features, low muscle tone in early childhood. Many people with Down's syndrome have heart defects, an increased risk of developing leukemia, early onset of Alzheimer's disease, gastrointestinal diseases, and other health problems. Symptoms of Down's syndrome range from mild to severe development.

People with Down's Syndrome

Causes of Down Syndrome

Down syndrome is named after Dr. Langdon Down, who in 1866 first described the syndrome as a disorder. Although the doctor described important and underlying symptoms, he did not correctly determine what exactly caused this pathology. And only in 1959, scientists discovered the genetic origin of Down syndrome. Genes for additional copies of the 21st chromosome are responsible for all characteristics associated with Down syndrome.

As a rule, each human cell contains 23 pairs of different chromosomes. Each chromosome carries genes that are necessary for the proper development and maintenance of our body. In the concept, a person inherits 23 chromosomes from the mother( through the egg) and 23 chromosomes from the father( through the sperm).However, sometimes a person inherits an additional chromosome set from one of the parents. In the case of Down syndrome, two copies of the 21st chromosome from the mother and one 21 chromosomes from the father most often inherit, in total, there are three chromosomes 21. It is because of this type of inheritance that Down syndrome is called trisomy on the 21st chromosome.

About 95% of people with Down syndrome inherit the entire complementary chromosome 21. Approximately 3% to 4% of people with Down syndrome do not inherit the entire complementary chromosome 21, but only some additional genes from the 21st chromosome that are attached to the other chromosomerule, chromosome 14).This is called translocation. Translocations are in most cases random events during conception. In some cases, however, one of the parents is the bearer of a balanced translocation: the parent has exactly two copies of the chromosome 21, but some genes are distributed on another chromosome. If the child inherits the chromosome with the additional genes of the 21st chromosome, the child will have Down syndrome( two chromosomes 21, plus additional genes from the 21st chromosome connected from another chromosome).

About 2% -4% of people with Down's Syndrome inherit additional chromosome 21 genes, but not in every cell of the body. This is mosaic Down syndrome .These people can, for example, inherit a part of the chromosomal abnormalities, that is, an additional 21st chromosome may not be present in all human cells. Since in people with mosaic Down syndrome the number of such cells varies within different limits, they often will not have all the signs of Down's syndrome, there may not be as strong intellectual disorders as people with complete trisomy on 21 chromosomes. Sometimes mosaic Down syndrome is so insignificant that it will remain unnoticed. On the other hand, mosaic Down's syndrome can also be misdiagnosed as trisomy on chromosome 21, if genetic testing has not been done.

There is a question that scientists around the world are working on now, which of the additional genes in the 21st chromosome lead to the development of certain symptoms. There is still no exact answer to this question. Scientists believe that increasing the number of specific genes changes the interaction between them. Some genes become more active than others, while others are less active than usual. As a result of this imbalance, differentiation and development of both the organism itself and the psycho-emotional sphere are violated, including intellectual development. Scientists are trying to find out which genes from the three variants of 21 chromosomes are responsible for this or that sign of Down syndrome. At present, about 400 genes on 21 chromosomes are known, but the majority function remains unclear to this day.

The only known risk factor for Down syndrome is the age of the mother. The older the woman at the time of conception, the greater the risk of having a child with Down syndrome. The age of the mother at conception is Down's syndrome risk:

25 years old 1 of 1250
30 years old 1 of 1000
35 years old 1 of 400
40 years old 1 of 100
45 years old 1 of 30

Down syndrome is not a hereditary disease, although there is a predisposition to its development. In women with Down's syndrome, the probability of conceiving a sick child is 50%, often a spontaneous abortion occurs. Men with Down's Syndrome are infertile, except for the mosaic variant of the syndrome. In carriers of genetic chromosome translocation, the likelihood of a child with Down's syndrome will also be increased. If the carrier is a mother, a child with Down's syndrome is born at 10-30%, if the father's carrier is 5%.

Healthy parents who have a child with Down's syndrome have a 1% risk of conceiving another child with Down's syndrome.

Symptoms and signs of Down syndrome manifestation.

Despite the severity of Down's syndrome in the range of mild to severe, most people have well-known external manifestations. They include the following features:

• Flat face and nose, short neck, small mouth sometimes with a large, sticky tongue, small ears, slanting eyes that can have small skin folds at the inner corner;
• White spots( also known as Brushfield spots) can be present on the colored part of the eye;
• The arms are short and wide, with short fingers, and with one fold on the palm;
• Weak muscle tone, development and growth retardation.
• Arched sky, tooth anomalies, flat bridge of nose, furrowed tongue;
• Hyperplasticity of joints, thoracic curvature of keel or funnel-shaped.

