Down’s Syndrome

Down’s syndrome is a genetic condition in which a person has one extra copy of chromosome 21. This is why this syndrome is also called “trisomy 21” (Down’s syndrome trisomy 21). This genetic anomaly causes changes and differences in how the baby develops, both mentally and physically. Some characteristics are common in all people with Down’s syndrome, especially physical and physiological characteristics, but there are also differences regarding their mental abilities, such as their IQ.

Before we dive in into the subject of genetics and symptoms of Down’s syndrome, let’s have a quick look at some history facts regarding this subject.

Down’s Syndrome History

This syndrome was first described in 1866 by John Langdon Haydon Down, a British doctor that stated that the syndrome is characterized by three main things: particular dysmorphic characteristics, chromosomal aberration and mental retardation. Even though this condition was believed to be caused by some chromosomal abnormalities since the 19th century, it was not until 1959 when Jerome Lejeune, a French geneticist, discovered the true cause of Down’s syndrome: the presence of an extra copy of chromosome 21, adding one more chromosome for those patients who will have a total of 47 chromosomes instead of 46 (which is the normal number of chromosomes in humans).

Down's Syndrome genetics

What are chromosomes and how does genetics affect the development of a baby? Chromosomes are molecules that contain information about every characteristic of the human body. One chromosome is made up of protein and DNA which is basically the manual with genetic instructions that is inherited from the parents. One person typically has 44 chromosomes like these, that are organized in pairs, resulting in 22 chromosome pairs that are also known as autosomes. Additionally, humans have one more pair of chromosomes, X and Y, called the sex chromosomes because their combinations determine one’s sex – XX for females and XY for males.

So how does one person get its chromosomes? This all starts with the moment an egg from the biological mother is fertilized by a sperm from the biological father. The cells in the egg and sperm are also known as gametes and they are produced during the process of cell division, called meiosis. This means that gametes have 23 chromosomes, so half the number, with one of them being either X or Y. Gametes from the mother only have the X chromosome, while gametes from the father usually are divided – half of them have the X chromosome and the other half the Y chromosome. In the process of fertilization, female gametes combine with male gametes to produce a zygote that will have two sets of 23 chromosomes, adding up to the number of 46 chromosomes that is considered normal in humans. Usually, the terminology is that women are 46XX and males 46 XY. This, however, can vary due to the fact that the process of meiosis and then fertilization is a very complex one and it requires a lot of steps that can sometimes be influenced negatively by different factors (individual or environmental) that will result in mutations or chromosomal variations.

The 21st chromosome – Down syndrome 21st chromosome

Down’s syndrome is a chromosomal condition so what exactly happens with Down’s syndrome chromosomes? We’ve established that humans typically have 23 pairs of chromosomes, so that means every cell in the body has 46 chromosomes, half from the biological mother, half from the biological father. Chromosome 21 is the smallest in humans, making up approximately 2% of the DNA in humans. Researchers have tried to identify the number of genes in each chromosome and what they are responsible for, and in the case of the 21st chromosome, they have estimated a number of 200 to 300 genes. What these genes do is that they give instructions for manufacturing proteins which are essentials molecules that have different functions within a cell (this process of protein genesis has two big steps known as transcription and translation).

Given the fact that the number of chromosomes can vary of that there are different chromosomal anomalies, there are a few conditions associated with chromosome 21:

Down’s syndrome – the most common one and the subject of this article; this is a genetic condition usually caused by the presence of one more chromosome 21 in each cell, instead of the typical pair; there are also other ways in which chromosome 21 can cause Down’s syndrome and we will go deeper into this subject later on when we discuss the types of Down’s syndrome;
Core binding factor acute myeloid leukemia – this type of blood cancer is caused by the translocation of genes (chromosomes exchange genes between themselves) between chromosome 21 and chromosome 8; this type of leukemia is not inherited, but it’s a genetic mutation that occurs during someone’s life and is present only in some cells, not all; it usually occurs in adults;
Acute lymphoblastic leukemia – another type of blood cancer which is determined by the translocation of genes between chromosome 21 and chromosome 12; it’s usually diagnosed in children.

Down's syndrome types

Even though we’ve mostly talked about the fact that Down’s syndrome is a trisomy, there are two more ways in which chromosome 21 can cause this type of genetic condition. The three types of Down’s syndrome are trisomy 21, translocation Down’s syndrome and mosaic Down’s syndrome.

Trisomy 21. This is the most common type of Down’s syndrome, with almost 95% percent of cases of this condition being caused by the presence of an extra chromosome 21 in every cell in the body, instead of the usual pair.

Translocation Down’s syndrome. This is a rarer type, with approximately 3% of babies born with Down’s syndrome having this genetic condition. What happens is that the baby still has three copies of chromosome 21, but one of them is usually attached to another chromosome, such as chromosome 3, 14, 15 or 22. In some other rare cases, two chromosomes 21 can attach to each other and it would still result in translocation Down’s syndrome. This condition can be inherited from one of the parents if they are what is called a balanced translocation carrier. This means that the parent has a translocation chromosome, meaning they have 45 chromosomes in each cell, but they don’t have any health conditions or physical characteristics associated with this, they are “normal”. How can this be possible? It’s simple, even though this person only has 45 chromosomes, they actually have all copies of chromosomes required for a healthy, normal individual; it’s just that two of their chromosomes are attached to each other. There aren’t significant differences in symptomatology between babies with trisomy 21 and translocation Down’s syndrome.

