Down syndrome is the most common and well-known chromosomal disorder in humans and the most common cause of mental disability. Next, we will talk about the etiology, diagnosis and treatment of this pathology.
Down syndrome is a type of genetic disorder that inhibits physical growth as well as the development of intellectual abilities.
A physician from England John Langdon Down first described this pathology in 1866. He took a special interest in people with intellectual disabilities. Although he was the first to identify some of the distinguishing characteristics of people with this anomaly, it was not until 1959 that Dr. Jerome Lejeune, who was studying chromosomes, discovered the cause of the syndrome, an extra chromosome 21.
Why are babies born with Down syndrome?
All cells in the human body contain a nucleus, where the genetic material is stored in the genes. Genes carry the codes for all of our inherited traits and are grouped along rod-like structures called chromosomes. Typically, there are 46 chromosomes in the nucleus of each cell, arranged in 23 pairs. One chromosome from a pair is passed on from the father, and the other from the mother.
Down syndrome is a genetic disease in which people have 47 chromosomes in their cells instead of 46. They have an extra chromosome 21.
Typically, in this disorder, a person inherits two chromosome 21 from the mother (instead of one) and one chromosome 21 from the father, so that each cell contains 3 copies of chromosome 21, not 2 (hence this genetic abnormality is also known as trisomy 21). In this disorder, an extra copy of chromosome 21 leads to an increase in the expression of genes located on it. It is believed that the activity of these additional genes leads to many of the manifestations that characterize Down syndrome.
Types of genetic changes
Three genetic variations can cause Down syndrome.
Complete trisomy 21
In about 92% of cases, Down syndrome is caused by an extra chromosome 21 in every cell.
In such cases, an extra chromosome arises during the development of either an egg or a sperm. Therefore, when an egg and a sperm combine to form a fertilized egg, there are three, not two, chromosome 21. As the embryo develops, an additional chromosome is repeated in each cell.
Robertsonian translocation and partial trisomy 21
In some people, parts of chromosome 21 are fused with another chromosome (usually chromosome 14). This is referred to as a Robertson translocation. The person has a normal set of chromosomes, one of them contains additional genes from chromosome 21. The child inherits additional genetic material from chromosome 21 from his parent with a Robertson translocation, and he will have Downism. Robertsonian translocations occur in a small percentage of the disorder.
It is extremely rare that very small fragments of chromosome 21 are included in other chromosomes. This phenomenon is known as partial trisomy 21.
Mosaic trisomy 21
Another small percentage of cases of the syndrome is mosaic. In a mosaic form, some cells in the body have 3 copies of chromosome 21, while the rest are unaffected. For example, a person may have trisomy 21 skin cells while all other cell types are normal. Mosaic Down Syndrome can sometimes go unnoticed because a person with this genetic variation does not necessarily have all the physical characteristics and is often less cognitively impaired than a person with complete trisomy 21. This can lead to misdiagnosis.
Regardless of the genetic variation that causes the syndrome, people with the disorder have an extra critical portion of chromosome 21 in some or all of their cells. The extra genetic material disrupts the normal course of development, causing the symptoms of trisomy 21.
Down syndrome prevalence
About 1 in 800 babies are born with trisomy 21. About 6,000 babies are born with this disorder every year.
There is no test that can be done before conception to determine if a future newborn will have the syndrome. A baby with trisomy 21 can be born to any couple, but the risk increases with the age of the pregnant woman. On the other hand, young women give birth to most children with chromosomal abnormalities. This is determined by the fact that, compared with adult women, younger women are more likely to give birth to children.
Large studies have been conducted to examine the likelihood of having a child with trisomy 21 associated with the mother's age. The following data were obtained:
- in a woman in her 20s, the risk of giving birth to a child with an anomaly is 1 in 1500;
- in a 30-year-old woman - 1 in 800;
- in a woman at 35, the probability rises to 1 in 270;
- at 40 - the probability is 1 in 100;
- a 45-year-old woman has a 1 in 50 chance or more.
The risk of conceiving a child with a chromosomal abnormality is actually greater than the figures given. This is due to the fact that approximately 3/4 of embryos or developing fetuses with a genetic disorder will never reach full development, and therefore a miscarriage will occur.
