Down Syndrome

In celebration of World Down Syndrome Day (21st March)

Author(s): Si Eun Lee

Introduction: What is Down syndrome? 

Down syndrome is a genetic condition caused by the presence of an extra copy of chromosomes. Individuals typically have 47 chromosomes instead of the usual 46. This additional genetic material alters normal patterns of development, leading to unique physical features, cognitive differences, and associated medical conditions. 

Chromosomes are structures made of DNA that carry genes, which act as instruction for how the body grows and functions. Having an extra chromosome means that some of these instructions are repeated, which can change how cells develop and communicate. This is why Down syndrome affects multiple systems in the body rather than just one area. 

Genetic basis and Causes

Down syndrome most commonly arises due to nondisjunction, where chromosome pairs fail to separate correctly during meiosis. This results in a gamete containing an extra copy of chromosome 21, which is then passed to the embryo at fertilization. 

Nondisjunction can occur in either the egg or sperm cell, but it is more commonly associated with the egg cell. The likelihood of this error increases with maternal age because the mechanisms that separate chromosomes during meiosis become less reliable over time. These chromosomal errors occur randomly and are not caused by parental behavior or environmental factors. They are completely sporadic. 

There are 3 main types of Down syndrome : 

• Trisomy 21 (95% of Down syndrome): caused by nondisjunction where all cells carry an extra chromosome 21. 

• Translocation Down syndrome (3-4% of Down syndrome): part or all of chromosome 21 is attached to another chromosome. 

• Mosaic Down Syndrome (1-2% of Down syndrome): only some cells contain the extra chromosome due to mitosis errors after fertilization. The condition may be less pronounced because not all cells carry the extra chromosomes, which can lead to a wider range of characteristics. 

Molecular and Physiological Effects 

Chromosome 21 contains over 200 genes. The presence of an extra copy leads to gene dosage imbalance, meaning certain proteins are overexpressed. This disrupts normal biological processes and affects multiple systems in the body. 

Key effects include: 

• Neurological development: Reduced brain volume in regions of the brain such as the hippocampus and cerebellum, contributing to difficulties in learning and memory. 

• Musculoskeletal effects: hypotonia (low muscle tone) leading to delayed development. 

• Endocrine and immune system: Increased risk of thyroid dysfunction, infections and autoimmune conditions. 

• Cardiological risks: Increased risk of congenital heart defects. Congenital heart defects are among the most common medical concerns and may require surgical treatment early in life. 

• Increased risk of early onset Alzheimer’s disease. This increased risk is linked to genes located on chromosome 21 that are involved in production of a protein called amyloid. Regular medical monitoring helps manage these conditions and improve long term health outcomes. 

Moreover, gene dosage imbalance means that proteins may be produced in higher amounts than normal, which can interfere with tightly controlled biological pathways. For example, changes in brain development can affect how neurons connect and transmit signals, influencing brain cognition and learning. Similarly, low muscle tone can impact posture and physical activity, especially during early development in childhood. 

Clinical Characteristics 

Some physical features include: 

• Small ears, hands and feet 

• Short stature and reduced muscle tone 

• Flattened facial profile and nasal bridge 

• Upwards slating eyes 

These physical characteristics are caused by differences in bone growth and muscle development. For example, hypotonia can make infants appear ‘floppy’ and may affect feeding and early movement. These features vary widely in expression and do not affect all individuals to the same degree. 

Some cognitive and developmental features include:

• Mild to moderate intellectual disability 

• Delayed speech and developmental milestones 

• Learning and memory challenges 

Cognitive development is influenced by differences in brain structure and neural connectivity. Early intervention programs, including speech therapy and specialists education, can significantly improve communication skills and learning outcomes. Many individuals develop strong social and emotional understanding, which can support development of communication and relationships. 

Diagnosis

Down syndrome can be identified before or after birth. Prenatal screening methods may indicate the likelihood of the condition, while diagnostic tests such as karyotyping confirm the presence of an extra chromosome 21. 

Screening tests estimate risk but do not provide a definitive diagnosis. Diagnostic procedures, such as amniocentesis, directly examine fetal chromosomes. After birth, physical and cognitive characteristics may suggest Down syndrome, but laboratory testing is required to confirm it. 

World Down Syndrome Day 

World Down Syndrome Day is made aware annually on 21 March (21/3), symbolizing the triplication of chromosome 21. It is recognized globally as a day to raise awareness, promote inclusion, and advocate for the rights, dignity, and well being of individuals with Down syndrome. 

Globally, Down syndrome occurs in approximately 1 in every 1000 live births, making it one of the most common chromosomal conditions. Despite this, individuals with Down syndrome often face social stigma, discrimination, and misconceptions, particularly regarding their abilities and quality of life. 

Awareness initiatives aim to challenge these misconceptions by highlighting both the scientific understanding of the condition and the lived experiences of individuals. Promoting accurate information of the condition helps reduce stigma, encourages early intervention and access to healthcare, and supports policies that foster inclusion in education and the wider community. 

Ultimately, World Down Syndrome Day is not only about recognizing the biological basis of the condition but also about reinforcing the importance of equality and representation, ensuring that individuals with Down syndrome are valued as active members of their communities.

References: 

Anthony, Kiara. “Mosaic Down Syndrome: Symptoms and Diagnosis.” Healthline, Healthline Media, 18 Sept. 2018, www.healthline.com/health/mosaic-down-syndrome. 

“Down Syndrome.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 12 Nov. 2024, www.mayoclinic.org/diseases-conditions/down-syndrome/symptoms-causes/syc-20355977. 

“Down Syndrome: Symptoms & Causes.” Cleveland Clinic, 21 Jan. 2026, my.clevelandclinic.org/health/diseases/17818-down-syndrome. 

Pal, Abhinav. “[Figure, Karyotype of down Syndrome (Trisomy...] - Statpearls - NCBI Bookshelf.” StatPearls [Internet]., U.S. National Library of Medicine, 20 Feb. 2026, www.ncbi.nlm.nih.gov/sites/books/NBK526016/figure/article-20693.image.f3/. 

“Symptoms and Causes.” Mayo Clinic, Mayo Foundation for Medical Education and Research, www.mayoclinic.org/diseases-conditions/down-syndrome/symptoms-causes/syc-20355977?p=1. Accessed 21 Mar. 2026. 

“What Causes Down Syndrome?” Eunice Kennedy Shriver National Institute of Child Health and Human Development, U.S. Department of Health and Human Services, www.nichd.nih.gov/health/topics/down/conditioninfo/causes. Accessed 21 Mar. 2026.