Ethical Issues

Limitations of Genetic Testing
Some genetic tests do not identify all of the possible gene mutations that can cause a particular condition. The test may subsequently require difficult decisions without providing full information.
Genetic testing is unable to provide a definite result or an indication of severity of the condition.
E.g. If both parents are carriers of the CF gene. prenatal diagnosis can be performed to determine whether a foetus has inherited a CF gene mutation from each parent. Knowing that a foetus has inherited 2 CF mutations, however, does not, at this time, predict the severity of CF in the baby.

Should the Information Be Obtained if No Treatment or Intervention Exists?

Undesired Options After Genetic Testing
a positive prenatal test result creates additional decisions for women and couples, including consideration of invasive testing, such as amniocentesis, and the possibility of pregnancy termination.
Ethically, a dilemma may present if that the couple should not wish to make such decisions

False-Positive and False-Negative Results
Multiple marker screening detects about 80% of pregnancies in which an open neural tube defect is present and about 60% of pregnancies in which Down syndrome is present.
Most women who receive false-positive results have normal pregnancy outcomes; however, these results often lead to further diagnostic testing, leading to increased anxiety about possible outcomes including pregnancy termination.
Based on the outcomes of these tests parents may make the decision to terminate, or not to terminate.

Potential Adverse Personal or Societal Consequences
Persons who qualify for genetic testing may believe it is more difficult to obtain insurance because of the testing or are afraid to change jobs because of fear of losing health insurance.
Some persons at risk for HD have been reluctant to discuss genetic testing with their health care provider because of fears that this information may be revealed to their health insurance carrier.

screening tests

Screening tests are available to all pregnant women. They are non-invasive and carry no risk of miscarriage. Screening tests can involve a maternal serum screening and/or an ultrasound.

Ultrasound involves using sound waves to take a picture of the foetus. Gel is spread over the lower abdomen of the pregnant woman and then a transducer (a metal instrument) is moved over the skin. The sound waves are analysed by a computer to give a scan that can be viewed on a television. This process is painless and there are no known hazards. During an ultrasound, a foetus can be detected as having Downs Syndrome if “nuchal translucency” is seen – a thickening of skin over the neck.

There are two ideal times for an ultrasound:
1st Trimester ultrasound – nuchal ultrasound at 11-13 weeks
2nd Trimester ultrasound – (also called foetal anomaly scan) 18-20 weeks, identifies structural problems, but does not detect all abnormalities

Maternal serum screening is a blood test which can identify pregnant women who are at an “increased risk” of having a child with Downs Syndrome (this test can also be used for neural tube defects and Trisomy 18). A blood sample is taken from the mother and the amounts of hormone and foetal protein are measured. Mothers with foetuses that have Downs Syndrome have abnormal amounts of these proteins compared to mothers with unaffected pregnancies.

Two maternal screening tests are available in Victoria – the mother can have one or the other, but not both:
1st Trimester combined screening: a blood test done at 9-12 weeks (best at 10 weeks) combined with a nuchal translucency ultrasound scan at 11-13 weeks
2nd Trimester maternal serum screening: a blood test at 14-20 weeks

Maternal serum screening tests can detect 60% of foetuses with Downs Syndrome; however, when combined with an ultrasound at 11-13 weeks into the pregnancy, the sensitivity increases to about 90% with a 5% false-positive rate. Nevertheless, positive tests from screening tests are not definitive enough to diagnose Downs Syndrome – further procedures/tests will be required such as amniocentesis.

Life expectancy of for people with Downs Syndrome has improved in the last 40 years (from an average of 16years to 57.8 years for women and 61.1 years for men). Current estimates for life expectancy of a person with Downs Syndrome vary from 30-40 years, although children who survive infancy are expected to live longer than this (2006).

Clinical Features of Down's Syndrome

Oblique eye fissures with epicanthic skin folds on the inner corner of the eyes, muscle hypotonia (poor muscle tone), a flat nasal bridge, a single palmar fold, a protruding tongue (due to small oral cavity, and an enlarged tongue near the tonsils), a short neck, white spots on the iris known as Brushfield spots,[3] excessive joint laxity including atlanto-axial instability, congenital heart defects, excessive space between large toe and second toe, a single flexion furrow of the fifth finger, and a higher number of ulnar loop dermatoglyphs. In addition, individuals with Down syndrome can have serious abnormalities affecting any body system. They also may have a broad head and a very round face.