Mosaic Down’s syndrome. This condition is also called mosaicism and it’s the rarest form of Down’s syndrome, with only approximately 2% of the cases of this condition being caused by mosaicism. If in the cases of trisomy 21 or translocation Down’s syndrome all the cells in the body had three copies of chromosome 21, in this case only some cells have an extra chromosome, resulting in a mix of cells, just like a mosaic. The cause for this typically is that the division that leads to one more chromosome 21 occurs after the moment of fertilization. As far as the symptoms go, people with mosaic Down’s syndrome are at risk of all the symptoms people with trisomy 21 or translocation Down’s syndrome have. However, considering that in the case of mosaicism, some cells in the body are healthy (meaning they have the normal amount of 46 chromosomes), they can experience less symptoms compared to the people who have the other two types of Down’s syndrome. For instance, individuals with mosaic Down’s syndrome usually score higher in IQ tests than individuals with the other two types of this condition.

Can Down’s syndrome be inherited?

We’ve seen the three types of Down’s syndrome and what causes them, but a relevant questions arises: can this genetic condition be inherited? Usually, no, considering it’s caused by something going wrong with the chromosomes during cell division after fertilization. However, in the case of translocation Down’s syndrome it is possible to inherit the extra chromosome 21 attached to another chromosome from one of the parents (usually the mother).

Down's syndrome symptoms and signs

Down’s syndrome symptoms

Down’s syndrome effects, symptoms and signs make this condition one that can be very easily recognized, even for someone who isn’t a professional in the field of medicine. While there are some distinctive facial features common in all people with Down’s syndrome, the intellectual abilities and health conditions associated with this syndrome can vary from one person to another.

Some of the most common distinctive physical features of Down’s syndrome are: flattened face, short neck, small head, almond-shaped eyes with upward slanting lids called palpebral fissures (Down’s syndrome eyes), white spots on the iris (known as Brushfield’s spots), protruding tongue (their tongue tends to stick out most of the times), small ears, hands and feet, broad palms with palmar crease (just one line across the palm of the hand), poor muscle tonus, loose joints. Even though at smaller ages, kids with Down’s syndrome can have an average size, their growth process is slower and they usually stay shorter than kids their age.

Some other effects of this genetic condition are developmental delays and behavioral difficulties. Speech and language in particular may develop slowly and later compared to children the same age that don’t have Down’s syndrome; speech can sometimes be difficult to understand as well. Some of the behavioral difficulties in people with Down’s syndrome can be attention problems, a stubborn and neurotic personality or obsessive-compulsive behaviors.

Down’s syndrome complications

As they get older, people with Down’s syndrome are at high risk of developing some serious health complications, such as:

heart defect – almost half of babies born with Down’s syndrome are also born with potentially life-threatening heart conditions (Down’s syndrome heart defect) that could require surgery and treatment at early ages;
digestive abnormalities or gastrointestinal defects – these are less common; they can mean blockage in the intestines, gastroesophageal reflux (heartburn), celiac disease (intolerance to gluten, a protein found in wheat);
hypothyroidism – approximately 10% of people born with Down’s syndrome also have hypothyroidism, which means that their thyroid gland is underactive; this can lead to fatigue, weight changes, irritability or poorer mental health;
immune disorders – the immune system of a person with Down’s syndrome can be quite fragile, which means that they are at risk of developing autoimmune diseases or infectious diseases (e.g. pneumonia);
leukemia – a small percentage of kids born with Down’s syndrome also develop a form of blood cancer known as leukemia; the most common types of leukemia in this case are megakaryoblastic leukemia and acute lymphoblastic leukemia;
diabetes – this is a medical condition that marks the body’s incapacity of regulating sugar levels through insulin; there are two types of diabetes common in people with Down’s syndrome, type 1 diabetes and type 2 diabetes; type 1 diabetes is an endocrine and autoimmune disease characterized by low production of insulin by the pancreas; it’s more commonly diagnosed during childhood; type 2 diabetes is characterized by a resistance to insulin; research shows that this type of diabetes is also more prevalent at younger ages in people with Down’s syndrome, being associated also with obesity;
obesity – compared with the general population, individuals with Down’s syndrome are at a higher risk of becoming obese;
sleep apnea – kids and adults with Down’s syndrome can get obstructive sleep apnea caused by the obstruction of the airways; this is related to skeletal and tissue changes specific to Down’s syndrome;
atlantoaxial instability – this means that the first two vertebrae in the neck are misaligned which can cause overextension of the neck; this is a serious condition that needs proper attention;
hearing loss, vision difficulties and problems (such as cataracts), dental issues.

