What do we know about the needs of children with Mosaic Down syndrome and their families?

Sue Buckley, and Gillian Bird

Mosaic Down syndrome is rare and families feel lost when they receive this diagnosis – often weeks or months after the child’s birth. A new association (the International Mosaic Down Syndrome Association) will lead to progress.

Buckley, S, and Bird, G. (2002) What do we know about the needs of children with Mosaic Down syndrome and their families?. Down Syndrome News and Update, 2(3), 97-99. doi:10.3104/practice.179

In October 2003, the first international conference on Mosaic Down Syndrome will be held in Florida, USA, following the recent establishment of an International Mosaic Down Syndrome Association. The establishment of the Association is an important step, for both parents and professionals, as we do not know enough about the effects of Mosaic Down syndrome. The IMDSA website (www.imdsa.com) has provided parents with a chance to share experiences with other parents and if many families worldwide join the Association it will be possible to begin to gain more detailed information on the needs of these children and their families. At present, it is difficult to find enough children in any locality to study their development. The reader is referred to the personal case histories of children on this site as they make clear the uncertainty that families feel when they receive the diagnosis and the very varied developmental profiles of children with Mosaic Down syndrome.

A rare condition

It is estimated that 2 or 3 children in every 100 children diagnosed as having Down syndrome have the Mosaic form. Children with standard Down syndrome have an extra copy of chromosome 21 in every cell and this is the usual profile for some 96 in 100 children with the diagnosis. Children with Mosaic Down syndrome have some cell lines with the extra chromosome and some cell lines that are not affected and have the usual 46 chromosomes. A few children, 1 or 2 in a 100, have the translocation form of Down syndrome, when the extra chromosome 21 material is attached to another chromosome.

What are the effects?

Little is known about the development of children with Mosaic Down syndrome and how it may differ from the development of children with standard Down syndrome, which makes life very difficult for their parents. There are at least two published studies that suggest that, while they have a range of health and developmental difficulties which are similar to children with standard Down syndrome, these difficulties may be less severe. One American study of 30 children
^[1] and one Japanese study of 8 children
^[2] compared them with matched children with standard Down syndrome and their findings suggest that groups of children with Mosaic Down syndrome have a higher average IQ.

However, group averages are not very helpful when the variability of children within the group is large. For example, the average IQ score for the Mosaic Down syndrome group may be 64
^[1] but some children may score 70 or more and some 40 or less. The average IQ for the standard Down syndrome group may be 52, but again some children will score 70 or more and some 40 or less. The range of scores for children with standard Down syndrome and those with Mosaic Down syndrome will, therefore overlap and some children with standard Down syndrome will score higher than some children with Mosaic Down syndrome, even if the averages indicate that the latter group may be less affected as a whole. This is illustrated in
Figure 1.

Figure 1.

An illustration of the overlap of the IQ measures for children with Mosaic and standard Down syndrome. Children with either diagnosis may be represented in
the shaded area.

These studies are rather dated and I do not think that IQ measures have much practical value, but I am using them to illustrate the issues facing parents. An individual child with Mosaic Down syndrome may show less developmental delay than a child with standard Down syndrome or they may not.

The findings of the first American study ^[1] and a more recent study of a larger group of 45 children carried out in the USA by researchers at the Medical College of Virginia, Virginia Commonwealth University,
^[3] can be found on the website of the International Mosaic Down Syndrome Association
(www.imdsa.com). The researchers at Virginia have compared the children with Mosaic Down syndrome with their brothers and sisters and also with children with standard Down syndrome. The progress of the children with Mosaic Down syndrome was delayed compared to their brothers and sisters on all developmental milestones except age of first rolling over, confirming that the presence of Mosaic Down syndrome can be expected to delay development in all areas. When compared with children with standard Down syndrome, there was a tendency for the children with Mosaic Down syndrome to reach all developmental milestones earlier except in the area of speech and language development.

A similar profile to a lesser degree

This study, like the earlier ones, gives the picture of very similar health and developmental difficulties for children with Mosaic Down syndrome but possibly to a lesser degree. The families have made use of the same range of services including speech and language therapy, physiotherapy and occupational therapy. All but two of the children had received early intervention services and of the 30 of school age or older, all but one had benefited from additional support in schools. One child was fully included without support, ten children were fully included with support and most had experienced some inclusion.

Are individual differences linked to cell pattern?

Children with Mosaic Down syndrome can have different patterns of Mosaicism. In order to try to find out why some children are more significantly delayed than others, some researchers have tried to investigate links between the degree of disability and the percentage of trisomic cells (those with 3 copies of chromosome 21) that the child has. For example, some children have only 25% of their cells with the extra chromosome while some have 50% and some have 75% affected cells. It has been suggested that children with a lower percentage of trisomic cells, are less affected by developmental difficulties, but larger studies are needed to explore this issue, before we can be confident that there is such a relationship.

Personal experiences and some difficult issues

We have had the experience of supporting a number of children with Mosaic Down syndrome in the past 20 years, and our evidence would support the view that these children have the same profile of speech, language, verbal short-term memory and learning difficulties but that their delays tend to be less than the children with standard Down syndrome. Some of the children with Mosaic Down syndrome that we know do not actually look as if they have Down syndrome – the usual physical features are not obvious.

This raises some important and difficult social issues and identity issues for both parents and children, which parents have discussed with us. It is likely that no one would realise the child has Down syndrome unless told, even though the child’s developmental delays may be apparent. How are these children going to feel about their identity as adults? Will they want friends to know that they have Down syndrome? Will they feel that they have much in common with other adults with standard Down syndrome? Does it help to tell teachers and other children that they have Down syndrome when they start school? Will they be treated in a more typical way if the diagnosis is not mentioned? One of the parents on the Association’s website states that she decided not to tell others of the diagnosis. These are issues on which readers may have opinions that we would like to share as the implication is that society is still not fully accepting of individuals with Down syndrome and that most people would still rather not look different from the norm. Please write or e-mail if you have a view on this issue.

The conference

If you are the parent of a child with Mosaic Down syndrome, do consider joining the Association. Details of how to join and of how to book for the conference can be found on their websites (www.mosaicdownsyndrome.com
and www.imdsa.com). The conference is being held in Orlando, Florida so attending it could be combined with a visit to Disneyland! Dr. Colleen Jackson from the Virginia research group will be speaking, as well as
Dr Len Leshin, Cindy Knapp (a parent) and others. One of us will also be contributing and we hope to learn a great deal from meeting many families and individuals with Mosaic Down syndrome. We will report on what we learn in a future issue.

References

1. Fisher, K. & Koch, R. (1991). Mental development in Down syndrome mosaicism.
   American Journal of Mental Retardation, 96, 345-351.
2. Ikeda, Y. (1973). Intellectual development of chromosomal mosaic children with Down syndrome.
   Japanese Journal of Special Education, 10, 44-59.
3. Jackson-Cook, C. (1996). Mosaic Down Syndrome Research Study. Department of Human Genetics, Virginia Commonwealth University, P.O. Box 980033, Richmond, VA23298-0033.

Useful websites

www.mosaicdownsyndrome.com

www.imdsa.com

www.ds-health.com/mosaic.htm

Down Syndrome | Boston Children’s Hospital

What is Down syndrome?

Down syndrome is a genetic condition that happens when a child is born with an extra chromosome. The extra chromosome affects the way the child’s brain and body develop, leading to developmental delays, intellectual disability and an increased risk for certain medical issues.

Down syndrome is the most common genetic cause of intellectual disability, affecting approximately 1 in every 700 children. It is named for John Langdon Down, the British physician who first recognized the traits of Down syndrome in 1866.

The chance that a baby will be born with Down syndrome increases with a mother’s age:

• 1 baby out of every 1,000 born to women under age 30
• 1 baby out of every 400 born to women older than 35
• 1 baby out of every 60 born to women older than 42

Some expectant parents choose to undergo prenatal testing to find out in advance if their child will have Down syndrome. These optional tests, performed during pregnancy, can identify a fetus’s sex, age, size and placement in the uterus. They can also detect conditions such as Down syndrome, congenital heart defects, genetic conditions and other birth defects.

Down syndrome and intellectual disability

Most children with Down syndrome have some level of intellectual disability ⎯ usually in the mild to moderate range. People with mild intellectual disability are usually able to learn how to do everyday things like read, hold a job, and take public transportation on their own. People with moderate intellectual disability usually need more support.

Many children with Down syndrome can participate in regular classrooms, though they may need extra help or modifications. Thanks to widespread special education and community programs, more and more people with Down syndrome graduate from high school, attend college and work in their communities.

To help children with Down syndrome reach their highest potential, parents can seek out assistance programs as early as possible. By law, every state must provide developmental and special education services for children with Down syndrome, starting at birth with early Intervention and then continuing with public education until age 21.

Down syndrome and medical problems

Children with Down syndrome can have a variety of health issues. About half are born with a congenital heart defect, a structural problem with the heart that develops during pregnancy.

The most common congenital heart defects in children with Down syndrome include:

Many children with heart defects also develop pulmonary hypertension, a condition that can cause lasting lung damage if left untreated.

Other health issues that commonly affect children with Down syndrome include:

How we care for Down syndrome

The Boston Children’s Hospital Down Syndrome Program is one of the oldest and largest programs for children with Down syndrome and their families. The program is a subspecialty of the Developmental Medicine Center.

From their first visit at Boston Children’s, new parents work with a team of professionals committed to supporting all of their child’s clinical, physical and emotional needs. We provide specialized medical care, resources, support and advocacy for children with Down syndrome from birth through age 22 and regularly make referrals to other specialty clinics at Boston Children’s, depending on a child’s needs. We also help put parents in touch with other families with Down syndrome and connect them to community and educational services appropriate for their child.

For children born with heart defects, our Heart Center is the largest in the United States and one of the most specialized in the world. We provide a full range of care and our specialists have extensive experience treating rare heart problems with results that are among the best in the world.

Support for expecting parents who receive a prenatal diagnosis of Down syndrome

The Down Syndrome Program works closely with the Maternal Fetal Care Center. Depending on a family’s needs, we provide prenatal consultation to answer questions and help expecting parents learn more about Down syndrome. We offer confidential, non-directive counseling for families uncertain about their plans, providing a safe opportunity to gather information and make an informed decision about the pregnancy.

For families with a likely or confirmed diagnosis who plan to continue the pregnancy, the prenatal visit becomes the first clinical visit where we begin to help plan for the baby’s future. We discuss common medical conditions, developmental issues, education and resources in the community.

About Down syndrome — Down Syndrome Guild of Dallas

There are two categories of tests for Down syndrome that can be performed before a baby is born: screening tests and diagnostic tests. Prenatal screens estimate the chance of the fetus having Down syndrome. These tests do not tell you for sure whether your fetus has Down syndrome; they only provide a probability. Diagnostic tests, on the other hand, can provide a definitive diagnosis with almost 100% accuracy.

There is an extensive menu of prenatal screening tests now available for pregnant women. Most screening tests involve a blood test and an ultrasound (sonogram). The blood tests (or serum screening tests) measure quantities of various substances in the blood of the mother. Together with a woman’s age, these are used to estimate her chance of having a child with Down syndrome. These blood tests are often performed in conjunction with a detailed sonogram to check for “markers” (characteristics that some researchers feel may have a significant association with Down syndrome). New advanced prenatal screens are now able to detect chromosomal material from the fetus that is circulating in the maternal blood. These tests are not invasive (like the diagnostic tests below), but they provide a high accuracy rate. Still, all of these screens will not definitively diagnose Down syndrome. Prenatal screening and diagnostic tests are now routinely offered to women of all ages.

The diagnostic procedures available for prenatal diagnosis of Down syndrome are chorionic villus sampling (CVS) and amniocentesis. These procedures, which carry up to a 1% risk of causing a spontaneous termination (miscarriage), are nearly 100% accurate in diagnosing Down syndrome. Amniocentesis is usually performed in the second trimester between 15 and 20 weeks of gestation, CVS in the first trimester between 9 and 14 weeks.

AT BIRTH

Down syndrome is usually identified at birth by the presence of certain physical traits: low muscle tone, a single deep crease across the palm of the hand, a slightly flattened facial profile and an upward slant to the eyes. Because these features may be present in babies without Down syndrome, a chromosomal analysis called a karyotype is done to confirm the diagnosis. To obtain a karyotype, doctors draw a blood sample to examine the baby’s cells. They photograph the chromosomes and then group them by size, number, and shape. By examining the karyotype, doctors can diagnose Down syndrome. Another genetic test called FISH can apply similar principles and confirm a diagnosis in a shorter amount of time.

How Will Having Down syndrome Affect My Child?

Down syndrome is a lifelong condition. Babies born with Down syndrome will grow and develop like all other babies, but those with Down syndrome generally develop at a somewhat slower pace. Children with Down syndrome may be delayed in achieving milestones such as walking, talking, and eating compared to neurotypical children. Individuals with Down syndrome possess varying degrees of cognitive delays, but the effect is usually mild to moderate and is not indicative of the many strengths and talents that each individual possesses. People with Down syndrome may have an increased risk for certain medical conditions such as congenital heart defects, respiratory and hearing problems, Alzheimer’s disease, childhood leukemia, and thyroid conditions. However, many of these conditions are treatable, and people with Down syndrome lead long, healthy lives. Life expectancy for people with Down syndrome has increased dramatically in recent decades – from 25 in 1983 to 60 and older today.

Individuals with Down syndrome are becoming increasingly integrated into society and the community. People with Down syndrome attend school, work, participate in decisions that affect them, and contribute to society in many wonderful ways. Quality educational programs, a stimulating home environment, good health care, and positive support from family, friends, and the community enable people with Down syndrome to develop their full potential and lead fulfilling lives.

We Have Received a Down Syndrome Diagnosis. What Do We Do Now?

We know that receiving a Down syndrome diagnosis whether prenatally or after birth can often be unexpected and overwhelming for new families. The Down Syndrome Guild of Dallas is here to support you and your family no matter where you are on your Down syndrome journey. The Down Syndrome Guild has a New and Expectant Parent Program (in English and Spanish) where a trained First Call Family, a parent of a child with Down syndrome, will contact you to welcome you to the DSG community, answer your questions, and tell you about related programs and services. You can also request an informational Welcome Packet and sign up to receive our email newsletters. Please contact us at (214) 267-1374 or visit the New and Expectant Parent webpage for more details.

How Can the Down Syndrome Guild of Dallas Help My Family?

The Down Syndrome Guild of Dallas offers year-round programs for people with Down syndrome of all ages and their family members. Programs include the New and Expectant Parent program, Grupo de Familias Unidas for Spanish speaking families, social gatherings like picnics, holiday celebrations, and supper club, skill-building classes like music & movement and book club, and recreational camps like iCan Bike and iCan Swim.

The Down Syndrome Guild additionally offers educational seminars throughout the year for parents, guardians, and community professionals. The organization has an extensive resource library and provides resources and referrals relating to a variety of topics as well.

Through Down Syndrome Guild social, educational, and recreational programs, people with Down syndrome and their families connect to form lifelong friendships and learn from experts in their respective fields to support development throughout the lifespan. For more information on DSG programs for all ages as well as upcoming events please visit Overview of Programs and Calendar.

Overview of Down syndrome | Anna’s Angels

From the National Down Syndrome Society

What Is Down Syndrome?

In every cell in the human body there is a nucleus, where genetic material is stored in genes. Genes carry the codes responsible for all of our inherited traits and are grouped along rod-like structures called chromosomes. Typically, the nucleus of each cell contains 23 pairs of chromosomes, half of which are inherited from each parent. Down syndrome occurs when an individual has a full or partial extra copy of chromosome 21.

This additional genetic material alters the course of development and causes the characteristics associated with Down syndrome. A few of the common physical traits of Down syndrome are low muscle tone, small stature, an upward slant to the eyes, and a single deep crease across the center of the palm – although each person with Down syndrome is a unique individual and may possess these characteristics to different degrees, or not at all.

How Common Is Down Syndrome?

One in every 691 babies in the United States is born with Down syndrome, making Down syndrome the most common genetic condition. Approximately 400,000 Americans have Down syndrome and about 6,000 babies with Down syndrome are born in the United States each year.

When Was Down Syndrome Discovered?

For centuries, people with Down syndrome have been alluded to in art, literature and science. It wasn’t until the late nineteenth century, however, that John Langdon Down, an English physician, published an accurate description of a person with Down syndrome. It was this scholarly work, published in 1866, that earned Down the recognition as the “father” of the syndrome. Although other people had previously recognized the characteristics of the syndrome, it was Down who described the condition as a distinct and separate entity.

In recent history, advances in medicine and science have enabled researchers to investigate the characteristics of people with Down syndrome. In 1959, the French physician Jérôme Lejeune identified Down syndrome as a chromosomal condition. Instead of the usual 46 chromosomes present in each cell, Lejeune observed 47 in the cells of individuals with Down syndrome. It was later determined that an extra partial or whole copy of chromosome 21 results in the characteristics associated with Down syndrome. In the year 2000, an international team of scientists successfully identified and catalogued each of the approximately 329 genes on chromosome 21. This accomplishment opened the door to great advances in Down syndrome research.

