Introduction:
Down syndrome is a genetic disorder that occurs when there is an extra copy of chromosome 21. Chromosomes are structures that contain genetic information, and most people have 23 pairs of them. However, people with Down syndrome have three copies of chromosome 21 instead of two, which results in certain physical and cognitive characteristics.
Down syndrome was first identified in 1866 by an English physician named John Langdon Down, but its link to chromosome 21 was established nearly 100 years later by Dr. Jerome Lejeune in Paris. Down syndrome, the most prevalent chromosomal anomaly in humans, is caused by the presence of all or part of the third copy of chromosome 21. It has also been shown that the most common live born aneuploidy that causes this disease is trisomy 21.
Prevalence:
In general, Down syndrome occurs in approximately 1 in 700 live births. It is the most common chromosomal disorder, and it affects people of all races and ethnicities.
The prevalence of Down syndrome rises with maternal age and varies by population (1 in 319 to 1 in 1000 live births). It is also known that the frequency of Down syndrome fetuses is fairly high at the time of conception, but approximately 50% to 75% of these fetuses are lost before term. Other autosomal trisomies are far more common than the 21, although postnatal survival is much lower when compared to Down syndrome. This exceptional survival rate of trisomy 21 patients is assumed to be due to a tiny number of genes on chromosome 21 called Hsa21, which is the smallest and least dense of the autosomes.
Types:
There are three types of Down syndrome: trisomy 21, mosaicism, and translocation.
Each type of Down syndrome can have varying degrees of severity and may result in different physical and cognitive characteristics.
Trisomy 21
This is the most common type of Down syndrome, accounting for about 95% of cases. It occurs when there is an extra copy of chromosome 21 in every cell of the body. Trisomy 21 is usually not inherited and occurs spontaneously during the formation of the reproductive cells or early in embryonic development.
Fig: Karyotyping with Trisomy 21 (Down syndrome)
Mosaicism:
This type of Down syndrome occurs when there is a mixture of cells in the body, some with the usual two copies of chromosome 21 and others with three copies. This occurs because the extra chromosome 21 is present in some but not all of the cells. Mosaicism accounts for about 1% of cases of Down syndrome.
Translocation
In this type of Down syndrome, a part of chromosome 21 breaks off during cell division and attaches to another chromosome, usually chromosome 14. Although the total number of chromosomes is still 46, there is extra genetic material from chromosome 21 attached to another chromosome. Translocation accounts for about 4% of cases of Down syndrome and can be inherited from a parent who carries a balanced translocation.
Pathophysiology:
Down syndrome is a genetic disorder caused by the presence of an extra copy of chromosome 21, leading to a total of three copies instead of the usual two copies. This results in a range of physical and intellectual disabilities. The most prevalent cause of Down syndrome is trisomy 21, which is an extra copy of chromosome 21 in all cells produced by a chromosomal non-disjunction during meiosis. Increased transcription of oncogenes and tumour suppressor genes on human chromosome 21 causes transcriptional changes of various molecular pathways involved in Down syndrome-related disorders such as cell cycle disruption, leukaemia, tumours, and cancer.
Symptoms and complications:
Down syndrome is a genetic disorder that affects multiple organ systems and can cause a range of physical and intellectual disabilities. The symptoms and complications of Down syndrome can vary widely between individuals, and early intervention and treatment can help manage these symptoms and improve outcomes.
Intellectual disability: Individuals with Down syndrome often have varying degrees of intellectual disability, ranging from mild to severe.
Developmental delays: Due to the extra chromosome 21, children with Down syndrome often have delayed development of speech, motor skills, and cognitive abilities.
Physical features: Down syndrome can cause a range of physical features, including a small head, upward slanting eyes, a flat facial profile, a single crease across the palm, and poor muscle tone.
Congenital heart defects: Heart defects are common in individuals with Down syndrome and can range from mild to severe.
Gastrointestinal problems: Individuals with Down Syndrome are at an increased risk of developing certain gastrointestinal problems, which can affect the digestive system and cause discomfort and other health issues. Some of the most common gastrointestinal problems associated with Down Syndrome include gastroesophageal reflux disease (GERD), constipation, celiac disease, Hirschsprung’s disease, and intestinal blockages. These problems may be related to genetic factors or other underlying health issues such as low muscle tone or immune system dysfunction. Management of gastrointestinal problems in individuals with Down Syndrome typically involves dietary changes, medication, or surgery when needed. Regular check-ups with a healthcare provider who is familiar with the potential gastrointestinal problems associated with Down Syndrome are important for early detection and appropriate treatment, which can help manage these issues and improve the overall quality of life for individuals with Down Syndrome.
Respiratory infections: Individuals with Down syndrome are more susceptible to respiratory infections, such as pneumonia and bronchitis.
Hearing and vision problems: Hearing and vision problems are common in individuals with Down syndrome.
Thyroid problems: Individuals with Down syndrome are at an increased risk of developing thyroid problems, such as hypothyroidism.
Hypertension: People with Down Syndrome are predisposed to hypertension, generally known as high blood pressure. Hypertension is a common medical condition that can lead to major problems like heart disease, stroke, and renal failure. Individuals with Down Syndrome may be predisposed to hypertension due to hereditary reasons or other underlying health conditions such as obesity, sleep apnea, and thyroid dysfunction. Those with Down Syndrome who have hypertension are normally managed with lifestyle changes such as a good diet, frequent exercise, and weight management, as well as medication when necessary.