Mental health concerns related to Down’s syndrome

Given the personal characteristics of a person with Down’s syndrome and their risk of developing different physical and physiological conditions, they are at great risk of also having mental health issues, such as anxiety and general anxiety, depression, obsessive-compulsive disorder, difficulties related to sleep, autism and progressive neuropsychological loss. All these depend very much on the age and individual characteristics.

Small children. This age group is predisposed to communication and cognitive difficulties, disruptive, impulsive and hyperactive behaviors, anxiety, rumination, repetitive behaviors, fatigue and sleep difficulties.
Adolescents and young adults. These people are at risk for depression, generalized anxiety, obsessive-compulsive behaviors, decline in cognitive and social skills, sleep difficulties.
Older adults. This age group is vulnerable to the same conditions as the others, the decline in cognitive and social skills being faster, with dementia becoming a prevalent condition.

Down's syndrome and autism

One mental health condition that is relatively high in prevalence in people with Down’s syndrome is autism. In the medical field the co-occurrence of these conditions is known as a dual diagnosis. Some of the symptoms and signs of people who have this dual diagnosis (Down’s syndrome and autism) are difficulties in changing routine patterns, stereotypical behaviors, challenged communication skills, higher preoccupation with rituals and higher levels of hyperactivity, conduct problems and different degrees of learning disabilities.

Down's syndrome lifespan

Considering the amount and variety of health conditions associated with Down’s syndrome, one can become curious about what is the life expectancy for individuals with this genetic syndrome. According to scientists, in the ‘60s, on average, people with Down’s syndrome had a life expectancy of only 10 years old. More recently, in 2007, on average, this number increased exponentially to 47 years old. This statistic begs the question if there are some factors that contribute to how long someone with Down’s syndrome can live and of course research is here to deliver. Some of these factors include weight at birth, race (with black or African-American babies with Down’s syndrome having a lower chance of surviving past the first year compared to white babies) or whether or not the babies are born with congenital heart defects.

Down's syndrome risk factors

Down’s syndrome risk

One major Down’s syndrome risk factor is the mother’s age, with women (Down's syndrome woman) at the age of 35 or older being more at risk of having a baby with Down’s syndrome. This is largely due to the fact that older eggs have higher chances of experiencing difficulties in the division process. In the case of translocation Down’s syndrome, one risk factor is the presence of the translocation in one of the parents.

Down's syndrome diagnosis

Right now, there are two types of tests that can detect Down’s syndrome while a woman is pregnant (Down's syndrome pregnancy) which are: screening tests and diagnostic tests:

Screening tests. These tests cannot detect with 100% accuracy if the baby has Down’s syndrome, so they cannot provide a definite diagnosis. What these tests do is that they can predict a higher or lower chance of the baby to have this genetic condition. Among screening tests there are usually blood tests (Down's syndrome blood test) which can provide levels of different substances in the mother’s blood that are of interest.

Another type of screening tests is the ultrasound, which gives a picture of the baby (Down syndrome ultrasound 3D; Down syndrome 4D ultrasound). The ultrasound can show if there is extra fluid in the region behind the baby’s neck (nuchal translucency) which is typically an indicator of a genetic condition. This scan is usually performed between weeks 10 and 14 of pregnancy (Down syndrome 11 week ultrasound; Down syndrome 12 week ultrasound).

Blood tests and ultrasounds and their results are to be taken with precaution because one cannot rely entirely on the precision of a diagnosis made solely on these two screening tests. However, their advantage is that these tests are much safer for the mother and the baby.

Diagnostic tests. These tests can usually diagnose Down’s syndrome in a baby, but they are quite risky. Diagnostic tests typically follow a positive screening test for a confirmation of the diagnosis. These tests look for changes in the chromosome number in the cells and examine the placenta (chorionic villus sampling), the amniotic fluid (amniocentesis) or the blood from the umbilical cord (percutaneous umbilical blood sampling). Diagnostic tests come with risk of miscarriage which is why women hesitate before going down this road.

Down's syndrome markers

Among some of the markers of Down’s syndrome that can be assessed during an ultrasound in the second trimester of the pregnancy, there are ventricles in the brain that are dilated, nose bone that is absent or small, fluid at the back of the neck, bright spots in the heart region, swelling of the kidneys, a shorter arm or thigh bone.

Down’s syndrome – prevention?

Unfortunately, there isn’t much to be done to prevent Down’s syndrome. Given the fact that this genetic condition occurs because of the presence of an extra copy of chromosome 21 as a result of cell division difficulties, prevention is not really an option. However, we’ve seen that in the case of translocation being the cause of Down’s syndrome, parents can benefit from a consultation with a genetic counselor before getting pregnant, in order to see what are their chances of having the translocation and passing it down to a potential baby. This is also the case for parents who already have a child with Down’s syndrome.

Conclusion

Down’s syndrome is a genetic condition that has become more prevalent in recent times. It has also gained quite a large body of research which has allowed for people living with this condition to live longer and more qualitative lives if themselves and their parents have access to the right resources.