Are There Different Types of Down Syndrome?

There are three types of Down syndrome: trisomy 21 (nondisjunction), translocation and mosaicism.

TRISOMY 21 (NONDISJUNCTION)
Down syndrome is usually caused by an error in cell division called “nondisjunction.” Nondisjunction results in an embryo with three copies of chromosome 21 instead of the usual two. Prior to or at conception, a pair of 21st chromosomes in either the sperm or the egg fails to separate. As the embryo develops, the extra chromosome is replicated in every cell of the body. This type of Down syndrome, which accounts for 95% of cases, is called trisomy 21.

MOSAICISM
Mosaicism occurs when nondisjunction of chromosome 21 takes place in one – but not all – of the initial cell divisions after fertilization. When this occurs, there is a mixture of two types of cells, some containing the usual 46 chromosomes and others containing 47. Those cells with 47 chromosomes contain an extra chromosome 21.

Mosaicism accounts for about 1% of all cases of Down syndrome. Research has indicated that individuals with mosaic Down syndrome may have fewer characteristics of Down syndrome than those with other types of Down syndrome. However, broad generalizations are not possible due to the wide range of abilities people with Down syndrome possess.

TRANSLOCATION
Translocation accounts for about 4% of all cases of Down syndrome. In translocation, part of chromosome 21 breaks off during cell division and attaches to another chromosome, typically chromosome 14. While the total number of chromosomes in the cells remain 46, the presence of an extra part of chromosome 21 causes the characteristics of Down syndrome.

What Causes Down Syndrome?

Regardless of the type of Down syndrome a person may have, all people with Down syndrome have an extra, critical portion of chromosome 21 present in all or some of their cells. This additional genetic material alters the course of development and causes the characteristics associated with Down syndrome.

The cause of nondisjunction is currently unknown, but research has shown that it increases in frequency as a woman ages. However, due to higher birth rates in younger women, 80% of children with Down syndrome are born to women under 35 years of age. There is no definitive scientific research that indicates that Down syndrome is caused by environmental factors or the parents’ activities before or during pregnancy.

The additional partial or full copy of the 21st chromosome which causes Down syndrome can originate from either the father or the mother. Approximately 5% of the cases have been traced to the father.

What Is the Likelihood of Having a Child with Down Syndrome?

Down syndrome occurs in people of all races and economic levels, though older women have an increased chance of having a child with Down syndrome. A 35 year old woman has about a one in 350 chance of conceiving a child with Down syndrome, and this chance increases gradually to 1 in 100 by age 40. At age 45 the incidence becomes approximately 1 in 30. The age of the mother does not seem to be linked to the risk of translocation.

Since many couples are postponing parenting until later in life, the incidence of Down syndrome conceptions is expected to increase. Therefore, genetic counseling for parents is becoming increasingly important. Still, many physicians are not fully informed about advising their patients about the incidences of Down syndrome, advancements in diagnosis, and the protocols for care and treatment of babies born with Down syndrome.

Does Down Syndrome Run in Families?

All 3 types of Down syndrome are genetic conditions (relating to the genes), but only 1% of all cases of Down syndrome have a hereditary component (passed from parent to child through the genes). Heridity is not a factor in trisomy 21 (nondisjunction) and mosaicism. However, in one third of cases of Down syndrome resultuing from translocation there is a heriditary compontent – accounting for about 1% of all cases of Down syndrome.

The age of the mother does not seem to be linked to the risk of translocation. Most cases are sporadic – chance – events. However, in about one third of cases, one parent is a carrier of a translocated chromosome.

What Is the Likelihood of Having a Second Child with Down Syndrome?

Once a woman has given birth to a baby with trisomy 21 (nondisjunction) or translocation, it is estimated that her chances of having another baby with trisomy 21 is 1% greater than her chances by age alone.

The risk of recurrence of translocation is about 3% if the father is the carrier and 10-15% if the mother is the carrier. Genetic counseling can determine the origin of translocation.

How Is Down Syndrome Diagnosed?

PRENATALLY
There are two categories of tests for Down syndrome that can be performed before a baby is born: screening tests and diagnostic tests. Prenatal screens estimate the chance of the fetus having Down syndrome. Most of these tests only provide a probability. Diagnostic tests can provide a definitive diagnosis with almost 100% accuracy.

Most screening tests involve a blood test and an ultrasound (sonogram). The blood tests (or serum screening tests) measure quantities of various substances in the blood of the mother. Together with a woman’s age, these are used to estimate her chance of having a child with Down syndrome. These blood tests are often performed in conjunction with a detailed sonogram to check for “markers” (characteristics that some researchers feel may have a significant association with Down syndrome). New advanced prenatal screens are now able to detect chromosomal material from the fetus that is circulating in the maternal blood. These tests are not invasive (like the diagnostic tests below), but they provide a high accuracy rate. Still, all of these screens will not definitively diagnose Down syndrome. Prenatal screening and diagnostic tests are now routinely offered to women of all ages.

The diagnostic procedures available for prenatal diagnosis of Down syndrome are chorionic villus sampling (CVS) and amniocentesis. These procedures, which carry up to a 1% risk of causing a spontaneous termination (miscarriage), are practically 100% accurate in diagnosing Down syndrome. Amniocentesis is usually performed in the second trimester after 15 weeks of gestation, CVS in the first trimester between 9 and 11 weeks.

AT BIRTH
Down syndrome is usually identified at birth by the presence of certain physical traits: low muscle tone, a single deep crease across the palm of the hand, a slightly flattened facial profile and an upward slant to the eyes. Because these features may be present in babies without Down syndrome, a chromosomal analysis called a karyotype is done to confirm the diagnosis. To obtain a karyotype, doctors draw a blood sample to examine the baby’s cells. They use special tools to photograph the chromosomes and then group them by size, number, and shape. By examining the karyotype, doctors can diagnose Down syndrome. Another genetic test called FISH can apply similar principles and confirm a diagnosis in a shorter amount of time.

What Impact Does Down Syndrome Have on Society?

Individuals with Down syndrome are becoming increasingly integrated into society and community organizations, such as school, health care systems, work forces, and social and recreational activities. Individuals with Down syndrome possess varying degrees of cognitive delays, from very mild to severe. Most people with Down syndrome have cognitive delays that are mild to moderate.

Due to advances in medical technology, individuals with Down syndrome are living longer than ever before. In 1910, children with Down syndrome were expected to survive to age nine. With the discovery of antibiotics, the average survival age increased to 19 or 20. Now, with recent advancements in clinical treatment, most particularly corrective heart surgeries, as many as 80% of adults with Down syndrome reach age 60, and many live even longer. More and more Americans are interacting with individuals with Down syndrome, increasing the need for widespread public education and acceptance.

Get more facts at the National Down Syndrome Society.

Down Syndrome (Trisomy 21) in Children

What is Down syndrome in children?

Down syndrome is a genetic disorder. It is also called trisomy 21. It includes certain birth defects, learning problems, and facial features. A child with Down syndrome also may have heart defects and problems with vision and hearing. How severe or mild these problems are varies from child to child.                        

Down syndrome is one of the most common genetic birth defects. It affects about 1 in 700 babies. Adults with Down syndrome may live about 60 years, but this can vary.

What causes Down syndrome in a child?

When a baby is conceived, a normal egg cell and normal sperm cell start with 46 chromosomes. The egg and sperm cells then divide in half. The egg and sperm cells then have 23 chromosomes each. When a sperm with 23 chromosomes fertilizes an egg with 23 chromosomes, the baby will then have a complete set of 46 chromosomes. Half are from the father and half are from the mother.

But sometimes an error occurs when the 46 chromosomes are being divided in half. An egg or sperm cell may keep both copies of chromosome number 21, instead of just 1 copy. If this egg or sperm is fertilized, then the baby will have 3 copies of chromosome number 21. This is called trisomy 21.

Sometimes the extra number 21 chromosome or part of it is attached to another chromosome in the egg or sperm. This may cause translocation Down syndrome. This is the only form of Down syndrome that may be inherited from a parent.

A rare form is called mosaic trisomy 21. This is when an error in cell division happens after the egg is fertilized. People with this syndrome have both normal cells and some cells with an extra chromosome number 21.

Which children are at risk for Down syndrome?

A mother’s age at her child’s birth is a factor linked to the risk of having a baby with Down syndrome. This risk increases with each year of age, especially after age 35. But younger women are more likely to have babies than older women. Therefore, most babies with Down syndrome are born to women younger than 35.

What are the symptoms of Down syndrome in a child?

Symptoms can occur a bit differently in each child. They can include:

• Eyes that slant up

• Small ears that may fold over slightly at the top

• Small mouth that makes the tongue seem large

• Small nose with a flattened bridge

• Short neck

• Small hands with short fingers

• Two instead of 3 palm creases, including one across the palm and one around the base of the thumb

• Short height

• Loose joints

Most children with Down syndrome will have some but not all of these features.

Down syndrome can also include:

How is Down syndrome diagnosed in a child?

Chromosome problems such as Down syndrome can often be diagnosed before birth. Screening tests are often done first. These often combine a blood test with an ultrasound. A screening test tells you and your healthcare provider if you have a greater or lesser chance of having Down Syndrome. They don’t make a diagnosis. A diagnostic test is more invasive and risky. But it generally can find the disorder.

The screening ultrasound looks at the amount of amniotic fluid present. Extra fluid means there is a problem. The blood test looks at many substances in the blood, such as MS-AFP, Triple Screen, and Quad-screen, to show a possible risk. These tests look at various levels of certain substances such as alpha-fetoprotein, human chorionic gonadotropin, estriol to determine risk. Fetal ultrasound during pregnancy can also show the possibility of Down syndrome. But ultrasound is not 100% accurate. Problems from Down syndrome may not be seen with ultrasound.

Diagnostic tests are done by looking at cells in the amniotic fluid or from the placenta. These tests include:

• Chorionic villus sampling. This test examines cells from the placenta.

• Amniocentesis. This tests the fluid from the sac surrounding the baby (amniotic fluid).

• Percutaneous umbilical blood sampling. This tests blood from the umbilical cord.

All 3 of these tests look for characteristic changes in the chromosomes that occur in a Down syndrome diagnosis.

After birth, your baby may be diagnosed with a physical exam. The healthcare provider may also take a blood sample. This is checked in a lab to find the extra chromosome.

How is Down syndrome treated in a child?

There is no cure for Down syndrome. But a child with Down syndrome may need treatment for problems such as:               

• Heart defects. About half of babies with Down syndrome have heart defects. Some defects are minor. These can be treated with medicines or they will fix themselves on their own. Others may need surgery. All babies with Down syndrome should have an echocardiogram (heart ultrasound) and be looked at by a pediatric cardiologist. This exam and test should be done shortly after birth. This is so that any heart defects can be found and treated correctly.

• Intestinal problems. Some babies with Down syndrome are born with intestinal problems that need surgery.

• Vision problems. Common problems include crossed eyes, nearsightedness or farsightedness, and cataracts. Most eyesight problems can be made better with eyeglasses, surgery, or other treatments. Your child should see an eye doctor (pediatric ophthalmologist) before they turn 1 year old.

• Hearing loss. This is caused by fluid in the middle ear, a nerve defect, or both. Your child should get regular hearing tests so any problems can be treated early. This will help with language development.

• Other health problems. Children with Down syndrome may have thyroid problems and leukemia. They also tend to have many colds, as well as bronchitis and pneumonia. Your child should get regular medical care and stay up to date on vaccines.

• Learning problems. These vary widely from child to child. They can be mild, moderate, or severe. But most learning problems are mild to moderate. Many children will receive early intervention and special education.

Some people claim that giving high-dose vitamins to children with Down syndrome will improve their learning and development problems. No studies have proved that this works.

Talk with your child’s healthcare providers about the risks, benefits, and possible side effects of all treatments.

What are possible complications of Down syndrome in a child?

Complications of Down syndrome vary depending on the body organ affected and the severity of the problem. Problems include certain birth defects, learning problems, and facial features. A child with Down syndrome also may have heart defects and problems with vision and hearing. How severe the complications are varies from child to child. Treatment will also vary depending on the body organ affected and the severity of the problem. Your child’s healthcare provider will discuss treatment options with you.

What can I do to help prevent Down syndrome in my child?

Researchers don’t know how to prevent the chromosome errors that cause this disorder. There is no reason to believe parents can do anything to cause or prevent Down syndrome in their child.

For women who have had one child with Down syndrome, the chance of having another baby with Down syndrome depends on several things. Age is one factor. Most babies with Down syndrome are born to women younger than 35. This is because women under 35 have more babies than women over 35.

Your healthcare provider may refer you to a genetic counselor. This expert can explain the results of chromosome tests in detail. They can talk about risks for future pregnancies and what tests are available to diagnose chromosome problems before a baby is born.

Some medical organizations advise that all pregnant women of any age be offered screening for Down syndrome. Talk with your healthcare provider about this prenatal screening test.

How can I help my child live with Down syndrome?

Children with Down syndrome can often do most things that any young child can do. They can walk, talk, dress themselves, and be toilet trained. But they often do these things at a later age than other children. The exact ages of these development milestones is different for each child. Early intervention programs that begin when a child is a baby can help the child reach their potential.

A child with Down syndrome can go to school. Special programs beginning in the preschool years help children with Down syndrome develop skills as fully as possible. Many children are helped with early intervention and special education. They can also enter a regular classroom. Many children will learn to read and write. They can take part in childhood activities, both at school and in their community.

Your child may need physical, occupational, and speech therapy to help with their development. Talk with your child’s healthcare provider, other families, and national Down syndrome support agencies to learn what to expect with Down syndrome. You can also learn what may be helpful in raising a child with Down syndrome. 

Special work programs are designed for adults with Down syndrome. Many adults with this disorder can hold regular jobs. More and more adults with Down syndrome live semi-independently in community group homes. They take care of themselves, do household chores, develop friendships, do leisure activities, and work in their communities.

Some people with Down syndrome marry. Most men with Down syndrome can’t father a child. In any pregnancy, a woman with Down syndrome has a 1 in 2 chance of conceiving a child with Down syndrome. Many of the pregnancies are miscarried.

When should I call my child’s healthcare provider?

Call the healthcare provider if your child has:

Key points about Down syndrome in children

• Down syndrome (trisomy 21) is a genetic disorder. It includes certain birth defects, learning problems, and facial features. A child with Down syndrome also may have heart defects and problems with vision and hearing.

• A mother’s age at her child’s birth is the only factor linked to the risk of having a baby with Down syndrome. This risk increases with each year of age, especially after age 35.

• There is no reason to believe parents can do anything to cause or prevent Down syndrome in their child. Researchers don’t know how to prevent the chromosome errors that cause this disorder.

• Down syndrome can often be diagnosed before birth. After birth, your baby may be diagnosed with a physical exam. The healthcare provider may also take a blood sample.

• There is no cure for Down syndrome, but treatment is available to help your child.

• Your child may need physical, occupational, and speech therapy to help with their development. Many children are helped with early intervention and special education.

Next steps

Tips to help you get the most from a visit to your child’s healthcare provider:

• Know the reason for the visit and what you want to happen.

• Before your visit, write down questions you want answered.

• At the visit, write down the name of a new diagnosis, and any new medicines, treatments, or tests. Also write down any new instructions your provider gives you for your child.

• Know why a new medicine or treatment is prescribed and how it will help your child. Also know what the side effects are.

• Ask if your child’s condition can be treated in other ways.

• Know why a test or procedure is recommended and what the results could mean.

• Know what to expect if your child does not take the medicine or have the test or procedure.

• If your child has a follow-up appointment, write down the date, time, and purpose for that visit.

• Know how you can contact your child’s provider after office hours. This is important if your child becomes ill and you have questions or need advice.

What people with Down Syndrome can teach us about cardiopulmonary disease

Abstract

Down syndrome is the most common chromosomal abnormality among live-born infants. Through full or partial trisomy of chromosome 21, Down syndrome is associated with cognitive impairment, congenital malformations (particularly cardiovascular) and dysmorphic features. Immune disturbances in Down syndrome account for an enormous disease burden ranging from quality-of-life issues (autoimmune alopecia) to more serious health issues (autoimmune thyroiditis) and life-threatening issues (leukaemia, respiratory tract infections and pulmonary hypertension). Cardiovascular and pulmonary diseases account for ∼75% of the mortality seen in persons with Down syndrome. This review summarises the cardiovascular, respiratory and immune challenges faced by individuals with Down syndrome, and the genetic underpinnings of their pathobiology. We strongly advocate increased comparative studies of cardiopulmonary disease in persons with and without Down syndrome, as we believe these will lead to new strategies to prevent and treat diseases affecting millions of people worldwide.