The most common disorders associated with Down syndrome are cognitive impairment of ( impaired communication).Cognitive development is often delayed, and all people with Down's syndrome have difficulty learning throughout their lives. As an additional 21st chromosome leads to cognitive impairment, it is not entirely clear. The average size of the human brain with Down syndrome differs little from a healthy person, but scientists have discovered changes in the structure and function of certain areas of the brain, such as the hippocampus and the cerebellum. Especially the hippocampus changes, which is responsible for learning and memory. Scientists use human studies in animal models with Down syndrome to find out which specific genes on the 21st chromosome lead to different aspects of cognitive impairment.

In addition to cognitive impairment, the most common diseases associated with Down syndrome are congenital heart defects .About half of all people with Down syndrome are born with heart disease, often with an atrioventricular defect of the interatrial septum. Other common heart defects include an interventricular septal defect, an interatrial septal defect, a Fallot tetrad and an open arterial duct. Some cases require surgery immediately after birth to correct heart defects.

Gastrointestinal diseases of are also often associated with Down's syndrome, especially esophageal atresia, tracheoesophageal fistula, duodenal atresia or stenosis, Hirschsprung's disease, and unperforated anus. People with Down's syndrome have a higher risk of developing celiac disease. Corrective surgery is sometimes necessary for the gastrointestinal tract.

Some types of cancer are more common in people with Down's syndrome, such as acute lymphoblastic leukemia( a type of blood cancer), myeloid leukemia, and testicular cancer. Solid tumors, on the other hand, are rarely found in this population group.

Patients with Down's syndrome have a number of predispositions to such conditions as hearing loss, frequent infections of the middle ear( otitis media), thyroid pathology( hypothyroidism), cervical spine instability, visual impairment, sleep apnea, obesity, constipation, infantile spasms,seizures, dementia and early onset of Alzheimer's disease.

About 18% to 38% of people with Down's syndrome have mental or behavioral disorders, such as: autism spectrum disorders, attention deficit and hyperreactivity, depression, stereotypic motor disorders and obsessive-compulsive disorders.

Methods of Prenatal Diagnosis of Down Syndrome.

Several options for non-invasive screening are offered to parents. If Down's syndrome is suspected in connection with the results of screening, formally the diagnosis can be made before the baby is born. This gives parents time to collect information about Down's syndrome before giving birth and the opportunity to take action in the event of complications.

Prenatal screening is currently presented by a test for alpha-fetoprotein( AFP) and ultrasound technique. These methods can assess the risk of Down syndrome, but they can not confirm it with a 100% guarantee.

The most widely used AFP screening test. During the period from 15 to 20 weeks of pregnancy, take a small sample of blood from the mother and examine. The levels of AFP and three hormones, which are called unconjugated estriol, human chorionic gonadotropin, and inhibin-A are measured in a blood sample. If AFP and hormone levels change, Down's syndrome can be suspected, but not confirmed. In addition, the normal test result does not exclude Down Syndrome. Also measure the thickness of the occipital fold in the neck with ultrasound. This test is performed between 11 and 13 weeks of pregnancy. In combination with the mother's age, this test identifies about 80% of the probability of Down's syndrome. During the 18th and 22nd week of pregnancy, you can see additional markers that can be found in a fetus with Down syndrome: measure the length of the humerus and femur, the size of the bridge of the nose, the size of the renal pelvis, small bright spots on the heart( ultrasound signs of malformations), largethe gap between the first and second toe.

There are more accurate, but invasive techniques for diagnosing Down syndrome. With these techniques, there is a small risk of complications in the form of miscarriage.

1. Amniocentesis is performed between 16 and 20 weeks of gestation. During this procedure, a thin needle is inserted through the abdominal wall and a small sample of amniotic fluid is taken. The sample is analyzed for chromosomal abnormalities.
2. Chorion biopsy is performed between 11 and 12 weeks of gestation. It involves collecting samples of chorionic villi and cells from the placenta either by inserting a needle into the abdominal wall or through a catheter into the vagina. The sample is also analyzed for chromosomal abnormalities.
3. Through-cut cord blood sampling using fine needle biopsy. Blood is examined for chromosomal abnormalities. This procedure is usually carried out after the 18th week of pregnancy.

Treatment of Down's Syndrome

To date, the disease is incurable. Correction only accompanying violations if necessary( heart defects, gastrointestinal tract. ..)

How can you help children and adults with Down's syndrome? Despite the genetic cause of Down syndrome, it is known that there is currently no medicine. It is very important to stimulate, encourage and educate children with Down's syndrome from infancy. Programs for children with special needs that are offered in many countries are able to improve the quality of life as a result of early intervention, including physical therapy, occupational therapy and speech therapy can be very useful. Like all children, children with Down's syndrome must grow and develop in a safe and supportive environment.

Down syndrome forecast

Life expectancy for people with Down syndrome has increased dramatically over the past few decades, as health care and social adaptation have improved significantly. A person with Down's syndrome in good health will on average live up to 55 years or longer.

People with Down's Syndrome live longer than ever before. Due to full integration into society, many adults with Down syndrome now live completely independently of each other, enjoy relationships, work, and contribute to the community.

Doctor therapist Zhumagaziev E.N.