Down Syndrome

Question 1

What kind of disorder is Down syndrome?

Answer 1

A genetic disorder caused by the presence of three copies of the 21st chromosome. (trisomy 21)

Question 2

Prevalence of DS?

Answer 2

16 per 10 000 babies and 35% of intellectual disabilities.

Question 3

Clinical presentation of DS?

Answer 3

-A spectrum.
-Nearly all DS patients have intellectual and physical disabilities.
-Poor immune function.
-Increased risk of other health conditions

Question 4

Neurological characteristics of DS?

Answer 4

• IQ ranges from 35-69
  -Speech abnormalities

Question 5

Comorbidities of DS?

Answer 5

-Mental illness occurs in 30% (autism in 5-10%)
-Epileptic seizures
-Dementia/Alzheimers

Question 6

Diagnosing DS?

Answer 6

Prenatal and clinical genetic testing:
1. Chorionic villus sampling (CVS)
2. Amniocentesis

Question 7

What is chorionic villus sampling?

Answer 7

Cells taken from the placenta are used to analyze fetal chromosomes.

Question 8

What is amniocentesis?

Answer 8

A sample of amniotic fluid surrounding the fetus is withdrawn through a needle inserted into the mother’s uterus.

Question 9

Trisomy 21?

Answer 9

-Overexpression of each of the 300-500 genes carried on chromosome 21.
-Extra chromosome occurs by chance.

Question 10

What is the most significant risk factor for trisomy 21?

Answer 10

Advanced maternal age.

Question 11

Mosaic DS?

Answer 11

This occurs in a very small percentage of cases. Some of the cells in the body are normal, while others have trisomy 21.

Question 12

What causes Trisomy 21?

Answer 12

Failure of the 21st chromosome to separate during egg or sperm development. Sperm or egg cells are produced with an extra copy of chromosome 21.

Question 13

What is the percentage of cases caused by failure to separate?

Answer 13

88% of cases of trisomy 21 result from the nonseparation of the chromosomes in the mother, 8% result from the nonseparation of the chromosomes in the father, and 3% after the egg and sperm have merged.

Question 14

Why does an extra copy of the 21 chromosomes cause a problem?

Answer 14

Extra genetic material leads to overexpression of genes.

Question 15

What genes are overexpressed?

Answer 15

Some research suggests that genes for beta-amyloid and superoxide dismutase (SOD) are overexpressed.

Question 16

What is associated with dementia-like symptoms in both Alzheimer’s and DS patients?

Answer 16

Beta-amyloid overproduction.

Question 17

What is beta-amyloid?

Answer 17

Beta-amyloid is a protein derived from the amyloid precursor protein (APP), located on Chromosome 21 and is the main component of amyloid plaques.

Question 18

How does this cause dementia-like symptoms?

Answer 18

Beta-amyloid builds up and clogs synapses.

Question 19

What is oxidative stress?

Answer 19

The imbalance between the production and removal of oxygen-derived free radicals.

Question 20

What does oxidative stress contribute to?

Answer 20

1. Decreased immune function (lipid peroxidation)
2. Premature aging (DNA oxidation)
3. Impaired mental function (Protein oxidation)

Question 21

What gene plays a role in oxidative stress?

Answer 21

The gene for superoxide dismutase is located on chromosome 21, and it’s activity seems to be increased in DS patients.

Question 22

What does the hyperactivity of the superoxide dismutase cause?

Answer 22

It produces hydrogen peroxide (less harmful than –O2).

Question 23

But why is superoxide dismutase bad?

Answer 23

The presence of ferrous iron (Fe2+), and hydrogen peroxide forms the highly toxic hydroxyl radical (OH), which can result in profound cellular damage.

Question 24

What do DS patients show?

Answer 24

DS patients typically show deficits in iron transport across membranes and are therefore at risk of experiencing oxidative stress.

Question 25

How does the extra chromosome affect this?

Answer 25

Because of the extra chromosome, they have higher production of beta-amyloid and SOD.

Question 26

Managing DS?

Answer 26

There is no cure. Only management like education and proper care. Supplementation with antioxidant nutrients has been a potential therapy.