Abstract

This review summarises the cardiopulmonary and immune challenges faced by individuals with Down syndrome http://ow.ly/tlGU306iMkG

Introduction

Down syndrome is the most common chromosomal abnormality worldwide, with an incidence of between 1 in 700 and 1 in 800 live births [1]. Across Europe, ∼9000 babies are born with Down syndrome annually. It is a multisystem condition caused by the presence of a third copy of part or all of human chromosome 21 (Hsa21). Invariably, Down syndrome is associated with a spectrum of craniofacial abnormalities, hypotonia and cognitive impairment, as well as early-onset Alzheimer’s dementia [2]. Other medical problems are common in persons with Down syndrome: gastrointestinal malformations, congenital heart defects, respiratory disease, autoimmunity, thyroid dysfunction and haematological disorders [3] (figure 1). Persons with Down syndrome are resistant to the development of solid tumours and coronary atherosclerotic disease (CAD). Unfortunately, the mechanisms responsible for predisposition or resistance to these conditions are poorly understood. ∼45–50% of all newborns with Down syndrome have a congenital heart defect (CHD), usually atrioventricular septal defect [4], depending on ethnicity and sex [5]. Despite elevated risk factors of lipid metabolism [6] and obesity [7], the incidence of atherosclerotic disease in adults with Down syndrome is low [8, 9]. Thyroid-related cardiac dysfunction is common in Down syndrome [10]. Lung disease accounts for 54% of hospital admissions in Down syndrome [11], and average length of admission is two to three times longer than in individuals without the syndrome [12]. For persons with Down syndrome aged <3 years, respiratory illnesses are the most common cause of hospital admissions [12]. Persons with Down syndrome have increased frequency of respiratory tract infection [13] and acute respiratory distress syndrome [14]. Respiratory disease is the most common cause of death in persons with Down syndrome of any age [15]. There is a large population of persons with Down syndrome in Europe, the United States, and worldwide. A large Down syndrome population, combined with the high incidence of cardiopulmonary disease in Down syndrome, is therefore associated with significant morbidity, mortality and cost. We have a unique opportunity to advance the science and treatment of cardiopulmonary disease for all individuals by studying these diseases in the context of Down syndrome.

FIGURE 1

Heart and lung diseases are the leading causes of death for persons with Down syndrome. Pneumonia and infectious lung disease, congenital heart defect (CHD) and circulatory disease (vascular diseases not including CHD or ischaemic heart disease) account for ∼75% of all deaths in persons with Down syndrome. Interestingly, ischaemic cardiovascular disease accounts for only ∼7% of deaths in Down syndrome, compared to the typical population mortality rate of ∼30% (not shown). Reproduced and modified from [38] with permission from the publisher.

In this review we highlight the unique opportunity provided by persons with Down syndrome to the broader biomedical research community. CAD is the leading global cause of death, and caused >1.8 million deaths (42% of total deaths) in 2014 in Europe alone [16], but for reasons that are not clear, atherosclerotic disease and CAD are rare in Down syndrome. Respiratory diseases, excluding lung cancer, are responsible for ∼15% of all deaths in Europe [17]. Of the 10 leading causes of infant mortality, four were lung diseases, accounting for ∼30% of childhood deaths. Respiratory disease is a major medical problem for persons with Down syndrome. These numbers reinforce the notion that a better understanding of why those with Down syndrome get more lung disease and congenital heart defects, but much less cardiovascular and atherosclerotic disease, will greatly benefit millions of people worldwide. Indeed, the study of outliers or phenotypic extremes in biology has yielded paradigm-shifting breakthroughs (e.g. thermophilic bacteria and thermostable enzymes for PCR [18] and the search for HIV-AIDS resistance genes [19]).

Respiratory disease in Down syndrome

Respiratory disease constitutes a large proportion of the morbidity in Down syndrome (table 1), and contributes to reduced life expectancy. Mortality rates for respiratory illnesses are significantly elevated in children [20] and in adults [21, 22] with Down syndrome. In Down syndrome, respiratory failure is a predictor of mortality [22]. There are limitations and potential biases in these studies, including data collection methods, lack of differentiation between primary diagnoses versus secondary diagnoses, and lack of long-term follow-up research. Nevertheless, respiratory disease contributes greatly to morbidity and mortality in Down syndrome.

TABLE 1

Respiratory complications of Down syndrome

Most of what is known about respiratory disease in Down syndrome comes from studies in the paediatric population. Studies in adults with Down syndrome with lung disease are sparse. Respiratory disease in Down syndrome can be organised into conditions affecting the upper airways, the lower airways and the pulmonary vasculature. The upper respiratory tract in persons with Down syndrome is often narrow due to congenital and associated conditions [23–25]. The trachea is often smaller in children with Down syndrome [26], and tracheal bronchus contributes to recurrent pneumonia [27, 28]. Airway malacia causes obstruction in >50% of children with Down syndrome, with other causes more prevalent in adults [29, 30]. These structural factors combine with hypotonia and obesity to increase the likelihood of proximal airway obstruction [31]. Sleep-related breathing disorders such as obstructive sleep apnoea occur in 39–79% of children with Down syndrome [32, 33]. In some patients with sleep apnoea, chronic intermittent hypoxia and respiratory acidosis contribute to pulmonary hypertension and cor pulmonale [34]. Infection of the upper airway, typically viral croup, is common in adults and children with Down syndrome. In a 20-year study of 239 children with Down syndrome, 23% presented with symptoms of stridor and 18% had persistent chronic croup [35].

Recurrent lower respiratory tract infection is common in persons with Down syndrome, especially children. Respiratory disease accounts for 43–78% of intensive care unit admissions, and 50% of those required ventilation support [12, 36, 37]. Respiratory illness is second only to CHD in mortality of individuals with Down syndrome at any age [38]. The average hospital stay due to lower respiratory illness is longer for children with Down syndrome [11]. One of the most important causes of lower respiratory tract infection is respiratory syncytial virus (RSV). Down syndrome is an independent risk factor for RSV bronchiolitis [36, 39]. Congenital abnormalities of the respiratory tract contribute not only to infection but also to chronic aspiration [37]. Delayed motor function and structural anomalies of the oral–nasal passages contribute to chronic aspiration manifested by persistent cough, wheezing and pneumonia [37]. Inherent deficiencies in innate and acquired immunity contribute to predisposition to respiratory tract infection. Poor response to vaccination potentially contributes to respiratory infection [40], as does decreased ciliary beat frequency, although ciliary ultrastructure in Down syndrome is normal [41].

Respiratory disease in Down syndrome can involve not only the airways but also the pulmonary vasculature. Pulmonary vascular diseases are wide-ranging in their aetiology and pathogenesis. Pulmonary embolism and pulmonary oedema are commonly found on computed tomography in pulmonary vascular diseases such as CHD, altitude sickness and pulmonary artery hypertension (PAH) [42–46]. Embolism and oedema in the lung secondary to left heart disease are thought to derive from changes in endothelial permeability and are probably related to potassium and calcium channel disturbances [47–49]. The lung vascular histopathology of persons with Down syndrome includes overall immaturity, double capillary networks and prominent intrapulmonary bronchopulmonary anastomoses [50–52]. In the fetal Down syndrome lung vasculature, overabundance of anti-angiogenic factors such as endostatin, collagen-4A3, amyloid protein precursor and tissue inhibitor of matrix metalloproteinase-3 may help to explain decreased vascularity and predisposition to pulmonary hypertension [53].

The high incidence of CHD in children with Down syndrome (discussed in detail later) is a major contributor to the incidence of group 1 PAH. In persons with Down syndrome and CHD with a left–right shunt, there is an imbalance in vasoactive mediators which favours vasoconstriction, platelet aggregation and cell proliferation in the pulmonary vasculature [54]. Infants with Down syndrome have a high rate of PAH that is disproportionate for their age [55–57], and ∼30% of adults with Down syndrome have septal defects and higher associated mortality compared to those without Down syndrome [58]. Persistent pulmonary hypertension of the newborn, another group 1 PAH disease, is quite prevalent in Down syndrome [59–61]. The combination of upper respiratory tract malformations, alveolar capillary dysplasia, hypoxia and hypercapnia may collectively promote development of pulmonary hypertension [62, 63]. Importantly, there have been no randomised controlled trials in Down syndrome with PAH examining response to vasodilator therapy [64, 65]. The available data suggest that persons with Down syndrome are equally as responsive as PAH patients without Down syndrome to endothelin receptor antagonists such as bosentan [64–68], although the 6-min walk test may not be an effective end-point [69]. Despite the high incidence of CHD in individuals with trisomy 21, pulmonary thrombosis does not appear to be a cause of morbidity or mortality in Down syndrome [70–74]. Children with Down syndrome are susceptible to rapid development of high-altitude pulmonary oedema, even at low altitudes (∼2000 m) [75]. Interestingly, the oedema was not secondary to left ventricular dysfunction. This may be due to increased pulmonary vasoreactivity and pulmonary vascular overperfusion and injury due to CHD [76] and/or due to pulmonary hypoplasia [51].

The lungs of persons with Down syndrome differ in structure and in terms of growth and development. These include enlarged alveolar airspaces, a generalised porous phenotype and subpleural cysts of undetermined significance [77]. Individuals with Down syndrome develop acute lung injury (ALI) at 10 times the rate of those without Down syndrome [14]. Since apoptosis of alveolar epithelial cells is a central feature of ALI [78, 79], it was though that increased apoptotic death would be observed in Down syndrome, but is not [80]. Although respiratory epithelial cells in Down syndrome are imbalanced with regard to free radical scavengers, exposure to oxidative stress does not result in increased apoptosis or inflammation [81]. From autopsy of persons with Down syndrome, it is known that the number of alveoli ranges from 58% to 83% predicted [52]. Such pulmonary hypoplasia is most obvious as small cysts in ∼20–36% of children with Down syndrome [82]. Thus, at some point beyond fetal life, apoptosis of alveolar epithelium may occur in persons with Down syndrome. Individuals with subpleural cysts are asymptomatic. Individuals with Down syndrome as well as mouse models of Down syndrome demonstrate reduced growth and a smaller body size [83]. Primary fibroblasts from individuals with Down syndrome proliferate at rates lower than control cells, and show increased susceptibility to apoptosis and senescence [84–87]. These observations, combined with reduced cerebellar size in Down syndrome [88, 89], suggest that reduced cell number is a general feature of Down syndrome. However, there are no data available that offer a direct comparison of rates of proliferation or apoptosis in lung cells from individuals with Down syndrome compared to controls. Moreover, age-related changes in rates of cell proliferation and/or apoptosis have not been determined in Down syndrome [90]. Thus, it is unclear whether arrested development or precocious ageing impacts respiratory infectious disease in Down syndrome.

Genetic influence of trisomy 21 on pulmonary disease

The Hsa21 gene pre-B-cell leukaemia homeobox-regulating protein-1 (PREP1) encodes a tumour suppressor transcription factor that plays important roles with regard to cell proliferation and epithelial to mesenchymal transition [91]. The p53 protein is a direct target of PREP1, and PREP1 is overexpressed in Down syndrome fibroblasts [92]. PREP1-overexpressing mice are smaller, as cells undergo increased rates of apoptosis due to overactivity of p53 [93]. Although no lung-specific data are available, p53 may also play a role in apoptosis resulting from overexpression of the Hsa21 gene Ets2 transcription factor [94]. Ets2 is a transcription factor and proto-oncogene that controls cell fate, proliferation and apoptosis [95]. Cells in Down syndrome harbour an imbalanced antioxidant defence system associated with high expression of superoxide dismutase 1 (SOD1, Hsa21) [96]. Chronic oxidative stress in Down syndrome fibroblasts is accompanied by p21-dependent replicative senescence [97]. The balance of oxidants/antioxidants greatly affects the biology of the lung and is the subject of intense study [98]; however, there are no lung-specific data available regarding either SOD1 overexpression or antioxidant imbalance in the lungs of persons with Down syndrome. In addition, the Hsa21-encoded micro (mi)RNAs could contribute to hypocellularity. For example, high levels of the miRNA Let-7c induce cell cycle arrest by targeting CDC25a [99]. Similarly, the tumour suppressor activities of Hsa21-encoded miR-99a [100] and miR-125b-2 [101] could contribute to lung hypoplasia. The biology of the lung in Down syndrome can also be affected by overexpression of Hsa21 genes in nonresident cells. For example, lipopolysaccharide-induced ALI in mice is greatly promoted by macrophage expression of miR-155 [102] and miR-155 knockout mice are protected from chronic pulmonary fibrosis after bleomycin exposure [103].

Epigenetic modification of the genome in Down syndrome may also potentially explain dysregulation of lung development and homeostasis. In fibroblasts, the presence of an extra chromosome 21 is associated with hypermethylation of the embryonic organ morphogens HOXB (chromosome 17) and HOXD (chromosome 2) clusters [104]. The hypermethylation is due to upregulation of DNA methyltransferases DNMT3B (chromosome 20) and DNMT3L (Hsa21) and downregulation of demethylases TET2 (chromosome 4) and TET3 (chromosome 2). The epigenetic changes may help explain the existence of chromosomal domains of gene expression dysregulation (GEDDs) [105], and collectively, these data argue for global perturbation of the nuclear chromatin environment in Down syndrome. Intriguingly, the presence of GEDDs is conserved in the Ts65Dn mouse model of Down syndrome [105], even though the chromosomal context is different due to only partial Hsa21 synteny on mouse chromosome 16. In Down syndrome, hypermethylation of morphogenetic genes during development and during post-natal life may help to explain upper airway narrowing and obstruction, lower respiratory tract hypoplasia and inhibition of pulmonary angiogenesis.

With regard to the pulmonary vasculature in Down syndrome, the Hsa21 gene Down syndrome candidate region-1 (DSCR1/regulator of calcineurin (RCAN)-1) is overexpressed and encodes a negative regulator of vascular endothelial growth factor (VEGF)-calcineurin signalling [106, 107]. DYRK1A (Hsa21), also attenuates calcineurin signalling [106], and further angiogenic inhibition in Down syndrome could be provided by overexpression of Hsa21-encoded collagen XVIII, which can be cleaved into endostatin, a potent endogenous angiogenic inhibitor [108]. Non-Hsa21-encoded anti-angiogenesis factors are overexpressed in the fetal lung [53], and while collectively anti-angiogenesis contributes to low rates of solid tumour in Down syndrome [109], it may have negative implications for the pulmonary vasculature. For example, blockade of VEGF receptors in hypoxic rodents causes pulmonary hypertension [110].

Congenital heart defects and cardiovascular disease in Down syndrome

Down syndrome is associated with high incidence (45–50%) of CHD, especially atrioventricular septal defects (AVSD) (table 2) [4, 5]. Surgical correction has greatly decreased mortality in neonates with Down syndrome presenting with AVSD [111]. Uncorrected septal defects lead to shunting of systemic blood to the pulmonary circuit, increased blood flow and PAH, which may persist even after correction. There is an increased incidence of persistent pulmonary hypertension of the newborn (PPHN) in Down syndrome (∼5.2% versus 0.1% in the general population) [59]. The pathophysiology and clinical management of PPHN have recently been reviewed [112]. Progress has been made with regard to biomarkers of paediatric PAH [113, 114], but not PAH in the setting of Down syndrome, (DS-PAH), and there are no animal models specific for DS-PAH. Many factors such as chronic hypoxia, sleep apnoea, recurrent respiratory infection, low birthweight and transient myeloproliferative disease probably contribute to DS-PAH or pulmonary hypertension in Down syndrome [63].

TABLE 2

Congenital heart disease and cardiovascular disease in individuals with Down syndrome

Atherosclerotic disease is the leading cause of death in Europe and worldwide (∼30% of all deaths worldwide) [115]. Death due to CAD is greater among females (51%) than males (42%), and ∼20% of all deaths in Europe are due to coronary heart disease [115]. Morbidity associated with CAD, as measured by hospital discharge rates for CAD, is increasing [115]. Persons with Down syndrome have a low incidence of CAD, particularly atherosclerosis, in spite of increases in obesity and metabolic disturbances in Down syndrome [116]. Smoking is not a major risk factor for CAD in people with Down syndrome [10], and their circulating levels of cholesterol fractions may confer cardioprotection [6]. Atherosclerosis is a complex pathophysiological process involving inflammofibrotic remodelling and occlusion of systemic blood vessels, contributing greatly to the worldwide burden of CAD [117, 118]. Individuals with Down syndrome are resistant to development of atheroma and atherosclerosis [119–121]. A limitation of the earliest studies was that they were conducted using autopsy material from persons with Down syndrome who were institutionalised, where behavioural risks for CAD may have been reduced by control of dietary intake and levels of physical activity. A study found that the intimal media thickness of the carotid artery was lower in individuals with Down syndrome who did not reside in community housing, despite higher C-reactive protein, triglycerides and total body fat [122]. Interestingly, systolic and diastolic blood pressures are lower in Down syndrome subjects compared to controls [122]. In adults with Down syndrome who are aged ≥30 years, hypertension and the use of anti-hypertensive drugs are lower than in the general population [123]. Hypertensive CAD is believed to affect ∼1 billion people worldwide and is a major risk factor for stroke, myocardial infarction and kidney diseases [124]. Persons with Down syndrome may have different autonomic nervous system responses, which can affect cardiovascular function [125, 126].

