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Pioneering innovative therapies to improve the lives of those with genetic intellectual disabilities

Trisomy 21 (Down syndrome)

What is Trisomy 21, or Down Syndrome?

A trisomy occurs when there is an error in the division of the sperm or egg cell causing one of the pairs of chromosomes to not divide. The result at conception is that three copies of a chromosome appear in the newly conceived individual rather than two. The most familiar and most common trisomy occurs on chromosome 21 and is commonly called Down syndrome. But a trisomy can happen on any chromosome. Other less common trisomies occurs on chromosome 18, known as Edwards syndrome, and on chromosome 13, commonly called Patau syndrome. Individuals with Down syndrome are more common because those conceived with an extra 21st chromosome have a greater chance of surviving into adulthood. Most babies conceived with trisomies on other chromosomes are miscarried, or die soon after birth. Jerome Lejeune also discovered trisomies on chromosomes 8 and 9.

Down syndrome occurs in approximately 1 in 792 live births in the U.S. (deGraaf et al. [2015] "Estimates of live births, natural losses, and elective terminations with Down syndrome in the United States." Am J Med Genet Part A 167A: 756-767) and is the most common genetic cause of intellectual disability. It is uncertain how many individuals in the U.S. are living with Down syndrome. It was long thought that the disability affected some 400,000 individuals, but new estimates put the number closer to 250,000 (Presson et al. "Current estimate of Down syndrome population prevalence in the United States" J Pediatr. 2013 Oct; 163[4]: 1163-8).  Worldwide, it is believed that there are around 6 million people living with Down syndrome.

It is commonly thought that Down syndrome occurs most frequently in children born of older mothers. While it is true that Down syndrome births are a larger percent of births among older mothers, about 80% of children with Down syndrome are born to younger women simply because they have more babies than women over 35. The probability of women 35 to 39 years old giving birth to a Down syndrome baby is 1 in 214. When a woman is above 45 that probability increases to 1 in 19. (Huether, et al. [1998]."Maternal age specific risk rate estimates for Down syndrome among live births in whites and other races from Ohio and metropolitan Atlanta, 1970–1989". J Med Genet 35 [6]: 482–90.)

Down Syndrome Affects the Whole Person

Normally, humans have 46 chromosomes arranged in 23 pairs. The addition of an extra chromosome 21 in those living with Down syndrome causes a metabolic imbalance in the overall functioning of the human organism. This imbalance causes the characteristics that typify individuals with Down syndrome, including the common physical traits and various medical conditions that are the result of the extra chromosome. Individuals living with Down syndrome have a greater incidence of certain types of leukemia, cardiac and thyroid issues, vision and hearing problems, gastro-intestinal issues, and others. People usually think of intellectual disability associated with Down syndrome, but Down syndrome is not just a neurodevelopmental disability. It is also a neurodegenerative disability. Since the lifespan of individuals born with Down syndrome has increased significantly, more and more attention is being given to the physical and mental degenerative effects of living for over 60 years with an extra chromosome. 

Human Genetics and Human Variability

Chromosomes contain all the individual hereditary characteristics unique to each person. Those characteristics are encoded in the individual's DNA. The smallest unit of genetic information is called a gene, and there are numerous genes on each chromosome. It is thought that there are approximately 20,000 to 25,000 protein encoding genes contained on the entire human genome. Chromosome 21 is the smallest human chromosome, and it is thought that it contains at least 160 protein encoding genes.  

Each person with trisomy 21 is first of all the son or daughter of his or her parents  - a unique gift, and a unique human person. There is just as much human variability with regard to appearance, talents, potential, and capabilities in individuals with trisomy 21 as in those who possess the typical number of chromosomes. Just like every individual human person, those with Down syndrome have their own unique way of expressing this excess of genes contained on their extra 21st chromosome.

What allowed John Langdon Down to first describe Down syndrome are the characteristics common to all. The most notable characteristics is their intellectual disability and unique physical traits. But there are often congenital complications present at birth such as heart defects and digestive disorders; or in the course of life endocrine, orthopedic, visual, auditory issues, and other health issues. Most of these complications can be treated, and a well-qualified physician knows the importance of screening for them periodically.

The life expectancy of individuals with Down syndrome has significantly increased over the last few years. Trained medical professionals are well equipped to provide the best possible quality of life to these individuals throughout the lifespan, and research continues to investigate treatments to improve cognition, memory, and speech. Of particular urgent concern to researchers and parents is the universal development of Alzheimer’s disease in aging individuals with Down syndrome.

Types of Down Syndrome

There are different types of Down syndrome, the most common being trisomy 21 that is caused by a nondisjunction, or an error in division of the sperm or egg cells. Trisomy 21 representing approximately 95% of cases of trisomy 21.

In trisomy 21, the karyotype (the pattern of chromosomes) is written 47, XX , +21 if it is a girl, 47, XY, +21 if it is a boy. (notice 47 instead of 46, and +21 to indicate the additional 21st chromosome). The extra 21st chromosome is present in every cell of the individual's body.

Individuals with mosaic Down syndrome have cells with 47 chromosomes (three copies of chromosome 21) coexisting in certain cell lines in the body, while other cells have the typical 46 chromosomes. The proportion of two types of cells varies considerably from one subject to another, and in the same individual, from one organ or tissue to another.
The third type of Down syndrome is called a translocation The karyotype of these individuals shows 2 chromosomes 21 with the third being transposed or attached to another chromosome.
Contrary to what is often said, there are no degrees of trisomy 21. Again, those who have full trisomy 21 have an extra 21st chromosome in every cell of their body. The way this trisomy manifests itself from individual to individual remains unknown. 

We do not yet understand the reason for a nondisjunction resulting in trisomy 21.  In a small percentage of cases, there is a familial risk factor for a translocation of chromosome 21.

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