Down's Syndrome Biochemical Screening - Part 1

Question 1

What genetic malfunction is the cause of about 95% of cases of Down Syndrome? What causes the remainder of cases?

Answer 1

• 95% of regular T21 is due to non-disjunction - 85% is maternally derived, 15% is paternally derived.
• 4% due to translocation (usually Robertsonian).
• 1% Mosaicism.

Question 2

Describe the clinical features of Downs Syndrome.

Answer 2

• Classically described appearance.
• Developmental delay and learning difficulties - spectrum.
• 4-50% congenital heart defects.
• 45% Alzheimers from 45 years.
• Others: Hearing and opthalmic problems, Musculoskeletal, GI, thyroid, Leukaemia risk.

Question 3

Outline how Downs Syndrome has developed in the UK.

Answer 3

• In Nottingham screening was started in 1991. They had previously been running a test looking at neural tube defects and this was related because you are looking at 1 particular serum marker in the maternal blood for affected pregnancies.
• The Trent region were funded to run a regional programme to study different marker combinations and establish which combinations to adopt as a region. This was regional not national.
• Practices and customs evolved locally. There were no national guidelines, were largely doing what local consultants etc. were interested in doing and some of them didn’t want to do Down syndrome screening at all. There was some local resistance initially.
• There were a lot of differences in clinical practice between what clinicians were doing, what labs were after etc. DS screening was essentially put together from a patchwork of different practises and is still evolving.
• Different demands on the UK labs.

Question 4

Outline how the National DS screening programme developed.

Answer 4

• In April 2001 the Minister for Public Health said in the House of Commons that there would be a screening programme for DS available to pregnant women if they want it - came as a bit of a surprise to the NHS as the NHS was not even aware of who was and who was not being offered DS screening in different regions.
• Commitment to equality of access.
• Review of services nationally - a lot of behind the scenes work occurred to work out what was actually in place at that moment in time and then a gap analysis to figure out how to roll out a national programme.
• Now wrapped up in the NSC FASP.
• Model of Best Practice and Performance Standards.

Question 5

What is screening?

Answer 5

‘Screening is a public health service in which members of a defined population, who do not necessarily perceive they are at risk of, or are already affected by a disease or its complications, are asked a question of offered a test to identify those individuals who are more likely to be helped than harmed by further tests or treatments to reduce the risk of a disease or its complications.’

• Screening is simply dividing up the population into 2 groups of those who are or are not going to go forward for a definitive diagnostic test.
• Screening tests aim to identify those individuals who will go on to further tests.
• Only to divide population up into two groups.
• Then consider diagnostic tests or treatments.
• Limitations not widely understood.

Question 6

How would you calculate the detection rate for a screening programme?

Answer 6

Detection Rate = Number of true positives detected / Number of positives actually present (affected pregnancies)

Question 7

How would you calculate the screen positive rate for a screening programme?

Answer 7

Screen positive rate = Number in the high chance group (i.e. positive) / Total number screened

Question 8

How would you calculate the false negative rate for a screening programme?

Answer 8

False negative rate = number in the low chance group who are actually affected / total number being screened.

Question 9

Outline some of the terminology used when discussing screening programmes.

Answer 9

• Uptake Rate = people who have been approached from the defined population who actually take up the test.
• Affected population
• Unaffected population
• Detection rate = Number of true positives detected / Number of positives actually present (affected pregnancies)
• Screen positive rate = Number in the high chance group (i.e. positive) / Total number screened
• False negative rate = number in the low chance group who are actually affected / total number being screened.