Children and adults with Down syndrome commonly have hypothyroidism (prevalence ∼25–60%, depending on the study [127–129]). Subclinical hypothyroidism in younger individuals is associated with increased risk of stroke [130]. Thyroid hormone levels are key homeostatic regulators of blood pressure and lipid levels, and have been correlated to heart failure and cardiovascular mortality.

Genetic influence of trisomy 21 on congenital heart disease

CHD in Down syndrome shows a “fixed pattern” of defects, with high numbers of septal defects, but low rates of transposition of the great vessels, tetralogy of Fallot or aortic coarctation [10]. Persons with Down syndrome appear to be protected against CAD despite elevated risk factors. How then does the presence of an extra chromosome 21 contribute to CHD yet protect against CAD? It must be pointed out that Down syndrome is not universally accompanied by CHD; thus, trisomy 21 itself is insufficient to cause CHD. The most recent data suggest that many Hsa21 (i.e. dosage-sensitive) genes are required for development of CHD, but that no single gene may be required [131, 132].

The COL-α1 (VI) and -α2 (VI) chains are encoded by genes located on Hsa21 and their overexpression has been associated with atrioventricular canal defects in Down syndrome [133, 134]. The α3 (VI) chain is encoded by the COL6A3 located at chromosome 2, and individuals with Down syndrome who have single nucleotide polymorphisms in COL6A3 are at increased risk of muscle hypotonia and CHD [135]. Loss-of-function mutations in the cell adhesion molecule cysteine-rich epidermal growth factor-like domain (CRELD)1, encoded on chromosome 3, contribute to CHD in Down syndrome [136]. Increased gene dosage of the Hsa21 gene junctional adhesion molecule (JAM)2 was recently shown to potentiate CHD in mice with CRELD1 mutations [137]. Similarly, haploinsufficiency of the heart morphogen Tbx5 (chromosome 12) results in different left–right cardiac patterning when on a trisomic background in Ts65Dn mice [138]. Collectively, these studies raise the possibility that overdosage of Hsa21 genes combined with perturbed expression of non-Hsa21 genetic modifiers may drive AVSD (and perhaps other developmental morbidities) in Down syndrome [139]. In this regard, many of the deleterious gene variants involving CHD identified to date involve the VEGF-A pathway [140].

As in the lung, Hsa21-encoded microRNAs may play a role in CHD in Down syndrome. In maternal peripheral blood, the plasma expression profile of fetal miR-let-7c and miR-99a are elevated in pregnancies with CHD-positive fetuses [141]. No published data are available evaluating maternal levels of Hsa21-encoded miRs with regard to CHD in Down syndrome. Let-7c controls lineage and stage-specific transcription factors that promote and direct cardiogenesis, while miR-99a has the opposite effects [142]. Thus, a balancing act of the levels of critical Hsa21-encoded miRs and/or proteins, rather than simply Hsa21 gene dosage, may ultimately govern the development of CAD. In another example, Hsa21-encoded PDE9a hydrolyses cGMP and is a major determinant of intracellular cGMP levels important for signalling cascades. PDE9a overexpression contributes to maladaptive hypertrophy and cardiac failure in humans and in a mouse model of aortic stenosis [143]. Conversely, expression of miR-99a correlates closely with cardiac function in mice, and overexpression of miR-99a attenuates both cardiomyocyte hypertrophy in vitro and aortic stenosis-associated cardiac hypertrophy in vivo [144].

As mentioned earlier, rates of CAD in persons with Down syndrome are very low relative to the general population. This is even more surprising given that adults with intellectual disability have higher incidences of cardiac disease, and individuals with Down syndrome commonly have sedentary lifestyles, poor diets, abnormalities in lipid metabolism and obesity [6, 7, 145, 146]. Plasma markers of sterol lipid metabolism (total cholesterol and lipoproteins) in Down syndrome are generally unchanged from age-matched controls and yield few clues into the reduced prevalence of atherosclerotic disease [147]. The question naturally arises: what Hsa21 genes are protective in Down syndrome and are these lower/disturbed in individuals who have CAD within the typical population? Decrease of plasma levels of homocysteine is a therapy that lowers risk of CAD and stroke [148]. Homocysteine is converted to cysteine by enzymatic action of cystionine-β-synthase (Hsa21). Cystionine-β-synthase is overexpressed in Down syndrome [149], and plasma levels of homocysteine are lower [150]. Further research involving persons with Down syndrome could more fully elucidate the mechanisms underlying the “homocysteine theory” of arteriosclerosis [121], a disease affecting a very large number of people worldwide.

The Hsa21-encoded RCAN1 inhibits the calcineurin-nuclear factors of activated T-cells (NFATc) signalling pathway [151]. RCAN1/DSCR1 may have a dual role with regard to the heart in Down syndrome. On one hand, proper developmental regulation of RCAN1 appears to be critical for proper regulation of valvuloseptal development [152]. On the other hand, RCAN1 expression is high in atherosclerotic lesions [153], and experimental inactivation of RCAN1 decreased atherosclerotic lesion burden [154]. This is paradoxical, given that atherosclerosis rates are low in Down syndrome despite overexpression of Hsa21 RCAN1. One clue might come from the suggestion that RCAN1 participates in a positive feedback loop involving inflammation, macrophages and oxidised low-density lipoproteins that potentiates lesion formation and progression [154]. There is evidence for oxidative and nitrosative stress in adults with Down syndrome [155, 156]. Additional clues for how RCAN1 could play a role in the development of atherosclerosis come from the setting of type II diabetes. Cardiovascular disease is the principal cause of death in persons with diabetes (∼382 million people worldwide have diabetes), and reduction of atherosclerotic disease in diabetes is of major clinical importance [157]. RCAN1 is overexpressed in islet cells in type II diabetes without Down syndrome [158]. It is interesting that the Ts65Dn and Ts16 mouse models of Down syndrome are hyperglycaemic and show impaired glucose tolerance [158]. The incidence of type I diabetes is increased in Down syndrome [159], as is type II diabetes [160]. It may be that other overexpressed Hsa21-encoded genes in Down syndrome dampen RCAN1-influenced development of diabetes and atherosclerosis.

Hypertension affects ∼1 billion people worldwide and is a risk factor for stroke and myocardial infarction [124]. The renin–angiotensin–aldosterone system is a hormone system that principally controls blood pressure [161]. Following conversion to angiotensin II from angiotensin I, angiotensin II receptors on blood vessels bind angiotensin II and vasoconstrict, thus increasing blood pressure. Angiotensin receptor blockers (sartans) are in widespread clinical use as antihypertensives [162]. Both females and males with Down syndrome have lower blood pressure than comparison subjects [163], and have lower intima media thickness of coronary arteries [122]. In a study on monozygotic twins discordant for Down syndrome, Hsa21-encoded miR-155 was found to translationally repress one allele of the type-1 angiotensin II receptor gene, resulting in reduced risk of hypertension [164].

Immune system disturbances impacting cardiopulmonary function in Down syndrome

Immune disturbances in Down syndrome account for an enormous and wide-ranging disease burden (table 3), especially pulmonary infectious disease. For persons with Down syndrome aged <3 years, respiratory illnesses are the most common cause of hospital admissions [165], and respiratory disease is by far the most common cause of death in persons with Down syndrome [38]. Both intrinsic immune defects and extrinsic (anatomical) factors contribute to disturbed immune function and respiratory infection in individuals with Down syndrome [166–168]. Reduced numbers of T- and B-lymphocytes and abnormalities of their function both undoubtedly contribute to altered immunoglobulin levels, poor responses to vaccinations and increased respiratory infections [36, 166, 169, 170]. In Down syndrome, the effects of an altered immune system on CHD or CAD are unknown.

TABLE 3

Immune system disturbances in Down syndrome

In Down syndrome, the thymus is smaller than in control subjects and there are fewer mature T-cells expressing the αβ isoform of the T-cell receptor and CD3 [171]. In early childhood, T-lymphocytopenia is present in Down syndrome [172]. Predisposition to infection may continue into adulthood, even as T-lymphocytopenia wanes [172], because the T-lymphocyte phenotype and functional repertoire are abnormal [170]. A higher ratio of T-helper lymphocyte type 1 cells to T-helper lymphocyte type 2 cells and increased interferon-γ production are a feature of Down syndrome [173]. Intriguingly, severe RSV infection is hypothesised to result from disturbance in regulatory T-cell mediated control of host immune function [174].

Studies of B-lymphocytes in the Down syndrome population have revealed a complex portrait. Levels of immunoglobulin classes and responses to vaccination vary in Down syndrome [170]. In one study of 26 children with Down syndrome, only one individual had decreased IgG2 levels, yet 18 out of 26 had increased rates of infection [175, 176]. Following vaccination to influenza A or polysaccharide pneumococcus, antibody responses are active in persons with Down syndrome, yet antibody titres are lower [166, 169, 177, 178]. One possible contribution to increased prevalence and severity of pulmonary infection in Down syndrome could be reduced numbers of subsets of B-cells, such as switched memory B-cells [179, 180]. Deficit of such cells in Down syndrome could result in suboptimal protection from, and response to, infectious agents. Further evidence of B-cell dysfunction includes higher rates of autoimmunity in Down syndrome. In one study, 29% of children with Down syndrome showed positivity to at least one autoantibody, versus 8% in controls [167]. No correlation with infectious disease was investigated. The authors postulated that the presence of autoantibodies in Down syndrome reflected an early immune senescence in Down syndrome. There is currently no evidence that low T-cell (or B-cell) numbers correlate to incidence or severity of lung (or any) infection in Down syndrome [166], but the adaptive immune system in Down syndrome is intrinsically disturbed. Immunophenotyping and enumeration of peripheral blood leukocytes is an important tool to examine the immune system in Down syndrome. Data on resident lung and heart leukocytes are badly needed.

In Down syndrome, innate immune cell analyses show an erythroid cell-skewed developmental abnormality in haematopoiesis in fetal liver and yolk sac [181]. These findings are phenocopied to a large extent in mouse models of Down syndrome [182, 183]. In line with this, transient myeloproliferative disease and macrocytosis are commonly observed in Down syndrome [184]. Unfortunately, the putative role of abnormal numbers and/or function of myeloid-lineage cells in Down syndrome is unknown. Monocytes, macrophages, dendritic cells, neutrophils and natural killer cells play important roles in atherosclerotic plaque formation [185]. Since persons with Down syndrome are protected against atherosclerosis, the study of their innate immunology offers a unique opportunity to compare and contrast the repertoire of innate immune cells to the general population. Such studies may eventually lead to the development of new therapies that would aim to skew myeloid cell subpopulations towards more “atheroprotective” functionality. In the lung, the development and function of myeloid cell subsets is highly complex [186]. Nevertheless, comparative study of Down syndrome and control myeloid cells in the lung should yield insight into differences into the pathobiology of respiratory infection.

Genetic influence of trisomy 21 on immune system disturbances impacting cardiopulmonary function

Altered immunity in Down syndrome may greatly impact cardiopulmonary homeostasis. Several Hsa21-encoded genes may be of special importance in this regard. CD18 integrins are composed of a unique CD11 subunit noncovalently bound to CD18 (β₂ integrin, Hsa21). The role of these integrins is to support key leukocyte adhesive functions critical to antigen presentation, efferocytosis and pathogen clearance [187]. Some reports suggest that CD18 is overexpressed on Down syndrome myeloid cells [188]. However, other studies have not detected any increased CD18 on myeloid cells [189], and the differential findings may be related to whether the cells used had been transformed (lymphoblastoid cells). Due to the importance of CD18 in mediating appropriate leukocyte responses [187], the potential correlation of CD18 expression to gene dosage in Down syndrome should be examined carefully.

The Hsa21 gene Sumo3 was identified in a screen of differentially methylated genes in Down syndrome. Sumo3 was methylated compared to controls, but paradoxically, gene expression for Sumo3 was increased 1.5-fold in accordance with trisomic gene dosage [190]. Sumo3 functions in post-translational sumoylation of proteins regulating immunoglobulin production by B-cells [191] and cytokine production in T-cells [192]. In addition, tight regulation of Sumo proteins has been shown to be critical for cardiac development, cardiac metabolism and cardiac contractility [193]. In another gene methylation screen in Down syndrome, RUNX1 was identified [194]. RUNX1 is a transcription factor that regulates haematopoiesis [195] and is implicated in leukaemia in Down syndrome [196]. In addition, this study highlighted an epigenetic signature in Down syndrome that affects expression of genes involved in cell adhesion molecules, autoimmune thyroid disease, type I diabetes and PI3k-Akt signalling.

Recently, the expression of 20 inflammation-related genes (non-Hsa21) were analysed in peripheral blood obtained from individuals with Down syndrome. Leukocytes from children with Down syndrome expressed less bradykinin receptor B1, which the authors hypothesised might compromise a number of cytokine production pathways and lead to a higher frequency of lung infection [197]. Collectively, the DNA methylation and gene expression studies corroborate the notion that there is a global gene expression change in the genome (Hsa21 and non-Hsa21) [197]. This signature appears to be preserved in inducible pluripotent stem cell (iPSC)-derived progenitors in Down syndrome [181, 198]. Use of iPSCs will be critical tools in the comparative study of developmental and tissue-specific stages in haematopoietic development in Down syndrome and in the typical population.

As mentioned earlier, Down syndrome is associated with increased risk and severity of viral and bacterial pneumonias. RCAN1, encoded on Hsa21, regulates inflammatory responses to Pseudomonas infection both in vitro and in vivo [199]. Interestingly, dysregulation of NFAT, NF-κB and STAT3 signalling pathways was observed in the setting of RCAN1 deficiency. Specifically, although RCAN1 deficiency led to increased bacterial clearance, the mice still died due to systemic inflammation. The authors suggest that overexpression of RCAN1 in Down syndrome may alter downstream effector signalling in pathological ways. In support of this, reduced interleukin-10 and increased STAT3 pathway activation has been reported in Down syndrome [200, 201].

Persons with Down syndrome are prone to develop autoimmune dysfunction. Some aspects of the immmunophenotypic constellation seen in Down syndrome are evocative of autoimmune–polyendocrinopathy–candiasis–ectodermal–dystrophy (APECED), a disease characterised by depressed immune function and autoimmunity. APECED is caused by inactivating mutations in the autoimmune regulator (AIRE) transcription factor gene, which resides on Hsa21 [202]. Decreased AIRE protein expression results in an altered programme of downstream gene expression that compromises myeloid immune cell numbers, phenotypes and function [203]. During development, AIRE controls expression of peripheral tissue specific antigens in medullary thymic epithelial cells through which selection of T-cell clones is accomplished [204]. Autoantibodies and mutations in AIRE have been described in Down syndrome with autoimmune polyendocrine syndrome type I [205], leading to thymic hypofunction and primary immunodeficiency [206]. These studies establish connections between trisomy 21, reduced AIRE and loss of central tolerance. Insufficiency of AIRE may also contribute to the interferonopathy observed in Down syndrome [207], since APECED patients have expanded memory T-cell subsets that produce interferon-γ [202]. AIRE expression has been reported to be decreased in Down syndrome [105].

Conclusions and specific recommendations

With regard to biomedical research and Down syndrome, there is good reason for optimism as we look to the future. However, several limiting factors should be highlighted. We lack solid demographic data with regard to incidence and prevalence of Down syndrome worldwide. Further complicating the study of Down syndrome is the difficulty to ascertain the effect of healthcare systems used by persons with Down syndrome and their families. Individuals with Down syndrome experience similar health conditions and thus use similar services, but they more often experience multiple conditions [22]. We assert that improving the lives of persons with Down syndrome through a renaissance of Hsa21-focused basic and translational research will, in turn, improve the lives of persons without Down syndrome worldwide (figure 2). To reach this goal (faster), we propose the following action points. First, the biomedical research community should increase efforts to reach out to the Down syndrome population and their families to participate in research studies (and vice versa). Second, we need to increase the health-related demographic data available regarding persons with Down syndrome. Third, we should increase funding for basic research focused on cardiopulmonary disease and immunity in Down syndrome, in addition to the important ongoing and future cognitive studies. In the United States, Down syndrome is the most common chromosomal abnormality among live-born infants, yet unfortunately it receives the lowest funding for any genetic condition. Admittedly, the current climate of funding worldwide is extremely challenging. Increased funding is likely to be expedited by increased awareness of the huge impact of cardiopulmonary disease on persons with Down syndrome, and the high potential to leverage research findings to improve the health of all.

FIGURE 2

Research and cardiopulmonary disease in Down syndrome: opportunities for therapeutic leverage. A number of Hsa21-encoded genes affect organ homeostasis. Persons with Down syndrome have low rates of cardiovascular disease (CVD), despite elevated risk factors. In contrast, congenital heart disease (CHD) is highly prevalent in Down syndrome. Pulmonary infectious disease is the leading cause of mortality in Down syndrome, caused by both intrinsic (morphological factors) and extrinsic (immune dysfunction) factors. Listed in each organ cartoon are genes implicated in disturbed heart, lung and immune function. Research into the mechanisms of resistance to development of coronary artery disease and solid tumours inherent in persons with Down syndrome will undoubtedly benefit the larger population (i.e. therapeutic leverage). MI/CAD: myocardial infarction/coronary artery disease; AVSD: atrioventricular septal defect; RSV: respiratory syncytial virus.

