What is Down Syndrome?
Down Syndrome was first identified by an English doctor named John Langdon Down in 1866. However, the link between Down Syndrome and chromosome 21 wasn’t established until almost a century later by Dr. Jerome Lejeune in Paris. Down Syndrome is caused by having an extra part or a full extra copy of chromosome 21. This makes Down Syndrome the most common genetic anomaly found in humans. It’s important to note that the most common genetic irregularity found in newborns is also caused by an extra copy of chromosome 21, which results in Down Syndrome.
What Causes Down Syndrome?
Most individuals with Down syndrome have an extra copy of a specific portion of the DNA, called chromosome 21. There are various theories about why this happens and how different genetic features link with the characteristics of Down syndrome.
One of these theories is the gene dosage imbalance, which suggests that there is a higher number of genes in the chromosome 21, leading to expansion of these genes. Different genes might be connected with different features of Down syndrome.
Another theory is the amplified development instability hypothesis. This suggests that the genetic imbalance created by a larger number of genes results in a significant impact on the regulation and activity of many other genes.
Another well-known theory is based on Down syndrome critical regions (DSCR), particular parts of chromosome 21. These regions are often associated with Down syndrome and are responsible for many of its clinical features.
But, studies have shown that a single gene can’t cause all the features associated with Down syndrome. Instead, it seems that multiple genes or regions play a role in the syndrome.
Risk Factors and Frequency for Down Syndrome
Down syndrome is a condition that becomes more common as the mother’s age increases. The number of cases varies among different population groups, ranging from 1 in 319 to 1 in 1000 live births. It’s important to understand that a high number of fetuses have Down syndrome at the time of conception, but about half to three-quarters of them do not make it to term. There are other conditions similar to Down syndrome, and they’re more common, but unfortunately, their survival rate after birth is very poor compared to Down syndrome. Surprisingly, those with Down syndrome, which is caused by an extra copy of chromosome 21, have a higher chance of survival because this chromosome has fewer genes.
Signs and Symptoms of Down Syndrome
Down syndrome affects multiple systems in the body, leading to a variety of different symptoms. People with Down syndrome can show signs of intellectual and developmental difficulties, characteristic facial features, heart defects, gastrointestinal problems, and other irregularities.
One of the biggest health concerns for people with Down syndrome, especially during the first two years of life, is congenital heart defects. Up to 50% of babies born with Down syndrome have some type of heart defect. The most common are atrioventricular septal defect and ventricular septal defect. Other less common heart defects can also occur. Due to the high prevalence of these heart defects in Down syndrome, it is usually recommended that all patients get a heart ultrasound within the first few weeks of life.
People with Down syndrome can also have many structural and functional disorders related to the gastrointestinal tract. These can range from structural defects in any part of the digestive system to functional disorders like gastroesophageal reflux disease, chronic constipation, occasional diarrhea, and celiac disease. Screening for celiac disease is recommended on an annual basis. If diagnosed with this disease, a gluten-free diet will be necessary for the individual’s entire life.
Down syndrome is also linked to multiple blood disorders. Some disorders occur more often in people with Down syndrome and need to be monitored closely, like a type of blood disorder that usually resolves by itself within the first three months of life. More severe disorders, like leukemia, can also occur more frequently in people with Down syndrome.
- Intellectual and developmental difficulties
- Heart defects
- Gastrointestinal problems
- Blood disorders
Down syndrome also affects the nervous system which can lead to various neurological disorders. Almost all people with Down syndrome experience decreased muscle tone, which can lead to delayed motor development. As a result of this decreased muscle tone, individuals with Down syndrome often have loose joints and can be prone to dislocations. In some cases, individuals may experience seizures or develop dementia earlier in life than the general population.
Thyroid gland dysfunction, particularly hypothyroidism, often occurs with Down syndrome. For some people with Down syndrome, puberty may be delayed, or individuals may experience other disorders related to sexual development.
People with Down syndrome typically have reduced muscle mass due to decreased muscle tone and increased joint looseness. This can slow down the development of large motor skills and can lead to dislocations of the joints.
Various eye problems are common in individuals with Down syndrome. These can range from inflammation of the eye lids (blepharitis) to keratoconus, cataract, crossed or lazy eyes (strabismus), and a decreased ability to see fine detail (refractive defects).
Ear, nose, and throat problems are also common in Down syndrome. The structural characteristics of the ear in these individuals often leads to hearing issues. As well, there may be structural abnormalities in the inner ears which can lead to hearing loss.
