Brain Primer

Understanding Down Syndrome

  • Reviewed27 Mar 2023
  • Author Karen Weintraub
  • Source BrainFacts/SfN
Child with down syndrome playing a game via SDI Productions

Down syndrome is named for the English physician who first described it in 1866, but nearly 100 years passed before scientists determined what caused the condition: possessing an extra copy of all or part of the 21st chromosome.

People with this syndrome have three copies of this genetic material, instead of two. In some cases, the extra copy, or trisomy, does not occur in every cell, producing what’s known as mosaicism. *Around 6,000 babies are born each year with Down syndrome in the United States, with the condition occurring in about one in every 700 births.
There is no clear cause of the genetic condition, although maternal age is a major risk factor for Down syndrome. Women who become pregnant at 35 and older are more likely to have a pregnancy affected by Down syndrome when compared to women who become pregnant at a younger age.

Since late 2011, fetuses can be screened for Down syndrome using the mother’s blood. In the past, the risk of test procedures meant that only older mothers (whose likelihood of having a Down syndrome child was known to be higher) should be screened. Younger mothers didn’t know until delivery whether their child would have Down syndrome. The blood test, unlike other more invasive prenatal checks for birth defects and genetic abnormalities like amniocentesis and chorionic villus sampling, poses no risk to the baby, so it can also be used for younger mothers whose chance of having a child with Down syndrome is quite small.

Children born with Down syndrome have distinctive facial features, including a flattened face and bridge of the nose, eyes that slant upward, and small ears. They usually have small hands and feet, short stature, and poor muscle tone as well. The intellectual abilities of people with Down syndrome are typically low to moderate, although some people graduate from high school and college, and many successfully hold jobs. Other symptoms of Down syndrome can include hearing loss and heart defects, and virtually everyone born with Down syndrome will develop early-onset Alzheimer’s disease, often in their 40s or 50s. Chromosome 21 contains the gene that encodes amyloid precursor protein (APP), an Alzheimer’s disease risk factor, and possessing an extra copy of this gene might cause the early onset of the disease. Interestingly, people with mosaic Down syndrome seem to have milder symptoms and are more likely to live past 50.

There is no real treatment for Down syndrome, nor any clear explanation of what occurs in the brain. Poor connections among nerve cells in the hippocampus, the part of the brain involved in memory (and the first brain area affected by Alzheimer’s disease), are believed to be a key factor in brain or intellectual differences in Down syndrome. Dysfunction in the mitochondria, the cell’s power plants, might also play a role in development of related disorders that involve energy metabolism, such as diabetes.

Scientists have grown stem cells from fetuses with Down syndrome and used them to test potential treatments and confirm which molecular pathways are involved in the condition. In one such laboratory study, researchers took a gene that typically inactivates the second X chromosome in female mammals and spliced it into a stem cell that had three copies of chromosome 21. In these cells, the inactivation gene muted the expression of genes on the extra chromosome 21, believed to contribute to Down syndrome. Although this is a long way from any clinical applications, the model is being used to test the changes and cellular problems that occur with the tripling of the 21st chromosome, in hopes of eventually finding a treatment.

Adapted from the 8th edition of Brain Facts by Karen Weintraub.

*This statistic was updated March 27, 2023, to reflect the most recent CDC data on Down syndrome prevalence.



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