Footnotes

• Support statement: This work was supported by a generous seed grant to M.E. Yeager from the Linda Crnic Institute. Funding information for this article has been deposited with the Open Funder Registry.

• Conflict of interest: None declared.

• Provenance: Submitted article, peer reviewed.

• Received September 14, 2016.
• Accepted November 13, 2016.

ERR articles are open access and distributed under the terms of the Creative Commons Attribution Non-Commercial Licence 4.0.

“Down syndrome: an insight of the disease” | Journal of Biomedical Science

Human Chromosome 21

DS complex phenotype results from dosage imbalance of genes located on human chromosome 21(Hsa 21). The genetic nature of DS together with the relatively small size of Hsa 21 encouraged scientist to concentrate efforts towards the complete characterization of this chromosome in the past few years. The length of 21q is 33.5 Mb [11] and 21 p is 5–15 Mb [12]. A total 225 genes was estimated when initial sequence of 21q was published [11]. Hsa 21 has 40.06% repeat content out of which the repeat content of SINE’s, LINE’s, and LTR are 10.84%, 15.15%, 9.21% respectively. The Table 1 given below highlights some of the genes present on chromosome 21.

Table 1
Some common gene present in chromosome 21

Features of DS

There are various conserved features occurring in all DS population, including learning disabilities, craniofacial abnormality and hypotonia in early infancy [13]. Some people of DS are affected by variant phenotypes including atrioventricular septal defects (AVSD) in heart, leukemia’s (both acute megakaryoblastic leukemia(AMKL) and acute lymphoblastic leukemia(ALL)), AD and HD. DS individual have variety of physical characteristics like a small chin, slanted eye, poor muscle tone, a flat nasal bridge, a single crease of the palm and a protuding due to small mouth and large tongue [14]. Other features includes big toe, abnormal pattern of fingerprint and short fingers.

Genetics of the disease

The most common cause of having a DS babies is presence extra copy chromosome 21 resulting in trisomy. The other causes can be Robertsonian translocation and isochromosomal or ring chromosome. Ischromosome is a term used to describe a condition in which two long arms of chromosome separate together rather than the long and short arm separating together during egg sperm development. Trisomy 21 (karyotype 47, XX, + 21 for females and 47, XY, + 21 for males) is caused by a failure of the chromosome 21 to separate during egg or sperm development. In Robertsonian translocation which occurs only in 2-4% of the cases, the long arm of the chromosome 21 is attached to another chromosome (generally chromosome 14). While mosaicism deals with the error or misdivision occurs after fertilization at some point during cell division. Due to this people with mosaic DS have two cell lineages which contribute to tissues and organs of individuals with Mosacism (one with the normal number of chromosomes, and other one with an extra number 21) [15].

Genotype-phenotype correlation

Gene dosage imbalance hypothesis states that DS patients have an increased dosage or copy number of genes on Hsa 21 that may lead to an increase in gene expression [13-15]. This hypothesis has been extended to include the possibility that specific genes or subsets of genes may control specific DS phenotypes [16]. Amplified developmental instability hypothesis states that a non-specific dosage of a number of trisomic genes leads to a genetic imbalance that causes a great impact on the expression and regulation of many genes throughout the genome [13, 14]. Another hypothesis known as critical region hypothesis was also added to this list. Phenotypic analyses was done on individuals with partial trisomy for Hsa21 identified that only one or a few small chromosomal regions, termed “Down syndrome critical regions” (DSCR) a region of 3.8-6.5 Mb on 21q21.22, with approximately 30 genes responsible for the majority of DS phenotypes [15,16]. Previously a region of 1.6 to 2.5 Mb was recognised as sufficient cause for DS pehnotype [17, 18]. The sequencing of Hsa 21 proved to be an important factor in the progression of DS research [19] and led to further insight into genotype-phenotype correlations associated with DS and precise characterizations of DSCR regions [13]. A “critical region” within 21q22 was believed to be responsible for several DS phenotypes including craniofacial abnormalities, congenital heart defects of the endocardial cushions, clinodactyly of the fifth finger and mental retardation [20].

Dual-specificity tyrosine phosphorylation-regulated kinase (DYRK1A) and regulator of calcineurin 1 (RCAN1), Down syndrome cell adhesion molecule (DSCAM) has been suggested to play a critical role in the developing brain and has also been identified as a candidate gene for the increased risk of CHD in DS individuals [21,22]. DSCAM is a critical factor in neural differentiation, axon guidance, and the establishment of neural networks and it has been suggested that the disruption of these processes contributes to the DS neurocognitive phenotype [22]. Based on thorough analyses of studies on humans and DS mouse models, it is evident that there is not a single critical region of genes sufficient to cause all DS phenotypes. Alternatively, it is likely that there are multiple critical regions or critical genes contributing to a respective phenotype or group of phenotypes associated with DS [23].

Various clinical conditions associated to Down syndrome

The various clinical conditions associated with DS are Alzheimer’s disease, heart defects, leukemia, hypertension and gastrointestinal problems (Figure 1). The molecular pathogenesis mechanism of these DS related phenotype must be studied along with its causative agents in order to have a better understanding of the disease. Below are some DS related phenotype discussed in detail which are as follows:

Neurological problems

DS patients have greatly increased risk of early onset AD. After the age of 50, the risk of developing dementia increases in DS patients up to 70% [23-27]. There are various genes reported to cause early onset AD. Some of the genes described in the current literature are APP (amyloid precursor protein), BACE2 (beta secretase 2), PICALM (Phosphatidylinositol binding clathrin assembly protein) and APOE(Apolipoprotein E) etc. APP is an integral membrane protein which is concentrated in synapse of neurons and trisomy of this protein is likely to make significant contribution to the increased frequency of dementia in DS individuals. The triplication of Hsa 21 along with APP in people without DS has been recently shown to be associated with early onset AD. A tetranucleotide repeat, ATTT , in intron 7 of the amyloid precursor protein has been associated with the age of onset of AD in DS in a preliminary study [28]. Various mouse models are used to observe degeneration of basal forebrain cholinergic neurons (BFCNs). Ts65Dn mice is dependent on trisomy of APP expression of retrograde axonal transport [29]. Studies have also revealed that BACE2 which encodes enzyme beta secretase 2 is also involved in AD. APP and BACE 2 genes are located on chromosome 21. The current data on DS support the association of haplotypes in BACE2 with AD [30]. Besides APP and BACE2 genes, other genes like PICALM and APOE are also found to be associated with the age of onset of Alzheimer’s dimentia in DS [31].

Cardiac problems

The incidence of CHD in newborn babies with DS is up to 50% [32]. Endocardial cushion defect also called as atrioventricular cushion defect is most common form which affects up to 40% of the patients. Ventricular septal defect (VSD) is also present in these population which affects up to 35% of the patients [33]. The essential morphological hallmark of an AVSD is the presence of a common atrioventricular junction as compared to the separate right and left atrioventricular junction in the normal heart. Other morphological features include defects of the muscular and membranous atrioventricular septum and an ovoid shape of the common atrioventricular junction. There is disproportion of outlet and inlet dimensions of the left ventricle, with the former greater than the latter as compared to the normal heart where both dimensions are similar [34]. While in case of VSD, the defect lies in ventricular septum of the heart due to which some of the blood from the left ventricle leaks into the right ventric leading to pulmonary hypertension. Mutation in non Hsa 21 CRELD1 (Cysteine rich EGF like domain1) gene contributes to the development of AVSD in DS [35]. CRELD1 is located on chromosome 3p25. It encodes a cell surface protein that functions as cell adhesion molecule and is expressed during cardiac cushion development. CRELD1 gene contains 11 exons spanning approximately 12 kb [36]. To the present, two specific genetic loci for AVSD have been identified. One was AVSD 1 locus present on chromosome 1p31-p21 [37]. Other locus was present on chromosome 3p25 and the corresponding gene was CRELD1 [36,38]. Maslen et al. in [33] have identified two heterozygous missense mutation (p.R329C and p.E414K) with two subjects in DS and AVSD. They have recruited 39 individual of DS with complete AVSD and have found the same mutations. In the same study, DNA of 30 individual of trisomy without CHD was studied for both mutations, no such mutation was identified [35]. R329C which was originally reported in an individual with sporadic partial AVSD and now it is also detected in individual of DS with AVSD. Interestingly, with the same mutation (p.R329C), the severity of heart defect was greater in patients of DS with AVSD. Thus, identification of CRELD 1 mutation in 2/39 individual (5.1%) of DS with complete AVSD suggests the defects in CRELD 1 contribute to pathogenesis of AVSD in context with trisomy 21.

Hematological problems

Patients with DS display a unique spectrum of malignancies, which include leukemia’s as well as solid tumors. The first report of leukemia in a DS patient occurred in 1930 [39] and the first systematic study in 1957 [40]. Studies indicate that patients with DS have a 10–20 fold increased relative risk of leukemia, with a cumulative risk of 2% by age 5 and 2.7% by age 30 [41]. They constitute approximately 2% of all pediatric acute lymphoblastic leukemia(ALL) and approximately 10% of pediatric acute myeloid leukemia (AML). Leukemogenesis of acute megakaryoblastic leukemia (AMKL) in DS patients is associated with the presence of somatic mutations involving GATA 1 gene (or also called as GATA-binding factor 1) [42]. GATA 1 is a chromosome X- linked transcription factor which is essential for erythoid and megakaryocytic differentiation. Because of these GATA 1 mutations, there is a production of shorter GATA 1 protein thereby leading to uncontrolled proliferation of immature megakaryocytes [42,43]. On the other hand, acquired gain of function mutation in Janus Kinase 2 gene are present in approximately 30% of cases with ALL in DS [44,45].

Hypertension

People with DS have been reported to have a reduced incidence of hypertension [46,47]. Trisomy of the Hsa21 microRNA hsa-miR-155 contributes to this [48]. Hsa-miR-155 is proposed to specifically target one allele of the type-1 angiotensin II receptor (AGTR1) gene, resulting in it’s under- expression, which contribute to a reduced risk of hypertension. Further studies are required to validate this hypothesis and determine whether other genes may also protect people with DS against hypertension.

Gastrointestinal problems

DS patients constitute ~12% of all cases of HD. Duodenal stenosis (DST) and imperforate anus (IA) are 260 and 33 times more likely to occur DS [23,49]. HD is a form of low intestinal obstruction caused by the absence of normal myenteric ganglion cells in a segment of the colon [50]. In HD children, the absence of ganglion cells results in the failure of the distal intestine to relax normally. Peristaltic waves do not pass through the aganglionic segment and there is no normal defecation, leading to functional obstruction. Abdominal distention, failure to pass meconium, enterocolitis and bilious vomiting are the predominant signs and symptoms and appear within a few days after birth. Infants with duodenal atresia or DST present with bilious vomiting early in the neonatal period. If left untreated, it will result in severe dehydration and electrolyte imbalance. IA is a birth defects in which the rectum is malformed and it is associated with an increased incidence of some other specific anomalies as well, together being called the VACTERL association: vertebral anomalies, anal atresia, cardiovascular anomalies, tracheoesophageal fistula, esophageal atresia, renal and limb defects.

Alterations of approximately 10 non Hsa21 genes have been linked to this disease [51]. Several researches have shown that HD contain the DSCAM gene which is expressed in neural crest that give rise to enteric nervous system [49]. Overlapping critical region was described both for DST and IA [51]. No other Hsa21 genes have been implicated so far.

Diagnostic methods

Prevention of DS depends upon offering prenatal diagnosis to high risk pregnancies via amniocentesis and chorionic villus sampling (CVS). Amniocentesis and CVS are quite reliable but offers risk of miscarriage of between 0.5 to 1% [52]. Based soft markers like small or no nasal bone, large ventricles and nuchal fold thickness, the risk of DS for fetus can be identified through ultrasound generally at 14 to 24 weeks of gestation [53]. Increased fetal nuchal translucency indicates an increased risk of DS [54]. The other methods used for prenatal diagnosis in which traditional cytogenic analysis is still widely used in different countries. However some rapid molecular assays-FISH(fluorescent in situ hybridization), QF-PCR (quantitative fluorescence PCR), and MLPA(multiplex probe ligation assay)- also used for prenatal diagnosis.

Routine karyotyping

Cytogenetic analysis of metaphase karyotype remains the standard practice to identify not only trisomy 21, but also all other aneuploidies and balanced translocations. Details on diagnostic methods with advantages and disadvantages are mentioned in Table 2.

Table 2
Common techniques used for diagnosis of Down’s syndrome along with its advantages and disadvantages

Rapid aneuploidy testing methods

Over the past 10 years however, several other methods have been developed and used for the rapid detection of trisomy 21, either in fetal life or after birth. The most widely used is FISH of interphase nuclei, using Hsa 21-specific probes or whole-Hsa 21 [55]. An alternative method that is now widely used in some countries is QF-PCR, in which DNA polymorphic markers (microsatellites) on Hsa 21 are used to determine the presence of three different alleles [56]. This method relies on informative markers and the availability of DNA. Rapid diagnosis by PCR-based methods using polymorphic STR markers may reduce these difficulties using conventional approach. Using STR markers method we can detect trisomy in 86.67% cases with only two markers. Using more number of markers can further increase the reliability of the test. Simultaneously parental origin of the nondysjunction can also be detected [57,58]. Additional method to measure copy number of DNA sequences include MLPA [59] which was first introduced in 2002 as a method of relative quantification in DNA. MLPA offers various advantages like – a very short time for diagnosis (2–4 days), effectiveness, simplicity and relatively low costs. It is based on hybridization and PCR method and is divided into four steps: DNA denaturation, hybridization of probe to the complementary target sequence, probe ligation and PCR amplification. And finally capillary electrophoresis of PCR amplified products is carried out. However MLPA is unable to exclude low level placental and true mosaicism [60].

Advancement in the diagnosis

A recent method, termed paralogous sequence quantification (PSQ), uses paralogous sequences to quantify the Hsa 21 copy number. PSQ is a PCR based method for the detection of targeted chromosome number abnormalities termed paralogous sequence quantification (PSQ), based on the use of paralogous genes. Paralogous sequences have a high degree of sequence identity, but accumulate nucleotide substitutions in a locus specific manner. These sequence differences, which are termed as paralogous sequence mismatches (PSMs), can be quantified using pyrosequencing technology, to estimate the relative dosage between different chromosomes. PSQ is a robust, easy to interpret, and easy to set up method for the diagnosis of common aneuploidies, and can be performed in less than 48 h, representing a competitive alternative for widespread use in diagnostic laboratories. The sequencing is quantitatively done by using pyrosequencing [61]. Finally, comparative genomic hybridization (CGH) on BAC chips can be used for the diagnosis of full trisomy or monosomy, and for partial (segmental) aneuploidies [62,63].

Noninvasive Prenatal diagnosis

Fetal cells in maternal ciruculation: Ever since the discovery of presence of fetal lymphocytes in maternal blood was made in 1969, the investigators are trying to develop genetics-based noninvasive prenatal diagnostics (NIPD) [64]. Despite several advantages offered by this approach, the use of fetal cells for NIPD has never reached clinical implementation because of their paucity (on the order of a few cells per milliliter of maternal blood) and concerns of fetal cell persistence in the maternal circulation between pregnancies.

Cell free fetal DNA from maternal serum: This novel approach was proposed in 1997. Cell-free fetal DNA constitutes between 5% and 10% of the total DNA in maternal plasma and increases during gestation and rapidly clears from the circulation post delivery. Several clinical applications based on the analysis of cell-free fetal DNA have been developed like determining fetal Rh D status in Rh D-negative women [65], sex in sex-linked disorders [66,67], and detection of paternally inherited autosomal recessive and dominant mutations [68]. However, there remains the outstanding challenge of the use of cell-free fetal DNA for the detection of chromosomal aneuploidy, in particular trisomies 21, 18, and 13. Several approaches have been adopted like the origin of circulating cell-free fetal DNA is primarily the placenta, whereas maternal cell-free DNA is derived from maternal leukocytes [69]. The approach includes studying differences in genomic DNA methylation between the placenta and paired maternal leukocytes, investigators have characterized placenta-specific epigenetic markers [70] and also finding of circulating cell-free placenta-derived mRNA allowed the identification of placenta-specific mRNA production [71].

The concept of digital PCR was also introduced to serve the same purpose. In digital PCR, individual fetal and maternal circulating cell-free DNA fragments are amplified under limiting-dilution conditions and the total number of chromosome 21 amplifications (representing maternal plus fetal contributions) divided by the number of reference chromosome amplifications should yield a ratio indicating an over- or underrepresentation of chromosome 21.

Although the digital PCR approach is conceptually solid, the low percentage of cell-free fetal DNA in the maternal plasma sample requires the performance of thousands of PCRs to generate a ratio with statistical confidence. This can be overcome by using of multiple target amplifications and enrichment of cell-free fetal DNA which are still under research trail.