It was found that from 1989 to 2008 cases of detection of trisomy 21 in the prenatal and postnatal periods became more frequent, despite the small difference in fertility. But the number of babies born with this genetic disorder has dropped slightly due to improvements and wider use of prenatal screening. It has led to an increase in the frequency of detection of the disorder during pregnancy and, as a result, its termination. Without this improved screening, since women tend to have children at an older age, it is believed that the number of live newborns with a genetic abnormality would otherwise almost double.
If a woman previously had a child with such a pathology, then the risk increases by 1% that the second baby will also suffer from this chromosomal abnormality.
Clinical manifestations
While not all people with this disorder have the same physical characteristics, there are some characteristics that commonly occur with this genetic disorder. This is why patients with trisomy 21 have a similar appearance.
Three features that are found in every individual with Down syndrome:
- epicanthosis folds (extra skin of the inner eyelid that gives the eyes an almond shape);
- eye section according to the Mongoloid type;
- brachycephaly (head with a large transverse diameter);
Other features that people with this genetic disorder have (but not all):
- include light spots in the eyes (Brushfield spots);
- small, slightly flat nose;
- small open mouth with protruding tongue;
- low set small ears that can be folded;
- abnormally formed teeth;
- narrow palate;
- tongue with deep cracks;
- short arms and legs;
- not tall in comparison with healthy children of the same age;
- small feet with an increased gap between the thumb and second toe.
None of these physical features are abnormal in themselves, and they do not cause serious problems or cause any pathology. However, if the doctor sees these manifestations together, he is likely to suspect that the child has Down syndrome.
Common pathologies in Down syndrome
In addition to physical appearance, there is an increased risk of a number of medical problems:
Hypotension
Almost all affected infants have weak muscle tone (hypotension), which means that their muscles are weakened and appear somewhat flexible. With this pathology, it will be difficult for a child to learn to roll, sit, stand and speak. In newborns, hypotension can also cause feeding problems.
Due to hypotension, many children have delayed motor development and may develop orthopedic problems. It cannot be cured, but physical therapy can help improve muscle tone.
Visual impairment
Vision problems are common in the syndrome and are likely to increase with age. Examples of such visual disorders are myopia, hyperopia, strabismus, nystagmus (involuntary eye movements with high frequency).
In children with trisomy 21, an eye exam should be done as early as possible because the above problems can be corrected.
Heart defects
About 50 percent of babies are born with heart abnormalities.
Some of these heart defects are mild and can be corrected on their own without medical intervention. Other heart abnormalities are more severe and require surgery or medication.
Loss of hearing
Hearing problems with Down syndrome are not uncommon. Otitis media affects about 50 to 70 percent of children and is a common cause of hearing loss. Deafness, present at birth, occurs in about 15 percent of children with this genetic disorder.
Gastrointestinal disorders
About 5 percent of sick babies will have gastrointestinal problems, such as a narrowing or blockage of the intestines, or a blocked anus. Most of these pathologies can be corrected with surgery.
Lack of nerves in the large intestine (Hirschsprung's disease) is more common in individuals with the syndrome than in the general population, but is still quite rare. There is also a strong link between celiac disease and trisomy 21, which means it is more common in people with the disorder than in healthy individuals.
Endocrine abnormalities
With Down syndrome, hypothyroidism (insufficient production of thyroid hormones) often develops. It can be congenital or acquired, secondary to Hashimoto's thyroiditis (an autoimmune disease).
Hashimoto's thyroiditis, which causes hypothyroidism, is the most common thyroid disease in affected patients. The disease usually begins at school age. Rarely, Hashimoto's thyroiditis leads to hyperthyroidism (overproduction of hormones).
Individuals with the syndrome have an increased risk of developing type I diabetes.
Leukemia
Very rarely, in about 1 percent of cases, an individual may develop leukemia. Leukemia is a type of cancer that affects the blood cells in the bone marrow. Symptoms of leukemia include easy bruising, fatigue, pale complexion, and unexplained fever. Although leukemia is a very serious disease, the survival rate is high. It is usually treated with chemotherapy, radiation, or bone marrow transplants.