Genetic Basis

Down syndrome is a chromosomal abnormality characterized by the presence of an extra copy of genetic material on the 21st chromosome, either in whole (trisomy 21) or part (such as due to translocations). The effects of the extra copy vary greatly among people, depending on the extent of the extra copy, genetic history, and pure chance. The extra chromosomal material can come about in several distinct ways. A typical human karyotype is designated as 46,XX or 46,XY, indicating 46 chromosomes with an XX arrangement typical of females and 46 chromosomes with an XY arrangement typical of males.

Types of Down Syndrome

Trisomy 21
Trisomy 21 (47,XX,+21) is caused by a meiotic nondisjunction event. With nondisjunction, a gamete (i.e., a sperm or egg cell) is produced with an extra copy of chromosome 21; the gamete thus has 24 chromosomes. When combined with a normal gamete from the other parent, the embryo now has 47 chromosomes, with three copies of chromosome 21. Trisomy 21 is the cause of approximately 95% of observed Down syndromes, with 88% coming from nondisjunction in the maternal gamete and 8% coming from nondisjunction in the paternal gamete.

Mosaicism

Trisomy 21 is caused prior to conception, and all cells in the body are affected. However, when some of the cells in the body are normal and other cells have trisomy 21, it is called Mosaic Down syndrome (46,XX/47,XX,+21). This can occur in one of two ways: A nondisjunction event during an early cell division in a normal embryo leads to a fraction of the cells with trisomy 21; or a Down syndrome embryo undergoes nondisjunction and some of the cells in the embryo revert to the normal chromosomal arrangement. There is considerable variability in the fraction of trisomy 21, both as a whole and among tissues. This is the cause of 1–2% of the observed Down syndromes.

Robertsonian translocation

The extra chromosome 21 material that causes Down syndrome may be due to a Robertsonian translocation. In this case, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14 (45,XX, t(14;21q)) or itself (called an isochromosome, 45,XX, t(21q;21q)). These parents are phenotypically normal. Normal disjunctions leading to gametes have a significant chance of creating a gamete with an extra chromosome 21, producing a child with Down syndrome. Translocation Down syndrome is often referred to as familial Down syndrome. It is the cause of 2–3% of observed cases of Down syndrome.[9] It does not show the maternal age effect, and is just as likely to have come from fathers as mothers.

Duplication of a portion of chromosome 21

Rarely, a region of chromosome 21 will undergo a duplication event. This will lead to extra copies of some, but not all, of the genes on chromosome 21 (46,XX, dup(21q)). If the duplicated region has genes that are responsible for Down syndrome physical and mental characteristics, such individuals will show those characteristics. This cause is very rare and no rate estimates are available.

Screening Tests for Downs Syndrome

Screening tests are available to all pregnant women, are non-invasive and carry no risk of miscarriage. Screening tests can involve a maternal serum screening and/or an ultrasound.

Ultrasound involves using sound waves to take a picture of the foetus. Gel is spread over the lower abdomen of the pregnant woman and then a transducer (a metal instrument) is moved over the skin. The sound waves are analysed by a computer to give a scan that can be viewed on a television. This process is painless and there are no known hazards. During an ultrasound, a foetus can be detected as having Downs Syndrome if “nuchal translucency” is seen – a thickening of skin over the neck.

There are two ideal times for an ultrasound:

• 1^st Trimester ultrasound – nuchal ultrasound at 11-13 weeks
• 2^nd Trimester ultrasound – (also called foetal anomaly scan) 18-20 weeks, identifies structural problems, but does not detect all abnormalities

Maternal serum screening is a blood test which can identify pregnant women who are at an “increased risk” of having a child with Downs Syndrome (this test can also be used for neural tube defects and Trisomy 18). A blood sample is taken from the mother and the amounts of hormone and foetal protein are measured. Mothers with foetuses that have Downs Syndrome have abnormal amounts of these proteins compared to mothers with unaffected pregnancies.

Two maternal screening tests are available in Victoria – the mother can have one or the other, but not both:

• 1^st Trimester combined screening: a blood test done at 9-12 weeks (best at 10 weeks) combined with a nuchal translucency ultrasound scan at 11-13 weeks
• 2^nd Trimester maternal serum screening: a blood test at 14-20 weeks

Maternal serum screening tests can detect 60% of foetuses with Downs Syndrome; however, when combined with an ultrasound at 11-13 weeks into the pregnancy, the sensitivity increases to about 90% with a 5% false-positive rate. Nevertheless, positive tests from screening tests are not definitive enough to diagnose Downs Syndrome – further procedures/tests will be required such as amniocentesis.

Life expectancy of for people with Downs Syndrome has improved in the last 40 years (from an average of 16years to 57.8 years for women and 61.1 years for men). Current estimates for life expectancy of a person with Downs Syndrome vary from 30-40 years, although children who survive infancy are expected to live longer than this (2006).