Next recent method added to the list is next generation sequencing (NGS) which is based on the principle of clonally amplified DNA templates (or, most recently, single DNA molecules) are sequenced in a massively parallel fashion within a flow cell [72,73]. NGS provides digital quantitative information, in which each sequence read is a countable “sequence tag” representing an individual clonal DNA template or a single DNA molecule. This quantification allows NGS to expand the digital PCR concept of counting cell-free DNA molecules.

Fan et al. and Chiu et al. in 2008 described noninvasive detection of trisomy 21 by NGS [74]. Both groups extracted cell-free DNA from maternal plasma samples from both euploid and trisomy pregnancies. DNA from each sample was sequenced on the Illumina Genome Analyzer, and each sequence read was aligned to the reference human genome. Chiu et al. build on their earlier work with the Illumina Genome Analyzer and demonstrate noninvasive NGS-based trisomy 21 detection with the sequencing-by-ligation approach on the Life Technologies SOLiD platform [75]. Cell-free DNA was extracted from 15 pregnant women, 5 of whom carried trisomy 21 fetuses and it was clonally amplified by emulsion PCR, and sequenced in 1 chamber of an 8-chamber SOLiD slide. This process yielded a median of 59 × 10⁶ 50-base reads per sample. A median of 12 × 10⁶ reads (or 21%) were each aligned uniquely to one location of the reference human genome (with masking of repeat regions), for a coverage of approximately 20% of the haploid human genome. For each trisomy 21 case, the chromosome 21 z score value indicated a 99% chance of a statistically significant difference from the chromosome 21 z scores for the controls. As reported earlier with the Illumina Genome Analyzer, a nonuniform distribution of aligned sequence reads was observed with the SOLiD data.

The current time for sample processing, sequencing, and data interpretation in experienced hands is 5 to 8 days for the Genome Analyzer and SOLiD platforms respectively with the cost of approximately $700 – $1000 per sample. Going forward, one can expect streamlining and automation of technical processes and data analysis, coupled with reduced sequencing costs.

Ultimately, reduced sequencing costs and turnaround times could pave the way for NGS-based NIPD to be considered as an alternative to serum biomarker screening, which,while cost-effective remains prone to false positives. Forty years after the discovery of circulating fetal cells, the vision of NIPD appears clearer and closer.

Management of the disease

One of the hallmarks of DS is the variability in the way that the condition affects people with DS. With the third 21st chromosome existing in every cell, it is not surprising to find that every system in the body is affected in some way. However, not every child with DS has the same problems or associated conditions. Parents of children with DS should be aware of these possible conditions so they can be diagnosed and treated quickly and appropriately. The goal of the study is to point out the most common problems of which parents should be aware.

Timely surgical treatment of cardiac defects during first 6 months of life may prevent from serious complications. Congenital cataracts occur in about 3% of children and must be extracted soon after birth to allow light to reach the retina. A balance diet and regular exercise are needed to maintain appropriate weight. Feeding problems and failure to thrive usually improve after cardiac surgery. A DS child should have regular check up from various consultants. These include:

• Clinical geneticist – Referral to a genetics counseling program is highly desirable

• Developmental pediatrician

• Cardiologist – Early cardiologic evaluation is crucial for diagnosing and treating congenital heart defects, which occur in as many as 60% of these patients

• Pediatric pneumonologist -Recurrent respiratory tract infections are common in patients with DS

• Ophthalmologist

• Neurologist/Neurosurgeon – As many as 10% of patients with DS have epilepsy; therefore, neurologic evaluation may be needed

• Orthopedic specialist

• Child psychiatrist – A child psychiatrist should lead liaison interventions, family therapies, and psychometric evaluations

• Physical and occupational therapist

• Speech-language pathologist

• Audiologist

90,000 What is included in each of the three mandatory screenings during pregnancy and why should they be carried out at strictly defined dates?

Screening during pregnancy is a complex of studies that allows parents and doctors to get the most complete information about the health of an unborn baby. In our country, according to the order of the Ministry of Health of the Russian Federation No. 572n, a planned three-time examination is mandatory during pregnancy. Note that the word “screening” means selection, which means that all women must undergo it, and at a certain stage of pregnancy.The details are explained by the head of the Department of Radiation and Functional Diagnostics, Olesya Strelnikova.

1st screening. The focus is on the assessment of anatomical structures and the risk of developing chromosomal diseases

The study, which includes two medical tests (ultrasound and blood test), is carried out between 10 and 13.6 weeks of pregnancy. At this time, the coccygeal-parietal size (CTE) of the baby is 45-84 mm. If its size is smaller, many indicators subject to research cannot be determined, if larger, they will become uninformative.

During the first ultrasound examination, the doctor assesses the development of the anatomical structures of the fetus. The anatomy of babies who are likely to have a chromosomal disorder is often (but not always) different from the anatomy of healthy fetuses. We identify potential deviations from normal development by special ultrasound markers and allocate these babies to a high risk group for chromosomal diseases.

The first screening is not limited to ultrasound examination only.We take venous blood from a woman for the study of two specific hormones: PAPP-A (plasma protein A) and hCG (human chorionic gonadotropin), produced by the chorionic tissue of the ovum from early pregnancy. Serum levels of these hormones also differ between mothers of healthy babies and mothers carrying babies with probable deviations. For example, low PAPP-A levels can be a sign of chromosomal disorders such as Down syndrome or Edwards syndrome. Note that the level of hormones in the blood of a pregnant woman is influenced by a number of factors: race, her weight, height, the presence of chronic diseases, smoking; pregnancy has occurred naturally or by IVF.

At the DAR center, the calculation of individual risks of fetal chromosomal pathology in the first trimester is carried out in the Astraia program, which was developed by The Fetal Medicine Foundation in London by a group of world-renowned specialists in the field of gynecology and prenatal diagnostics. Today this system is used all over the world and in the first trimester of pregnancy is recognized as the most informative: its accuracy is 95%. The Astraia program employs expert doctors who confirm their competence every year.

An individual card is created for each patient in the program, into which the ultrasound parameters and serum markers are entered, the above indicators (height, weight, etc.) are taken into account. Based on the entered data, Astraia automatically calculates the risk of chromosomal diseases. If it is high, the woman undergoes additional medical genetic counseling.

Thus, during the first screening (which is recognized as the most important), the development of the anatomical structures of the fetus and the probable risk of chromosomal diseases associated with a change in the number or structure of chromosomes are assessed.The examination for the presence of hereditary diseases associated with the breakdown of genes in the chromosomes is carried out after the birth of the baby, during the neonatal screening, the so-called “heel test”. In the Altai Territory, neonatal screening is carried out for 5 hereditary diseases that cannot be diagnosed during pregnancy: congenital hypothyroidism and adrenogenital syndrome, cystic fibrosis, phenylketonuria and galactosemia.

In 2019, 19,132 women underwent the first screening at the DAR center.Of these, 580 pregnant women were selected to be at high risk for chromosomal diseases. They were asked to undergo a more detailed examination to confirm the diagnosis – an invasive prenatal test. The essence of the method is in the collection of fetal material (villi of the placenta or umbilical cord blood) and counting the number of chromosomes. The diagnoses were confirmed in 68. In such cases, the perinatal council of doctors suggests the woman to terminate the pregnancy, since children born with chromosomal diseases, in addition to anatomical defects and impaired vital functions, have a decrease in intelligence and cannot fully adapt in society.But the choice – to carry a pregnancy or terminate – always remains with the woman and her family.

2nd screening. The focus is on the development of anatomical structures and internal organs

The study is carried out from 18 to 21.6 weeks of pregnancy. Such terms are also justified. The fact is that by 22 weeks of pregnancy, the fetus reaches a mass of 500 g, and according to the legislation of the Russian Federation, children who have reached such a mass become citizens of the Russian Federation and receive the rights that already born children have.And if babies are born at a period of 22 weeks or more, they need to provide resuscitation measures and take care of newborns. It is for this reason that the issue of carrying a pregnancy (if gross violations of fetal development are identified) must be resolved before 22 weeks, if there are no other options to change the situation.

The tasks of ultrasound examination of the second screening include the study of not only photometric parameters, but also the anatomical characteristics of vital organs.The kid has already grown up enough to more clearly assess the development of his anatomical structures. So, for example, the heart has become larger: if in the first trimester its diameter is only 6-8 mm, then in the second trimester it is already 18-22. With such sizes, it is easier to assess in detail the anatomy of the heart, to identify gross congenital malformations. The same applies to other organs and systems.

According to order No. 572-n, the second screening is only an ultrasound examination. However, in the Altai Territory, in particular at the DAR center, during the second screening, doctors perform fetal echocardiography – an in-depth examination of the heart.In Russia, this is an optional study, but since congenital heart defects are in the first place among developmental anomalies, the center decided that two doctors should investigate it at once.

So, in 2019, 17 thousand women underwent the second screening at the DAR center. 599 congenital malformations were identified, of which 162 were heart defects (27% of the total number of identified congenital malformations). Among them were both multiple, very difficult, and amenable to correction after birth.

A biochemical study of blood serum of the second trimester is prescribed by a geneticist if the first screening is unsatisfactory or absent, but this test (called “Priska”) has a lower diagnostic value (no more than 75%) in contrast to the first trimester test according to the “Astraia” program. But every woman can perform a complete screening at will, including invasive prenatal diagnosis.

3rd screening. In the area of ​​attention – the exclusion of late manifesting congenital malformations of the fetus

The third screening is done between 30 and 33.6 weeks of gestation.

There are a number of congenital malformations that are commonly called late-onset. These are those fetal diseases that appear only after the 28th week of pregnancy, and, accordingly, can be visualized on ultrasound only in the 3rd trimester. These can be, for example, malformations of the musculoskeletal and urinary systems (the same hydronephrosis or skeletal anomalies manifest themselves only in the 3rd trimester). Some late-onset malformations are due to diseases that the mother suffered during pregnancy.So, valvular heart defects can develop after the expectant mother has suffered ARVI, but after successfully passed the first and second screenings.

Also, during all ultrasound screenings, we assess the location and degree of maturity of the placenta, measure the amniotic index (study of the amount of amniotic fluid). Another component of screening is Doppler vascular examination. Doppler ultrasonography is included in a routine screening study, since it well reflects the state of the uteroplacental and fetal-placental blood flow and allows you to identify various degrees of circulatory disorders.Doppler ultrasonography helps the doctor make sure that the baby is developing normally and is getting enough nutrients and oxygen to do so. With the help of Doppler ultrasound, one can suspect the presence of hypoxia in the fetus, correct the tactics of managing a pregnant woman, and in some cases choose the optimal method of delivery.

In addition, the last screening allows you to detect fetal growth retardation and helps the obstetrician-gynecologist take all the necessary measures in time to successfully complete the pregnancy.

At the DAR center, only pregnant women who are at high risk of developing congenital malformations of the fetus or developing severe obstetric complications undergo the third screening.

In conclusion, we note that only successful cooperation with a doctor will lead you to the long-awaited, safe end of pregnancy.

90,000 March 21 – International Day of Person with Down Syndrome

World Down Syndrome Day (World Down Syndrome Day) has been celebrated annually on March 21 since 2006.

Down syndrome is one of the most common genetic disorders. Each cell in the human body usually contains 46 chromosomes. Chromosomes carry the characteristics that a person inherits from their parents, and they are located in pairs – half from the mother, half from the father. People with Down syndrome have an extra chromosome in the 21st pair, so there are 47 chromosomes in the cells of the body.

Until now, there is no unambiguous opinion about what is the cause of this genetic abnormality.Children with Down syndrome are born with the same frequency in all countries of the world, regardless of wealth or ecology. The appearance of a child with Down syndrome does not depend on the lifestyle, nationality, educational level or social status of the parents. There is no “fault” in the birth of such a child.

Children with Down syndrome lag behind in psychomotor development, there may be (not all!) Various malformations of internal organs. But there are marked individual differences in the success of each child.Such families need help in carrying out correctional classes aimed at the development of the child, when applying to a kindergarten or school. Because only the joint efforts of the family and specialists can change the life of every child for the better.

The diagnosis of Down syndrome can only be made by a geneticist using a blood test showing the presence of an extra chromosome.

Note that various programs are currently being used to detect Down syndrome already during pregnancy.A pregnant woman in the antenatal clinic (at the place of observation) undergoes free ultrasound-screening of the first trimester for a period of 11-13 weeks (measuring the thickness of the collar space, determining the presence of nasal bones), donates blood for biochemical screening (PAPP-A + hCG) and a calculation is performed individual risk for each pregnant woman for Down syndrome, using an automated risk calculation program, adjusted for gestational age, age, body weight, medical history (number of previous births, etc.)).

If a high risk is identified in the medical and genetic consultation of the Presidential Perinatal Center of the Ministry of Health of Chuvashia, on the basis of a numbered referral issued by the antenatal clinic (at the place of observation of a pregnant woman), a clarifying procedure is carried out free of charge – an invasive test (examination of chorionic / placental villi or amniotic fluid) …

In the medical genetic consultation of the Presidential Perinatal Center of the Ministry of Health of Chuvashia (address: Cheboksary, Moskovsky Prospekt, 9 building 1), geneticists are received daily on weekdays by appointment from 08:00 to 18:00, at Saturday – from 08:00 to 13:00 hours, as well as on Open Days.

Make an appointment with a geneticist by calling 8 (8352) 58-05-85 (registry) or using the Unified portal of state services gosuslugi.ru.

You can ask your questions by phone: 8 (8352) 58-05-85.

For reference. The decision to hold International Day of Person with Down Syndrome was made at the initiative of the International (IDSA) and European (EDSA) Down Syndrome Associations at the VI International Symposium on Down Syndrome, which was held in Palma de Mallorca ( Spain).

In December 2011, the UN General Assembly proposed to celebrate this day from 2012 to all states and international organizations in order to raise public awareness of Down syndrome.

The day and month for this event were not chosen by chance – they symbolically reflect the nature of the pathology. March was chosen because Down’s syndrome is a trisomy (March is the third month of the year) on chromosome 21 (therefore March 21).

Down syndrome was first described in 1866 by the British physician John Langdon Down. Almost a hundred years later, in 1959, the French scientist Jerome Lejeune substantiated the genetic origin of this syndrome.

The disease occurs as a result of a genetic abnormality in which an additional chromosome appears in the human body (instead of two chromosomes 21 there are three). As a result, the total number of chromosomes becomes 47 instead of 46.

90,000 Interview: people with autism see the world differently

April 1, 2017

Photo author, iStock

Photo caption,

Autism cannot be cured, but you can adapt to this developmental disability and learn to live with it

Autism – not fully understood disorder.On the eve of World Autism Awareness Day on April 2, we asked our readers to ask us questions about autism that they care about.

People with autism are very different. Some of them have extraordinary abilities and fantastic memory, others have pronounced difficulties with communication and learning.

Clinical psychologist Tatyana Morozova and children’s neurologist Svyatoslav Dovbnya, experts from the Naked Heart Foundation, answer the readers’ questions about the causes of autism and the myths associated with this disorder.Ksenia Gogitidze, a correspondent for the BBC Russian Service, spoke with the experts.

Autism is not a disease

When did medical science identify autism as a disease? Is it a disease?

Autism is not a disease, but a condition or developmental disorder of a biological nature. They cannot get sick and cannot be cured. With this developmental disorder, a person is born, lives and lives to old age.

It is possible to make sure that autism does not interfere with a person’s life, but it cannot be cured of, at least for today.

Due to the fact that their publications were separated by language barriers and boundaries, it has long been thought that there are two different autisms – “Kanner autism” and “Asperger’s syndrome”.

In fact, studies show that there are many “autisms” and people with this disorder are very different. There are people with autism and extraordinary ability, and there are people with severe learning disabilities – all of which are autistic.

Photo author, Science Photo Library

Photo caption,

People with autism process information a little differently, so we can say that they perceive the world differently

Therefore, scientists talk about a whole group of disorders, and all similar conditions are called ” autism spectrum disorders “. (hereinafter – “autism”)

When to diagnose? How do you know if a child has a disorder?

There is no specific test for autism, and the diagnosis is made based on observations of the child’s behavior.

According to the current International Classification of Diseases (ICD-10), autism is not a disease that needs to be treated and can be cured. This is a developmental disorder, a condition that can be corrected with the help of a developmental and educational program.

To understand whether there is any reason to talk about autism in a particular case, one should pay attention to the complex of symptoms known as the “autism triad”.

The main behavioral problems that a child may have and which are directly related to autism are

• communication disorders
• social interaction disorders
• limited, repetitive behaviors, interests and occupations

That is, people with autism have problems with social and emotional skills, they are often unable to conduct a dialogue, they sometimes repeat the same sequence of actions, they do not like changes in the daily routine, they do not know how to pretend and prefer to play alone.

A child with autism sometimes does not use a pointing gesture to show his interest in something, but instead of saying something, repeats the words and phrases he has heard.

It is worth remembering, however, that autism as a rather difficult behavioral diagnosis cannot be made by observing only one parameter: looks / does not look into the eyes, speaks / does not speak.

Photo by Marla Brose / Zuma

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Social inclusion and assistance programs – two main principles

Diagnosis is made only when symptoms affect the life of a child or an adult and prevent him from communicating, learning and developing different skills.

