Down syndrome is a chromosomal condition present from birth. It is the most common chromosomal condition, affecting approximately 1 in 700 to 792 live births. It involves an alteration in chromosome 21, impacting physical development and cognitive abilities throughout an individual’s life.
The Core Genetic Change: Trisomy 21
Human cells typically contain 23 pairs of chromosomes, totaling 46, with half inherited from each parent. In most cases of Down syndrome, individuals have 47 chromosomes in each cell instead of the usual 46, specifically an additional chromosome at position 21. This condition is medically termed Trisomy 21 (ICD-10-CM: Q90.9).
A chromosome is a rod-like structure located within the nucleus of every cell, carrying genes that determine inherited traits. This extra genetic material from chromosome 21 disrupts the delicate balance of gene expression, leading to the characteristic physical features and developmental differences observed in individuals with Down syndrome.
Understanding the Genetic Variations
The extra genetic material that causes Down syndrome can arise from three distinct genetic variations. Each type involves an additional copy of chromosome 21 or a significant portion of it, but the mechanism by which this occurs differs.
The most common form, accounting for approximately 95% of cases, is called Standard Trisomy 21. This occurs due to an error in cell division known as nondisjunction. Nondisjunction happens when a pair of chromosome 21s in either the egg or sperm cell fails to separate properly during meiosis, the process of forming reproductive cells. Consequently, the resulting egg or sperm has two copies of chromosome 21 instead of one, leading to three copies of chromosome 21 in every cell of the developing embryo after fertilization.
Another type is Translocation Down Syndrome, which accounts for about 3% to 4% of cases. In this variation, a portion of chromosome 21 breaks off and attaches to another chromosome, often chromosome 14, either before or at conception. While the total number of chromosomes might remain 46, the extra chromosome 21 material attached to another chromosome leads to the characteristics of Down syndrome. This type can sometimes be inherited if a parent carries a balanced translocation, meaning they have the rearranged chromosomes but no extra genetic material, thus showing no symptoms themselves.
The rarest form is Mosaic Down Syndrome, affecting about 1% to 2% of individuals with the condition. Mosaicism occurs when nondisjunction happens in an early cell division after fertilization. This results in a mixture of cell types within the same individual: some cells have the typical 46 chromosomes, while others have the extra copy of chromosome 21. The varying proportion of cells with the extra chromosome can lead to a spectrum of characteristics.
Occurrence and Genetic Factors
Down syndrome occurs globally, affecting individuals across all racial and socioeconomic backgrounds. It is not caused by environmental factors or parental activities before or during pregnancy. The occurrence is largely a random event during cell division.
Maternal age is the most significant known factor influencing the likelihood of having a child with Down syndrome, particularly for cases resulting from nondisjunction. The risk increases as the mother ages, with older eggs having a greater chance of unusual chromosome division. For example, the incidence increases from less than 0.1% for 20-year-old mothers to about 3% for those aged 45. Despite this, a substantial number of babies with Down syndrome, often around 51% to 80%, are born to women under 35 years of age due to higher birth rates in this younger demographic.
Most cases of Down syndrome are not inherited. Standard Trisomy 21 and Mosaic Down Syndrome typically arise from random errors in cell division and are not passed down through families. Translocation Down Syndrome, however, can be an exception; approximately one-third of translocation cases are inherited from a parent who is a carrier of a balanced translocation. These carrier parents do not have Down syndrome symptoms themselves but can pass on the genetic rearrangement.