Intellectual problems
All individuals with the syndrome have some degree of mental disability. Children tend to learn more slowly and have difficulty with complex reasoning and judgment. It is impossible to predict what level of mental retardation someone born with a genetic disorder will have, although this will become clearer with age.
The IQ range for normal intelligence is 70 to 130. A person is thought to have a mild intellectual disability when their IQ is 55 to 70. The moderately mentally retarded person has an IQ of 40 to 55. Most affected people have an IQ IQ ranges from mild to moderate intellectual disability.
Despite their IQs, people with the syndrome can learn and develop throughout their lives. This potential can be maximized through early intervention, quality education, rewards, and high expectations.
Features of behavior and psychiatric status
In general, natural spontaneity, true kindness, cheerfulness, gentleness, patience and tolerance are characteristic. Some patients show anxiety and stubbornness.
Most affected children do not have any associated psychiatric or behavioral disorders. Up to 38% of children may have mental health problems associated with them. These include:
- attention deficit hyperactivity disorder;
- oppositional defiant disorder;
- autism spectrum disorder;
- obsessive compulsive disorder;
- depression.
Diagnostics
Down syndrome is usually suspected after a baby is born due to a set of unique characteristics. However, a karyotype test (chromosome study) is performed to confirm the diagnosis. This test involves taking a blood sample from a child to look at the chromosomes in the cells. Karyotyping is important to determine the risk of recurrence. When translocating Down syndrome, karyotyping of parents and other relatives is required for correct genetic counseling.
There are tests that doctors can do before the baby is born:
Screening tests
Screening tests determine the likelihood of a fetus having Down syndrome or other diseases, but they do not definitively diagnose a genetic disorder.
Different types of research include:
- blood tests, which are used to measure protein and hormone levels in a pregnant woman. Abnormally increased or decreased levels may indicate a genetic disorder;
- ultrasound can identify congenital heart defects and other structural changes, such as extra skin at the base of the neck, which may indicate the presence of the syndrome.
A combination of blood test and ultrasound results are used to assess the likelihood that the fetus has Down syndrome.
If there is a high probability on these screening tests, or if there is a higher chance due to maternal age, newer non-invasive tests may report a very high (> 99%) or very low (<1%) probability that the fetus has Down syndrome. However, these tests are not diagnostic.
Diagnostic tests
When screening tests have shown a high likelihood of the fetus having a genetic disorder, additional diagnostic tests are done. They can determine if a fetus has Down syndrome with almost 100 percent accuracy. However, because these tests require the use of a needle to obtain a sample from inside the uterus, they carry a slight increased risk of miscarriage and other complications.
The different types of diagnostic testing include:
- Chorionic villus sampling, in which a small sample of the placenta is taken for specific genetic testing. Chorionic biopsy is used to detect any condition that is associated with certain chromosomal abnormalities. This test is usually performed during the first trimester between 10-14 weeks of pregnancy.
- Amniocentesis, a prenatal diagnostic method in which a needle is inserted into the amniotic sac that surrounds the baby. Amniocentesis is most commonly used to detect Down syndrome and other chromosomal abnormalities. This test is usually done in the second trimester after 15 weeks.
Treatment
Since this is a chromosomal abnormality, there is no cure for Down syndrome. Therefore, treatment for the condition focuses on controlling symptoms, intellectual problems, and any medical conditions that people experience throughout their lives.
Treatment may include:
- using drugs to treat common disorders such as hypothyroidism;
- surgery to repair a heart defect or blockage in your bowel
- selection of glasses and / or hearing aids, as poor eyesight and hearing loss are possible.
Most children need physical therapy to tone up their muscles, as the hypotension present will inhibit the development of motor skills. And early intervention, beginning in infancy, is critical to children reaching their full intellectual potential so that they can become as independent as possible when they reach adulthood.
Surgery
Surgery for heart defects
Certain birth defects are found in children with the syndrome. One of these is an atrioventricular septal defect, in which a hole in the heart obstructs normal blood flow. This defect is eliminated by surgery, namely by correcting the hole and, if necessary, restoring any valves in the heart that may not close completely.
People born with this defect need to be monitored by a cardiologist throughout their life.