Studies show that it is quite reliably possible to diagnose from the age of one and a half years . The earlier the diagnosis is made, the higher the chance that the child will subsequently be able to adapt to his condition.

What should be called people with autism, and why is it important?

It is considered correct to talk about a person with autism, and not about an “autistic”. In this case, we adhere to the “people first” principle.

Correct terminology is incredibly important to anyone.How we talk about people determines how we relate to them.

More articles from the series “Living with Autism” can be read here.

First of all, we must see a person with his unique characteristics and needs, and only then – his diagnosis. And this helps to remember that people with developmental disabilities have the same rights – to live in a family, study, play, do what they love – like everyone else.

The myth of genius

Is it true that people with autism are geniuses?

This is one of the most common myths about autism.

Again, people with autism are different. Some have outstanding abilities, but there are also those with pronounced learning difficulties. And all of this is autism.

But it is wrong to think that all people with autism are geniuses, although a certain number of people with disabilities do have such abilities.

The point of view, according to which they all have cognitive impairments, is also incorrect.

Autism – a different perspective on the world?

People with autism process information a little differently, so we can say that they perceive the world differently.

For some of them, this allows them to express themselves in art and achieve success in other areas.

At the same time, autism sometimes makes it difficult to understand social situations, intentions and feelings of others. This affects a person’s daily communication and behavior.

What does the world look like through the eyes of a person with autism?

Some adults with autism talk about the peculiarities of their vision of the world: they are more sensitive to certain sounds and smells.

Others notice details that are not particularly important to others.

It is more difficult for them to be in crowded places (train stations, shopping centers, stadiums), however, many come up with strategies for getting out of difficult situations.

Photo author, EyeWire

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Experts unequivocally say that no links have been found between vaccination and autism

How to distinguish a child with autism from a child with developmental delays because the parents did not deal with it?

The first thing to remember is that autism does not arise from insufficient care from parents or other adults caring for the child.The disorder is biological in nature, and most children with autism develop strong attachments to their parents.

Difficulties in children with autism relate to how a person learns, communicates, how the child’s brain processes information. They are most often visible 12 to 18 months after birth.

However, at first glance, distinguishing a child with autism spectrum disorder from a child who lives in a state of severe deprivation (for example, in a child’s home or a social risk family) is sometimes difficult.

Some small children, who have not received proper care, do not initiate contact with people, do not look towards an adult (as if they are disappointed in a relationship), lag behind in the development of speech, are used to calming themselves (swinging, sucking fingers, etc.) show no curiosity.

Experts call such conditions attachment disorders, but now it is clear that the main reason is not a lack of toys, but the absence of a loved one and the frequent change of adults caring for a small child.

Photo author, Getty Images

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Autism is 4 times more common in boys than in girls

In contrast to autism, these symptoms are temporary and gradually disappear when the child is taken care of, for example, transfer of a child from a specialized institution to a foster family.

Is a cure for autism being developed?

There is no magic pill for autism. To date, no country in the world has a drug that can cure autism.

However, there are medications that can help cope with some comorbid conditions, such as regulating mood, controlling hyperactivity, depression and attention deficit disorder.

There are also assistance programs that aim to normalize a person’s life and include him in society. There is no one-size-fits-all support program; it is important to take into account the characteristics and reactions of the child.

Research shows that early intervention programs that involve the whole family lead to good results.

In the USA, for example, 20-30 years ago about 75% of children at the beginning of schooling (by the age of 5) spoke little or did not speak at all. Today, with the emergence of effective assistance programs, only 25% of children do not speak by the age of five.

Photo author, SESAME WORKSHOP

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It is important to change the attitude of society towards people with autism. Sesame Street was recently joined by Julia, who acts like a child with autism

Is it possible completely out of to get rid of autism?

If you start early with your child, you can achieve impressive results.

As recent studies show, a small group of children (about 10%) who received early assistance do not show any further behavioral features that are the basis for the diagnosis of autism.

These are recent findings that require further study.

In most children, the symptoms on the basis of which the diagnosis was made persist throughout their lives, but a program of assistance can correct a person’s behavior and improve his life in society.

About the causes

What are the causes of autism? As a result, there is an increased risk of having a child with autism? Is it possible to somehow reduce the risks of this?

As of today, the cause of autism is still not understood. Research shows that there are risk factors .

• age of parents
• presence of other children with developmental disabilities in the family
• taking certain medications during pregnancy
• prematurity
• autism occurs in boys 4 times more often than girls

that environmental pollution can be considered as one of the risk factors, but so far this is not a fully supported hypothesis by research.

It is also known that some genetic syndromes (X-fragile chromosome, Rett syndrome, Down syndrome) are more likely to have autism.

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Awkward questions: people with disabilities

Can autism develop after receiving mumps vaccine?

The exact cause of autism is still unknown, but the relationship between it and vaccines is perhaps the most well-researched topic.

A huge number of studies carried out in different countries on very large samples of people confidently show the absence of any connection between vaccination and autism .

No association was found between the type of vaccination, the age at which the vaccine was administered, the number of vaccines and autism.

What is the reason for the increase in the number of children with autism?

Photo by, iStock

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Feeding independent of autism

People around the world are trying to understand why there is an increase in the number of people with autism spectrum disorders.

One of the explanations is improved diagnostics (clearer criteria for making a diagnosis, revision of previously made diagnoses).

This may partly explain the increase in the number of diagnoses. Studies are underway to determine risk factors for autism depending on environmental factors, but so far no definitive data have been obtained.

About social adaptation

How to adapt a person with autism to professional life?

Profession success often depends on social skills that are not well developed in people with autism.Therefore, they need professional support and assistance, especially at the beginning of work.

People with autism can be great workers. Their characteristics – attention to detail, dedication, discipline – can be an advantage in a work that requires a high concentration of attention.

How to communicate with a child with autism in the company of friends, is it necessary to be active, ask questions, involve in the game? How to communicate with a child to strangers? What can and cannot be done?

There are special programs to help a child with autism develop social skills, communication and play with peers.

He is taught to enter into a dialogue and maintain it, to adhere to the rules in the game, to refuse what is unpleasant.

Programs also provide training for people who surround the child – both children and adults.

It is very important to give a child with disabilities time to process information, not to rush him, to support the initiative. It is better to avoid long sentences and phraseological units.

Is it possible for children with autism to attend mainstream schools?

Many children with autism are enrolled in mainstream schools according to the most common curricula.

Some need only minor adaptations of the school curriculum, for example, the ability to respond in writing if verbal response is difficult.

Photo author, iStock

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The sooner you start a program to help children with autism, the better the results

Today, experts in the field of child development unanimously say that for a normal life for a child with special needs, he needs to communicate with ordinary peers and learn with them.

The inclusive education level may vary. For example, children with autism, combined with learning difficulties, can study certain subjects in a special class, and in other subjects (physical education, music, favorite subjects, disciplines that are easier to learn) be among their ordinary peers.

It is very important that the children are together during recess, in the cafeteria, see each other and get used to it.

After all, after leaving school, a child with disabilities will live among ordinary people, and not in a specially organized group.

Photo author, Science Photo Library

Photo caption,

Difficulties associated with autism are most often noticeable in a child after the age of 12-18 months.

Is autism inherited?

Autism is genetic in nature, but the exact cause of the disorder is not yet known.

Studies show that the likelihood that a family with a developmental disability will have a child with a disorder is higher.But this is not a clear correlation, but just a slight increase in risk.

Genetic counseling in family planning can help identify the risk of many genetic syndromes, but in the case of autism, no specific recommendations can be made yet.

If no associated genetic conditions are found, the likelihood of having a typically developing child is higher than the risk of having a child with autism.

Disclaimer

All information contained in this article is for general information only and should not be construed as a substitute for the medical advice of your healthcare professional or any other healthcare professional.The BBC is not responsible and cannot be held responsible for the content of external Internet sites mentioned in this material. It also does not call for the use of any commercial products or services mentioned or recommended on any of these sites. Always contact your healthcare professional if you have any concerns about your health.

Lifetime quarantine. Why adults with Down syndrome have no chance of a job in Ukraine

When a person with Down syndrome (DM) or another form of mental disability reaches adulthood, inclusion no longer covers them.School, socialization and separate circles for children with disabilities are left behind, and adulthood never begins. In Ukraine, adults with SD have almost no chance of finding a job, so they return to apartments, where, if they are lucky, they do housework until the end of their lives. In the worst case, they end up in closed boarding schools when the guardians die.

Zaborona journalist Alena Vishnitskaya explains why adults with Down syndrome have almost no chance of starting an independent adult life – although some are ready for it.

Work from mother

At nineteen, Valentin, unlike about 15 thousand other adults with Down syndrome in Ukraine, is employed. Together with a friend, he works as a waiter and barista in the Lutsk cafe “Old Town”. He brews coffee, knocks down the cream, wipes the dishes, accepts and takes out orders, makes sure that the tables are clean and the guests leave happy. Valentine has a job because his mom invented it.

Larisa gave birth to Valentine at twenty.This was her first child – and she absolutely did not understand what to do with him. There was no Internet, as well as available information, where to run, how to treat, and how to live in general.

Photo from Larisa’s Facebook page

Down syndrome is a genetic pathology. Of all chromosomal abnormalities, it happens most often, only in one case out of a hundred is heredity. Most people with diabetes have mild to moderate intellectual disabilities, so they can go to school with other children, play sports and arts successfully, and then take care of themselves, including cooking, cleaning, and self-driving.In addition to physical features, people with Down syndrome often have concomitant health problems: defects of the heart, vision, hearing, digestive system, and speech. They are different for every child.

A child with Down syndrome is born in about every seven hundredth family – this is not influenced by the era, or the way or conditions of life, or the continent, or the climate, or any other factors. Roulette. Larissa became this seven hundredth. When Valentin was several years old, she realized that she needed to put the child on her own feet, socialize, teach and introduce the world.She joined a public organization and began to deal with children with diabetes in Lutsk – she organized circles, prescribed programs, looked for partners, explained to others what Down syndrome is.

When Valentin was fifteen and was finishing ninth grade, she initiated the “One Day at Work” project. The idea was to give children the opportunity to try themselves in different professions, like working in a library or packing toys in a factory. She did not even dream that her child would work in a real job – then, in 2017, there were no such precedents in Ukraine yet, says Larisa.For several weeks, Larisa and other mothers agreed with the business owners – they say, let the child go to some of the processes, he will, under supervision and after instructions, try himself in real work. One day at work was preceded by weeks of agreements, communication with staff, explanations of how to interact and respond to “others”.

Photo from Larisa’s Facebook page

Larisa found a day job for almost all the children whose parents agreed to it. Except for his own son.More precisely, I found it for him last and almost by accident.

“The roller at home was very fond of making coffee. We walked around the city – and went in the center to a cafe-confectionery, the owner of which was a young girl, Yulia. I then asked her – really, that a person with Down syndrome should work next to her staff. She replied – well, yes, of course, but I don’t know how to work with them. Then we began to discuss all the risks, conditions, nuances, and Valik went to his first working day, “- recalls Larisa.

The agreement on one working day grew into a whole summer – the owner of the cafe did not mind, and Valentin woke up earlier every morning to put on a uniform in advance, come to work and make coffee for people. It seems that only Larisa was worried: “I was worried whether he would do everything right, whether there would be complaints. What if he breaks something? What if people don’t understand him? The owner then said to me: “So what if it breaks? We, too, can break something. Why should I pay attention to the fact that it is Valentin who can do it? ”- recalls Larisa.

In the fall, the next school year began, the guy went to the tenth grade, then to the eleventh. And then I graduated from school.

“Up to the age of 18, the child is still covered by inclusion in schools and kindergartens, he goes to some classes, socializes. And when he finishes school, he returns to the four walls of his room, because he does not have the opportunity to be realized, ”explains Larisa. She understood that this was the end of the state’s participation in the life of her child. Among her acquaintances, the parents of children with the syndrome, most of them worked, so they could not look after adult children around the clock.Some went to work, and the child was locked in the apartment until evening. Even if he was 35 years old.

“The quarantine began, and everyone was afraid that they were locked up within four walls. And people with Down syndrome live like this all the time, ”says the woman. Larisa understood that Valentine’s adult life is exclusively her business.

This winter, together with another mother of a child with DM, Elena, Larisa opened a cafe – the first institution in Lutsk, where people with Down syndrome began to work.There used to be an ATO cafe on this place – the military opened a business after they returned from the East: “But in the end they decided to close the business. Probably, we found ourselves in something else, retired – and we took the risk of adopting ”.

Photo from Larisa’s Facebook page

Most of all, Larisa was not afraid of business, in which she did not understand anything. First of all, she was afraid of how society would perceive this initiative – according to her plan, people with the syndrome should not only work in a cafe, but also be visible and communicate with visitors.It was not clear how people would react to “others”. There were no similar projects in Lutsk. And those that were in other cities were not always encouraging. Recently in Kharkiv, local residents opposed the Snow on the Head cafe, where people with Down syndrome work. The neighbors were against the installation of a ramp – they say, they do not want to see people in wheelchairs in their yard. And about the workers themselves with the syndrome, they said that they, they say, can pounce – “who knows what is in their head.” The coffee shop continues to operate, but this case shows that mental characteristics in Ukraine are still very stigmatized.

Fears began to dissipate, as soon as the café earned money, the Kharkiv scenario in Lutsk did not materialize. The guys learned how to use the coffee machine in a few days, there were no conflicts with visitors, everyone was happy with each other. Now two guys with the syndrome work in the cafe, but from time to time their friends come to help – then they all sit down at a large table and put hundreds of napkins for guests. Larisa and Elena plan to expand the team as soon as they get on their feet.In Lutsk, it is now the only place where people with mental disabilities can work.

“We want people to come to us not out of pity, but for delicious coffee. And I want not to be afraid that society will hook the more vulnerable. Parents of such children often feel discouraged because they are afraid to experience pain every time when they look at their child askance or react in a special way to what a child without the syndrome can do, ”says Larisa.

Foreign business

More than 15 thousand people live in Ukraine.adults with Down syndrome, explains Ivanna Vikhtinskaya, coordinator of the employment support project at Down Syndrome. There will not be even half a percent of cases when such people work – we are talking about rare, isolated stories, such as a coffee shop in Lutsk, a cafe in Kharkov, a bakery in Kiev, or about several people who work in supermarkets and put goods on the shelves. …

Photo from Larisa’s Facebook page

The state declares the protection of the rights of persons with disabilities – in particular, their right to work.A third of more than 2 million people are officially employed. However, this employment exists mainly on paper – as of 2016, experts call the real figure 13%. According to the law, at least one person with a disability must work in enterprises with a staff of 8 to 25 people. And if the enterprise is larger, then such should be about 4%. If there are no people with disabilities in the state, the company is obliged to pay a fine. Therefore, enterprises often formalize people with disabilities to avoid sanctions, but do not give them jobs.

This figure is relevant for all people with disabilities. As far as the mental one is concerned, everything is even more complicated here. People, particularly those with Down syndrome, need a companion at work. In addition, Ivanna explains, colleagues must receive training to understand how to effectively interact with people with diabetes. All this falls on the shoulders of employers, because there are no corresponding government programs.

“When companies do this, they independently form their socially responsible person, spending their own time and resources,” says Ivanna.The Down Syndrome organization, in particular, communicates with companies that are ready to hire a person with the syndrome, but do not know where to start. During the employment project, Ivanna Vikhtinskaya and her colleagues managed to arrange six adults in the AUCHAN hypermarket chain.

Photo from Larisa’s Facebook page

In the world, people with Down syndrome can work, for example, in the service sector, in supermarkets, sort or pack goods, work in hotels, cafes, and perform landscape work.In general, the scope is as wide as possible – Down syndrome has various manifestations, therefore, needs and opportunities for implementation should be different. But the scenario in Ukrainian reality is mostly the same – upon reaching the age of majority, inclusion ceases to embrace children: “If there is a country house, then a person can help parents in the fresh air. If the apartment – then it remains closed within four walls. The life of an adult does not come after the age of majority, ”explains Ivanna.

In addition, there are legal obstacles.People with Down syndrome are usually given a first and second form of disability, which states that they are “disabled”.

“The Commission writes this without hesitation. Doctors see a person with a mental disability in front of them – and they think: well, where will he work? After that, they indicate that it is inoperable, or simply put a dash. This generally makes further work impossible, ”explains Ivanna. It is theoretically possible to reconsider the decision, but it takes a lot of time, persistence and effort – to pass the commission completely, you need to spend at least six months.

It is possible to regulate such approaches only in manual mode – when, during the commission, parents or guardians clearly articulate that they would like their child to have the opportunity to be realized, and when a person with the syndrome “shows his skills”. But none of this makes sense if the commission is unlucky.

“It is only the human factor that is decisive – who you fall into. There is no green light for everyone. If you are lucky, they will write in the conclusion “it can work in specially created conditions,” says the expert.

