Clinical Assessment of Patients & Screening

Question 1

What is hypertelorism? [1]

Answer 1

when the pupils are too far apart

Question 2

What is distinctive about the philtrum in fetal alcohol syndrome?

Answer 2

the philtrum is smooth

Question 3

What is syndactyly? [1]

Answer 3

fingers/toes are joined up

Question 4

What is polydactyly? [1]

Answer 4

increased number of fingers/toes

Question 5

What is polysyndactyly? [1]

Answer 5

too many and joined up fingers/toes

Question 6

Name 2 dysmorphic features seen in Velocardiofacial Syndrome [2]

Answer 6

1. prominent nose
2. upslanting palpebral fissures

Question 7

Name 4 dysmorphic features seen in Rubinstein-Taybi Syndrome [4]

Answer 7

1. downslanting palpebral fissures
2. microcephaly
3. broad thumbs
4. big toes

Question 8

Pre-Implantation Diagnosis (PGD)

1. definition? [1]
2. what are the 2 methods of embryo biopsy? [2]
3. types of genetic screening tests used? [2]
4. pros of PGD [2]
5. cons of PGD [4]

Answer 8

1. checking the genes or chromosomes of the embryos for a specific genetic conditon
2. biopsy methods:
   
   • taken at 3 days when the embryo has 6-10 cells or
   • taken at 5-6 days when the embryo has approx. 100 cells
3. types of genetic screening tests used:
   
   • QF-PCR or
   • FISH
4. pros of PGD:
   
   • permits implantation of unaffected embryo
   • termination of pregnancy then unnecessary
5. cons of PGD:
   
   • possible long wait
   • not available to all women due to it being an IVF procedure
     
     • (may restrict by age or by AMH level as an indicator of no. of remaining follicles)
   • difficulty with multiple visits or procedures
   • take home baby rate is about 30-50%

Question 9

List the main principles of a screening programme [10]

Answer 9

1. the condition should be an important health problem
2. the natural history of the condition should be well understood
3. there should be a detectable early stage
4. there should be a benefit to treatment at an early stage
5. a suitable test should be devised for the early stage
6. the test should be acceptable
7. intervals for repeating the test should be determined
8. adequate health service provision should be made for the extra clinical workload resulting from screening
9. the benefits should outweight the risks, both physical and psychological
10. the costs should be balanced against the benefits

Question 10

What is sensitivity and how is it calculated? [2]

Answer 10

1. % of affected people who tested positively
2. = true positive/(TP+FN)

Question 11

What is specificity and how is it calculated? [2]

Answer 11

1. % of unaffected people who tested negatively
2. = true negative/(FP+TN)

Question 12

Describe prenatal screening tests used to screen for Down’s Syndrome [2]

Answer 12

1. combined ultrasound (nuchal transluency) and biochemical screening test (CUBS) (maternal blood biochemical markers)
2. nuchal transluency is increased in Down’s

Question 13

Name the 3 neonatal screening tests and which conditions each are used to screen for [3]

Answer 13

1. mass spectrometry
   
   • used to detect phenylketonuria and MCADD
2. immunoassay
   
   • used to detect congenital hyperthyroidism and cystic fibrosis
3. HPLC
   
   • used to detect sickle cell disease

Question 14

List 3 features of chorionic villous sampling [3]

Answer 14

1. occurs at 10-12 weeks (1st trimester)
2. up to 1/50 miscarriage rate
3. result given in less than a week

Question 15

List 4 features of amniocentesis [4]

Answer 15

1. occurs at 16-18 weeks (2nd trimester)
2. up to 1/100 miscarriage rate
3. result given in 1-2 weeks
4. difficulty if mother wants to terminate pregnancy after test results

Question 16

Under what circumstances are genetic diagnostic tests carried out? [4]

Answer 16

these tests are done when:

1. individuals have a high genetic risk
2. need for high sensitivity and specificity test
3. positive screening test
4. there is family history

Question 17

How does Non-Invasive Prenatal Diagnosis (NIPD) work and what is it used to detect? [3]

Answer 17

1. detection of free fetal DNA in maternal serum
2. can be used to detect:
   
   • male pregnancies (for x-linked recessive condition) or
   • to detect father’s mutation