Haematological problems: Down Syndrome is a genetic condition that increases the chance of certain haematological abnormalities involving blood and blood-forming cells. Leukaemia, megakaryocytic leukaemia, transitory myeloproliferative condition, immune system dysfunction, and anaemia are the most prevalent haematological issues linked with Down Syndrome. Due to genetic factors, immune system dysfunction, or other underlying health difficulties, people with Down Syndrome may be predisposed to several illnesses. Frequent check-ups with a healthcare professional aware with the potential haematological disorders associated with Down Syndrome are critical for early detection and appropriate treatment, which can help control these concerns and enhance the overall quality of life for people with Down Syndrome.
Neurological problems: Down Syndrome is a genetic abnormality that can result in a variety of neurological issues due to an extra copy of chromosome 21 carried by persons with the condition. Intellectual disability, developmental delays, autism spectrum disorder, seizures, sleep apnea, Alzheimer’s disease, and hearing and visual issues are the most prevalent neurological problems linked with Down Syndrome. However, not all people with Down Syndrome may experience all of these issues, and the severity might vary greatly between people. Early intervention and suitable therapy can help individuals with Down Syndrome manage these challenges and enhance their overall quality of life.
Diagnosis:
There are several different diagnostic methods for Down syndrome. It is important to note that the prenatal testing methods are used to determine the likelihood that a fetus may have Down syndrome, while the postnatal testing methods are used to confirm a diagnosis of Down syndrome in an individual who has already been born. It is important to note that all diagnostic tests carry a small risk of miscarriage, so the decision to undergo testing should be made in consultation with a healthcare provider.
| Diagnosis Method | Prenatal or Postnatal | Description |
| Maternal Serum Screening | Prenatal | A blood test that measures the levels of certain proteins and hormones in the mother’s blood to assess the risk of Down syndrome. |
| Non-invasive prenatal testing (NIPT) | Prenatal | A blood test that analyses fragments of fetal DNA that circulate in the mother’s blood. It is highly accurate and can detect Down syndrome with a very low false-positive rate. |
| Ultrasound | Prenatal | An imaging test that can detect physical characteristics associated with Down syndrome, such as an enlarged nuchal fold or abnormal facial features. |
| Amniocentesis | Prenatal | A procedure that involves taking a sample of amniotic fluid from around the fetus and analysing the fetal cells for the presence of extra genetic material. |
| Chorionic Villus Sampling (CVS) | Prenatal | A procedure that involves taking a sample of placental tissue and analysing the cells for the presence of extra genetic material. |
| Percutaneous Umbilical Blood Sampling (PUBS) | Prenatal | A procedure that involves taking a sample of fetal blood from the umbilical cord and analysing the cells for the presence of extra genetic material. |
| Chromosome Analysis | Postnatal | A blood test that analyses the number and structure of chromosomes in a person’s cells to determine if they have Down syndrome. |
| Microarray Analysis | Postnatal | A genetic test that can detect extra or missing genetic material associated with Down syndrome. |
| Fluorescent In Situ Hybridization (FISH) | Postnatal | A laboratory technique that can quickly detect the presence of extra genetic material associated with Down syndrome in a person’s cells. |
Treatment and Prevention:
Down Syndrome is a genetic disorder that is caused by an extra copy of chromosome 21. There is no cure for Down Syndrome, but there are various treatments and therapies that can help individuals with Down Syndrome to live healthy and fulfilling lives.
Early intervention is key in managing Down Syndrome, and it should begin as early as possible. Some of the treatments and therapies that can help individuals with Down Syndrome include:
Speech therapy: Many individuals with Down Syndrome have speech and language difficulties, and speech therapy can help them to improve their communication skills.
Occupational therapy: This type of therapy can help individuals with Down Syndrome to develop fine motor skills, sensory integration, and self-care skills.
Physical therapy: Physical therapy can help individuals with Down Syndrome to improve their strength, balance, and coordination.
Special education: Children with Down Syndrome may benefit from specialized education programs that cater to their unique learning needs.
Behavioural therapy: This type of therapy can help individuals with Down Syndrome to learn social skills, improve their behaviour, and manage any emotional or behavioural issues.
In terms of prevention, there is no way to prevent the genetic mutation that causes Down Syndrome. However, prenatal testing can be performed during pregnancy to detect the condition. This can help expectant parents to prepare for the arrival of a child with Down Syndrome and access any necessary treatments and therapies.
While, there is no cure for Down Syndrome, early intervention, and access to treatments and therapies can help individuals with Down Syndrome to live healthy and fulfilling lives. Prenatal testing can also help expectant parents to prepare for the arrival of a child with Down Syndrome.
World Down Syndrome Day:
World Down Syndrome Day is celebrated every year on March 21st. It is a global awareness day that aims to promote understanding and acceptance of people with Down syndrome, raise awareness of their abilities and challenges, and advocate for their rights and inclusion in society.
The date 21st March (3/21) was chosen because it represents the unique genetic makeup of individuals with Down syndrome, who have three copies of the 21st chromosome instead of the usual two.
The theme of World Down Syndrome Day changes every year, but it always focuses on raising awareness and promoting the inclusion of people with Down syndrome. Many events and activities are organized around the world to celebrate this day, including conferences, workshops, sports events, and social gatherings.
It is an important opportunity to celebrate diversity and raise awareness about the valuable contributions that people with Down syndrome make to their communities.
References
- Rachidi M, Lopes C (2007) Mental retardation in Down syndrome: From gene dosage imbalance to molecular and cellular mechanisms. Neuroscience Research 59: 349-369
- Akhtar, F. and Bokhari, S.R.A., 2020. Down syndrome (trisomy 21). U: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.
- Asim, A., Kumar, A., Muthuswamy, S. et al. “Down syndrome: an insight of the disease”. J Biomed Sci 22, 41 (2015)