Surgery for gastrointestinal diseases
Some babies are born with a deformity of the duodenum called duodenal atresia. The defect requires surgery to repair, but is not considered an emergency if there are other more pressing medical problems.
Early intervention system
The sooner children with Down syndrome receive the personalized care and attention they need to address specific health and developmental problems, the more likely they are to reach their full potential.
An early intervention system is a program of therapy, exercise, and interventions to address developmental delays that children with Down syndrome or other disorders may experience.
A variety of therapies can be used in lifelong early intervention programs to promote the highest possible development, independence and productivity. Some of these treatments are listed below.
Physical therapy includes activities and exercises that help build motor skills, build muscle strength, and improve posture and balance.
Physical therapy is especially important in early childhood because physical ability is at the core of other skills. The ability to roll over, crawl and stand up helps infants learn about the world around them and how to interact with it.
The physical therapist will also help the child compensate for physical problems such as low muscle tone in a way that avoids long-term problems. For example, a physical therapist can help a child create an effective gait pattern, rather than one that causes leg pain.
Speech therapy can help children with Down syndrome improve their communication skills and use language more effectively.
Children with trisomy often learn to speak later than their peers. A speech therapist will assist them in developing early communication skills such as sound imitation.
In many cases, affected children understand the language and want to communicate before they can speak. The speech therapist will show your child how to use alternative means of communication until he learns to speak.
Learning to communicate is an ongoing process, so a person with the syndrome may also benefit from speech and language therapy in school and later in life. The specialist should help develop the skills of conversation, pronunciation, reading comprehension, as well as facilitate the study and memorization of words.
Preparation for work involves learning how to find ways to adapt everyday tasks and conditions in accordance with the needs and abilities of a person.
This type of therapy teaches self-care skills such as eating, dressing, writing, and using the computer.
The professional may suggest special tools to help improve day-to-day functioning, such as a pencil that is easier to grasp.
At the high school level, a specialist helps adolescents to identify a profession or occupation that suits their interests and strengths.
Immunization
Proper immunization is extremely important because structural abnormalities make children with the syndrome more susceptible to infections of the upper respiratory tract, ear, nose, and throat. All affected children should receive the standard recommended series of vaccines: DPT, vaccines against polio, Haemophilus influenzae, measles, rubella and mumps.
The hepatitis B vaccine series must start at birth.
Annual influenza vaccination has been proposed as another means of reducing the incidence of otitis media.
A vaccine against pneumococcal infection is also recommended for children from two years of age.
Features of feeding babies
A baby with Down syndrome can be breastfed. Breast milk is generally easier to digest than formula of all types. In addition, affected children who are breastfed suffer less from diseases of the respiratory system, as well as a lower incidence of otitis media, respiratory allergies. Breastfeeding also promotes oral motor development, which is the basis of speech.
Sucking problems associated with hypotension or heart defects can make breastfeeding difficult, especially in premature babies. In this situation, you can bottle feed your baby with expressed milk. Often, after a few weeks, the baby's ability to suck often improves.
If the infant does not gain sufficient body weight while breastfeeding, the formula should be partially added.
Many babies with Down syndrome tend to be "sleepy babies" in their first weeks. Consequently, feeding only on demand can be ineffective both in terms of calories and in meeting the child's vitamin and nutrient needs. In this situation, the infant should be awakened to feed at least every three or two hours if only breastfeeding is used.
When formula feeding, you should also wake your baby at least every three hours to ensure adequate calorie and nutrient intake.
If weight gain is not a problem, or an infant with Down syndrome has a particular medical disorder at this time, no specific formula is recommended.
The infant's diet should be expanded according to the usual schedule. Delayed teething, however, may delay the administration of solid foods. Parents should remember that it takes a lot of patience to teach a child to spoon and drink from a cup.
Conclusion
In recent decades, people with this chromosomal abnormality have noticeably increased life expectancy. Back in 1960, a child with a genetic disorder often did not live to be ten. Now the estimated life expectancy for such people reaches 50-60 years.
Down syndrome cannot be cured, but even with this condition, your child can still be happy as long as you provide the necessary love, care and treatment.