Testing for Down Syndrome
Various methods are used to test for Down syndrome during pregnancy. Typically, an ultrasound is used between 14 and 24 weeks of pregnancy. It looks for certain “soft markers” such as increased thickness in the back of the baby’s neck, a small or absent nasal bone, and larger-than-normal brain ventricles. However, these markers can also indicate other conditions like Patau syndrome, Edwards syndrome, or Turner syndrome.
Between 11 and 14 weeks of pregnancy, an ultrasound can detect ‘nuchal translucency’ (NT), which is a build-up of fluid in the neck of the fetus. More invasive tests like amniocentesis and chorionic villus sampling can also be used, but these come with a small risk of miscarriage – between 0.5% and 1%.
Other methods exist for quickly detecting Down syndrome either during pregnancy or after the baby is born. For example, the FISH test uses probes to highlight chromosomes on Hsa21 (the chromosome implicated in Down syndrome). QF-PCR is another test that looks for the presence of three different gene segments. The success of this method relies on the presence of certain gene markers and DNA. Almost 87% of Down syndrome cases can be identified using the STR marker method.
Newer methods are currently in development. For example, ‘paralogue sequence quantification’ (PSQ) is a PCR-based technique that uses certain genes to detect abnormalities in chromosome numbers. This technique is being adapted for use in diagnosing Down syndrome.
Non-invasive methods are also being studied. These methods are based on the presence of fetal cells and cell-free fetal DNA in the mother’s blood. However, cell-free fetal DNA makes up only 5-10% of the mother’s blood, and though it’s been used to determine factors like the baby’s Rh status and sex, using it to detect chromosomal abnormalities like Down syndrome is still challenging.
New approaches, such as digital PCR and next-generation sequencing (NGS), are being developed for the diagnosis of Down syndrome. This ongoing research continues to improve the accuracy and speed of Down syndrome diagnosis.
Treatment Options for Down Syndrome
Managing patients with Down syndrome requires a team of various healthcare professionals. If a newborn is suspected to have Down syndrome, a test called karyotyping is done to confirm the diagnosis. Both parents are then referred to a genetic specialist to further understand and counsel them about the condition.
Parent education is a crucial part of Down syndrome management. Parents need to understand the potential health conditions associated with Down syndrome so they can help recognize and address them appropriately. Treatment primarily focuses on managing the symptoms, as complete recovery from Down syndrome isn’t possible.
Patient’s vision and hearing checks are important, especially as they have a higher chance of developing cataracts. Surgery is required to treat cataracts in a timely manner. Regular thyroid tests, typically performed yearly, are important too. If results show issues with thyroid function, these should be managed as needed.
A balanced diet, regular exercise, and physical therapy can help these patients grow healthily and manage their weight. For some of these patients, particularly those with cardiac issues, their ability to eat can significantly improve after they have heart surgery.
All patients with Down syndrome should be checked for potential heart defects, even if they don’t show any signs of them. If heart defects are detected, surgical procedures should be performed within the first six months of the child’s life. This helps to ensure the best growth and development.
The team of specialists that may be involved in treating a child with Down syndrome can include pediatricians specializing in development, lung and stomach issues, neurology, orthopedics, psychiatry, along with physical and occupational therapists, speech and language therapists, and audiologists.
What else can Down Syndrome be?
Conditions that arise from birth or are genetically linked:
- Birth hypothyroidism (commonly referred to as Congenital hypothyroidism)
- Mosaic trisomy 21 syndrome (a type of Down syndrome)
- Partial trisomy 21 (or 21q duplication, another form of Down syndrome)
- Robertsonian trisomy 21 (yet another variant of Down syndrome)
- Trisomy 18 (also known as Edwards syndrome)
- Zellweger syndrome or other disorders linked to peroxisomes (parts of your cells that assist with various vital bodily functions)
What to expect with Down Syndrome
Due to recent advancements in medical practices, better surgical techniques for correcting congenital defects, and improved overall care, the survival rates of infants and life expectancy for those living with Down syndrome have dramatically increased.
For example, a study from Birmingham (UK) conducted about 60 years ago revealed that only 45% of infants survived their first year, and by the age of five, the survival rate dropped to 40%. However, a similar study done about 50 years later showed significant improvements. In this study, 78% of Down syndrome patients with a congenital heart defect survived their first year. Moreover, the survival rate jumped to 96% for those without the added complications of a heart defect.
This increase in life expectancy is expected to continue rising significantly due to continual medical advancements. The ultimate goal for healthcare facilities is to administer appropriate and timely treatment to these patients, helping them live fulfilling, productive lives.