The Effects of Trisomy 21 - Symptoms of Down Syndrome

In trisomy 21, there is extra genetic material from chromosome 21. This extra material means that there are more genes expressed than normal. For most genes, this overexpression has little effect because the body regulates genes and their products. But the genes that cause Down syndrome appear to be exceptions.

Scientists have been trying to determine exactly which genes are involved in Down syndrome ever since the third 21st chromosome (trisomy 21) was found. Current research has led to a theory that only certain areas of chromosome 21 need to be tripled to get the effect of Down syndrome. These regions are called the Down syndrome critical region. Exactly which genes cause Down syndrome when tripled is not known, but some genes are suspected.

Genes that may have input into Down syndrome include:

• SOD1 (superoxide dismutase 1 gene) overexpression may cause premature aging and decreased function of the immune system.
  
  
• COL6A1 (alpha-1 collagen VI gene) overexpression may be the cause of heart defects.
  
  
• ETS2 (ETS2 oncogene) overexpression may be the cause of skeletal abnormalities.
  
  
• CAF1A (chromatin assembly factor 1, p60 subunit) overexpression may cause problems with DNA synthesis.
  
  
• CBS (cystathione beta synthase) overexpression may disrupt metabolism and DNA repair.
  
  
• DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1A) overexpression may be the cause of mental retardation.
  
  
• CRYA1 (alpha-1 crystallin) overexpression may be the cause of cataracts.
  
  
• GART (glycinamide ribonucleotide synthetase) overexpression may disrupt DNA synthesis and repair.
  
  
• IFNAR (interferon alpha receptor) overexpression may interfere with the immune system as well as other organ systems.

Remember that no gene has yet been fully linked to any feature associated with Down syndrome.

Figuring out which genes may be associated with Down syndrome is difficult because, although there are certain characteristics associated with Down syndrome, people with Down syndrome have a wide variety of features and a wide range of mental retardation and developmental delay is possible. Some babies are born with heart defects and others aren't. Some children have associated illnesses such as hypothyroidism, and others don't. There are some possible explanations for this variability.

Genes come in different versions (alleles). For example, one allele for eye color produces blue eyes and one allele produces brown eyes. The variety of features in Down syndrome may be related to which version (allele) of a gene is present in triplicate. Also, some alleles cause a condition in some people but not in others, which is called reduced or incomplete penetrance. Reduced penetrance appears to occur with trisomy 21: the extra alleles don't do the same thing to every person who has them. Both the type of allele and the penetrance of the allele may be why there is such variation in children and adults with Down syndrome.