Down Syndrome: Genetic Causes, Risk Factors, and Prevention

Each year, the global Down syndrome community comes together to share ideas, experience, and knowledge, empowering each other to make a positive change in the world as part of World Down Syndrome Day. This year’s occasion took place on March 21, uniquely themed around connecting and creating an inclusive society based on equal opportunities, rights, and roles. 

To address the needs of members of the Down syndrome community in each of the territories, it has become imperative to better understand the condition, and the underlying genetic causes and risk factors. Down syndrome, formerly known as “Mongolism”, is a genetic disorder caused by the presence of an extra copy of chromosome 21 (trisomy 21). Clinically, the syndrome is characterized by growth retardation, varying degrees of intellectual disability, and craniofacial abnormalities, among others. 

The condition is mainly triggered by a genetic process at the onset of a human’s life cycle. Human somatic cells are diploid and contain 23 pairs of chromosomes (total number of chromosomes: 46). One chromosome in each pair comes from the father, the second from the mother. Gametes (sperm or egg cells) are haploid and have half-genomic content of somatic cells. When a somatic cell divides to produce gametes, homologous chromosomes form pairs, exchange genetic information, before they separate so that each daughter cell receives one member of each pair. Sometimes, however, chromosomes fail to detach during the first or the second meiotic division, and one cell receives 24 chromosomes whereas the second receives 22. When a gamete of 24 chromosomes (2 copies of 21) is involved in fertilization, the baby has trisomy 21.

This chromosomal abnormality accounts for 95% of cases. 

Down syndrome can also occur when chromosome 21 is translocated (attached) onto another chromosome before or at conception. These children have the usual two copies of chromosome 21 in addition to the translocated one. They are trisomic, yet they have a total number of 46 chromosomes. Their germ cells can achieve meiosis, and therefore, this structural abnormality can be inherited. It is referred to as familial trisomy 21 and accounts for 4% of Down syndrome cases.

The final 1% of Down syndrome cases is caused by somatic mosaicism produced by trisomic conception followed by loss of the extra copy of chromosome 21 during mitotic divisions of the fertilized egg. Children with mosaicism display different arrays of Down syndrome symptoms according to the proportion and localization of trisomic cells.   

Further to the genetic processes behind this condition, some parents have a higher risk of having offspring with Down syndrome. The age of the mother plays a significant role in increasing the underlying risks. The prevalence of Down syndrome is 1 in 2,000 births for women under 25 years of age. It increases with the age of the mother reaching 1 in 300 at 35 years and 1 in 100 at 40 years. Parents who have an affected child or a family history of trisomy 21 are at high risk of having babies with Down syndrome. 

There are now ways to treat Down Syndrome, but it is possible to prevent the condition. Parents should consult a genetic counselor who can evaluate the risk before conception and propose prenatal screening tests at the early stages of fetal development. More invasive tests, such as amniocentesis or chorionic villus sampling, are needed to determine the karyotype of the fetus and ascertain the diagnosis.

Children with Down syndrome require special care to prevent over-handicap. They must have regular medical follow-ups as they complain less and cannot always identify and express pain or a physical problem. Session of speech therapy, psychomotricity, or physiotherapy can compensate for developmental delays and lack of muscle tone. To be effective, these sessions must begin in the first year of life. Many children can go to normal schools when they have adapted inclusive education units such as small classes of 5 to 10 children with cognitive delays. Few can attend regular classes when they have sufficient cognitive abilities and if helped properly, they can grow and progress in an ordinary environment. 

In adulthood, some patients manage to develop independence. More than half of those affected may be able to work and live on their own. Examples of success stories include Marian Avila, a Spanish top model who has a flourishing career in the fashion world; and the Belgian actor Pascal Duquenne, who won the best actor award of the Cannes Film Festival in 1996 for his role of Georges, a boy with the same disability.