Photo from Larisa’s Facebook page

We are not talking about the employment of all people with diabetes – even in the developed countries of the world, in particular in the EU, up to 10-15% of all adults with the syndrome are settled in the free labor market, explains Ivanna: “Why? There are nuances in development, different levels of skill, different training. But this does not mean that other people are sitting closed within four walls. ”

For the remaining 85–90%, alternative forms of employment are provided – more secure ones. For example, it might be a center where adults with the syndrome come during the day, socialize, and can do certain tasks such as folding boxes.It works like this: the company outsource work, the local community is involved, and some functions are delegated to people with mental disabilities. In any case, in order for such people to work, special conditions must be created for them: a shorter working day, understandable functions that they can perform.

Employers also need help – they must understand how to organize production, how to find a common language, where to look for assistants. In order for people with diabetes to be able to work in real jobs in the future, it is necessary to change the system comprehensively: improve the quality of special education, provide institutions with assistants, and subsidize employers.Experts have repeatedly called on the ministries to make a number of decisions necessary for this, but they have not yet received noticeable results.

Zaborona sent a request to the Ministry of Social Policy and asked what opportunities adults with mental disabilities have for work in Ukraine. Waiting for an answer.

90,000 Childbirth at 40+: doctor about late childbirth

Obstetrician gynecologist of the highest category Pilipenko Lyudmila Nikolaevna told about the risks of late motherhood and modern methods of preventing them

Childbirth at 40+ is in trend today

Modern women give birth later and later: no one will surprise anyone with their first pregnancy after forty years.But forty – enough examples of successful childbirth even after fifty years. There are many reasons for this reproductive behavior, and they are usually complex. This can be economic, psychological, or any other reasons. But – most importantly – the level of modern medicine and new reproductive technologies make late motherhood physically possible.

And indeed, in recent years, childbirth at the age of 40 is no longer surprising, it has become quite commonplace.

Moreover, in many developed countries of the world, in particular in the UK and the USA, the number of women who gave birth after 40 already exceeds the number of those who became a mother before the age of 20.

The development of reproductive technologies and advances in medicine shifts the female age of childbearing further and further. Bridget Nielsen gave birth at 54, Janet Jackson at 50, Halle Berry at 47, Rachel Weisz at 48.

Since pregnancy and childbirth place an enormous burden on all organs and systems of the mother’s body, the question arises: how safe is very late motherhood for a woman and for a child?

In women over 40, the incidence of complications of pregnancy and childbirth is significantly higher than in those who give birth at a younger age.

If you decide to postpone motherhood after 40, be prepared for the fact that pregnancy and childbirth can be associated with high risks.

The decision to give birth after 40 certainly needs to be approached with even greater awareness than pregnancy at a young age.

On one side of the balance – a new page in life and a lot of positive emotions, and on the other – a high risk of chromosomal abnormalities in a child.

From the point of view of nature, everything is pretty straightforward: it is better to give birth to children from 23 to 35 years old.

Because the quality of eggs is better in young women, the likelihood of chromosomal abnormalities in the fetus is less, they themselves still have a lot of strength and health in order not only to successfully carry and give birth to a baby, but also to get up to him at night in the early years. Starting at the age of thirty-five, a countdown begins, one might say, and a woman’s fertility is slowly falling, and the risks are becoming more and more.

A woman who has decided to give birth after forty years needs to understand the peculiarities of such a pregnancy and try to reduce these risks in all possible ways.

Increased risk of fetal abnormalities

Beginning at the age of 35, and especially after 40, the likelihood of a chromosomal abnormality in a child increases. These can be both relatively common pathologies such as Down syndrome, Patau or Edwards syndrome, or more rare. Take Down syndrome as the most common and compatible with life. So, if a 30-year-old mother has about one in 800 chances of having a baby with Down syndrome, then by the age of 40 it is already a ratio of one to a hundred, and at 44 years old – one in 25.

Therefore, all these categorical statements “What, did you get pregnant at the age of 40? You will have a baby with Down syndrome! ” are far from the truth. Yes, the risk is increasing, but the probability is still not critical.

In addition, there are modern, highly accurate and safe methods for testing the fetus for genetic abnormalities. For example, a non-invasive prenatal test is performed, that is, a test on the mother’s blood, starting from 10-11 weeks of pregnancy. DNA of the fetus is isolated from the mother’s blood and they look to see if there are genetic abnormalities – both frequent and quite rare.

Of course, there are more traditional and also quite accurate research methods, but they are associated with a risk to the fetus, because the tissues that are previously removed from the uterine cavity are tested.

There are also screenings that are carried out in the first and second trimester in antenatal clinics for blood and ultrasound. Their accuracy is quite low, and if you fundamentally know about the presence or absence of a chromosomal abnormality in the fetus, then it is advisable to use more accurate methods.

50% of late pregnancies are terminated before 12 weeks

Also, in parallel with the increase in the likelihood of pathologies, the frequency of early abortions is also increasing, that is, these are interrelated things. Half of all late pregnancies are terminated before twelve weeks. Accordingly, it will be either a frozen pregnancy or a miscarriage.

Caesarean treatment will help to avoid intrauterine fetal death

In addition to genetic defects in the embryo and early termination of pregnancy, women in the older age group may experience a number of other problems related specifically to age and health.It can be a whole baggage of gynecological diseases, some kind of surgery, uterine fibroids that arose at the age of 38-40 years. And all this can have an impact on the course of pregnancy, on the risks of bleeding during childbirth, even on the birth itself.

It is reliably known that in pregnant women over 39 years of age, it is advisable not to wait forty weeks, but to give birth earlier.

Because, starting from the thirty-ninth week, the percentage of intrauterine fetal death increases: the placenta works under a heavy load, the body has practically spent all its energy on pregnancy.In a normal situation, the body realizes that its resources are not enough, and labor begins.

In older patients, the “time to go” mechanism may not start, and the fetus simply dies in utero. And this is a normal child, with a normal set of chromosomes, just the placenta in the last stages can no longer cope with its function, and the “lever” at the beginning of labor does not work. Therefore, doctors recommend such women to have a caesarean section for a period of 38-39 weeks.

The main thing is a healthy lifestyle

In general, the outcome of pregnancy and childbirth depends on how healthy the woman is.At forty, the body can survive in different ways for different people. The place of residence of the family plays a significant role: it is one thing when a woman lives in nature, eats natural products, moves enough, and quite another, when she lives in a metropolis, eats food from the nearest supermarket, is not much outdoors, but sits a lot at the monitor and is nervous.

But this does not mean that if your health is not very good, you should not dream of a child. Even in the most difficult cases, healthy children are obtained, although such pregnancies are, of course, more difficult to maintain.Several specialists are engaged in this in our medical center at once: an endocrinologist, a therapist, a gynecologist. We live in an iodine-deficient territory, and the longer we live in it, the more chances that thyroid disorders will accumulate, hypothyroidism, for example.

You should regularly undergo preventive medical examinations.

Do not think that when you are 40 years old, that’s it, you can’t give birth.

When deciding to give birth at a later age, a woman needs to undergo a complete examination.That is, not only to see the reproductive system, but also to check the heart, blood vessels, hormones, and so on. It is equally important to start (at least start!) To lead a healthy lifestyle: quit bad habits, start eating right and love physical activity.

Our medical center “Avicenna” has been successfully specializing in the treatment of infertility and miscarriage for more than 11 years, as well as in preparing women for pregnancy and further pregnancy management.

Obstetricians – gynecologists together with urologist – andrologist and narrow specialists solve numerous problems of future parents so that a healthy long-awaited baby is born.

An integrated approach and highly effective techniques are used to prepare for pregnancy. For examination of men: MAP test, electron microscopy of spermatozoa. The latest diagnostic and therapeutic technologies are used: laboratory diagnostics, ultrasound diagnostics, functional diagnostics, physiotherapy, hirudotherapy, plasma therapy, carboxytherapy, kinesiotaping, reflexology, manual therapy.

Remember: nothing is impossible and over 40 is not a sentence! There are only three steps separating you from the opportunity to become happy parents:

– tune in;

– contact the specialists of our clinic;

– to receive the necessary qualified assistance.

The specialists of the MC “Avicenna” recommend that both partners come to the doctor’s appointment – for more effective preparation for the desired pregnancy. “

Sign up for a consultation with an obstetrician-gynecologist of the highest category Pylypenko Lyudmila Nikolaevna by phone 8 (3452) 59-39-57 or through the online registration system on the website

MBOU Center for psychological, pedagogical, medical and social assistance “Support”

March 21 – International Down Syndrome Day.We are participating in a flash mob to support these people. Different socks are a symbol of dissimilarity. People with Down syndrome have their own characteristics. But is it only with them?

March 21st is the World Down Syndrome Day. This date entered the calendar in 2005. The initiative belonged to the participants in the 6th symposium dedicated to this topic. In Russia, the Day of a Person with Down Syndrome was first celebrated in 2011. In the same year, the UN General Assembly declared March 21 World Down Syndrome Day (Resolution No. A / RES / 66/149).

The General Assembly decided that this Day would be celebrated on March 21 every year starting in 2012 and invited all Member States, relevant UN organizations and other international organizations, as well as civil society, including non-governmental organizations and the private sector, to celebrate World Day appropriately people with Down syndrome in order to raise public awareness of the disease.

Down syndrome is a form of naturally developing congenital genomic abnormality that is common in all regions of the world and often leads to changes in motor skills, physical characteristics and health.Adequate access to health care, early intervention programs and inclusive education and research are vital to the growth and development of patients.

The estimated incidence of Down syndrome ranges from 1 in 1000 to 1 in 1100 live births worldwide. Every year, approximately 3,000 to 5,000 babies are born with this chromosomal disorder.

The very date of March 21 was not chosen by chance – this is a symbolic designation of the Down syndrome itself, the cause of which is the trisomy of one of the chromosomes: in a person suffering from this disease, the 21st chromosome is present in three copies.Translated into the “language of the calendar”, it turned out to be the 21st day of the third month.

The English physician John Langdon Down (1828-1896) in 1862 was the first to describe the syndrome, which later received his name, as a form of mental illness. The connection between the origin of the congenital syndrome and the number of chromosomes was revealed in 1959 by the French geneticist Jérôme Lejeune (1926-1994).

Interestingly, the discoverer of the syndrome called it “Mongolism.” This term arose due to the fact that the face of a person suffering from Down syndrome resembles the face of a representative of the Mongoloid race.However, the World Health Organization canceled this name in 1965 after the appeal of specialists from Mongolia.

Perhaps the current name of the syndrome will be changed to something else. The US National Institutes of Health has already recommended eliminating the possessive form in the name of the syndrome, arguing that Dr. Down himself did not suffer from this disorder.

Down syndrome is characterized by a certain set of physiological features, such as a “flat face”, a skin fold on the neck, joint hypermobility, muscle hypotension and some others.And most importantly, a child with such a disorder develops noticeably more slowly than his peers.

Despite the widespread belief that these children are not capable of learning, they may well master both self-care skills and more complex actions . There is even the only theater in the world in Moscow where all people have Down syndrome. The troupe, which is called “The Innocent”, successfully tours and gathers full houses.

The quality of life of people with Down syndrome can be improved by meeting their medical needs, which include: regular check-ups with health workers to monitor psychophysical development and ensure timely intervention, be it physical therapy, counseling or special education.Down syndrome patients can achieve an optimal quality of life through parenting and support, medical advice, and community support systems such as special schools. This facilitates their participation in public life and the development of their personal potential.

Source: https://www.calend.ru/holidays/0/0/2972/

Events archive

90,000 Pain in the lower abdomen and lower back

Pain in the lower abdomen and lower back – a phenomenon that worries more than a dozen people.However, unfortunately, many people prefer to pretend that they do not exist, or to think that they will pass and will not be repeated. The maximum that many patients do is to muffle pain in the lower abdomen and lower back with painkillers. For a while, this, of course, has its effect, but it does not eliminate the cause of pain in the lower abdomen and lower back. Therefore, if the pains in the lower abdomen and lower back recur again and again, you must definitely consult a doctor.

Very often there is a combination of pulling pains in the lower abdomen with lower back pain.More often this phenomenon occurs in women, but pains in the lower abdomen and lower back and in representatives of the male part of humanity are not uncommon.

Cause of pain in the lower abdomen and lower back

Acute cystitis is a common and most common cause of pain in the lower abdomen and lower back. In this case, the presence of blood during urination, painful sensations at the end of urination, and frequent urge to “go to the toilet” are added to the pains in the lower abdomen and lower back. Such symptoms indicate cystitis; for an accurate diagnosis, it is necessary to undergo a number of additional examinations by a urologist.

In the event that the above symptoms of cystitis are not observed, then perhaps the patient is dealing with intestinal problems. Pain in the lower abdomen and lower back in a woman may also indicate an ovarian cyst in the initial stages, adnexitis, or some other fairly serious diseases associated with the female genitourinary system. Most accurately, the cause of pain in the lower abdomen and lower back in a woman can be determined by a gynecologist.

As for pain in the lower abdomen and lower back in men, this is a rather rare occurrence.But these symptoms may indicate that the digestive or genitourinary system is not working as it should. Lower abdominal pain and lower back pain can also accompany prostatitis. If pains of this nature are found, a man should contact a gastroenterologist and urologist.

If pain in the lower abdomen and lower back is accompanied by an increase in temperature, then diseases such as mycoplasmosis, chlamydia, gonorrhea, ureaplasmosis are possible.

Symptoms of pain in the lower abdomen and lower back

Pain in the lower abdomen and lower back can be sharp or aching, cramping.Also, along with them, you can often observe an increase or decrease in temperature, vomiting, bleeding, nausea, chills, blood when urinating, frequent urge to urinate.

The lower abdomen hurts and pulls the lower back

If the lower abdomen hurts and pulls the lower back – this phenomenon in medical practice is called chronic pelvic pain. If the above symptoms are observed in a patient within six months, doctors make this diagnosis. In most cases, chronic pain in the lower abdomen and lower back causes gynecological diseases, and relatively rarely – extragenital.

More rare causes of pain in the lower abdomen and lower back may be the presence of:

• osteochondrosis of the spine;
• herniated disc;
• arthrosis of the intervertebral joints;
• rheumatoid arthritis;
• stenosis of the intervertebral canal;
• infectious lesions of the vertebrae;
• scoliosis;
• stroke;
• osteoporosis.

Abdominal and lower back pain in young girls

Pain in the abdomen and lower back most often occurs before menstruation or on the days of “menstruation”. Menstrual cramps are often palpable during the first three days. More than half of women on Earth suffer from menstrual cramps, although most note that their character is moderate, the intensity is low, therefore they can be easily tolerated.

Specialists say that menstrual pain is influenced by special hormones called prostaglandins.But the pains can be very intense and excruciating. They can also be caused by other complicating factors, such as endometriosis or fibroma.

Pain in the lower abdomen and lower back in pregnant women

Pain in the lower abdomen and lower back in pregnant women is quite common. During pregnancy, the spine is under increased stress. If the pulling pain began to manifest itself already immediately before childbirth, these may be false contractions (Braxton-Hicks). The presence of such symptoms in the early stages is dangerous, they can threaten a miscarriage.Then, as soon as possible, you need to report the situation to the doctors.

Pain in the lower abdomen and lower back in girls can also be a signal of hypothermia. The bare lower back, which girls often leave open for the sake of beauty, can become hypothermic and, worst of all, lead to infertility.

What to do if lower abdomen and lower back hurts

When a doctor diagnoses a patient in order to identify the cause of pain in the lower abdomen and lower back, then first of all he needs to understand the degree of pain intensity and their nature.In women, it is important to establish whether there is a connection with pregnancy or menstruation.

For diagnosis, it is important to establish the nature of pain and the frequency of its occurrence, since different characteristics may indicate different diseases. If the nature of the course of the disease is acute, then the patient can observe the presence of cramping pains, which gradually increase, complications bring chills, nausea, and increased body temperature. Such pains indicate that the inflammatory process is rapidly developing.When pain of this nature has been observed for a long time, some kind of chronic disease may well develop, therefore it is imperative and as soon as possible to go to the doctor’s office.

Clinical laboratory and apparatus-instrumental research methods are used to diagnose pain in the lower abdomen and lower back:

• laboratory tests for herpes infection that affects the development of pelvic ganglioneuritis;
• ultrasound examination of the pelvic organs (ultrasound) – to exclude organic diseases of the genitourinary system;
• X-ray of the spine and pelvic bones;
• absorption densitometry to rule out osteoporosis;
• radiological examinations (irrigoscopy), endoscopic (sigmoidoscopy, colonoscopy, cystoscopy) of the gastrointestinal tract and bladder;
• laparoscopy.

Treatment of pain in the lower abdomen and lower back

To eliminate pain in the lower abdomen and lower back, doctors do not recommend taking painkillers on their own. This can only worsen the patient’s condition. First you need to understand what exactly caused pulling, stabbing, aching or sharp pains in the lower abdomen and lower back, therefore independent initiatives are undesirable here. Pain is, first of all, a signal from the body that some kind of disease has arisen and is developing, which needs treatment only after a specific cause has been established, and only a doctor can do this.As we have already found out, the range of causes is very wide, and it is not an option to drown out pain in the lower abdomen and lower back with the help of pain relievers, since the symptoms will be eliminated only for a while, and the disease will progress.

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