Genetics

Question 1

For BRCA 1 and 2, what are the lifetime risks of breast Ca, risk of breast Ca before 70, lifetime risk of ovarian Ca?

What is the lifetime risk of Breast Ca for women?

What is the lifetime risk of Ovarian Ca for women?

How many inherited breast cancers are BRCA 1/2?

How many people disgnosed with breast Ca will be BRCA 1 or 2?

Answer 1

General population breast Ca - 12%

General population Ovarian Ca 1.3%

BRCA 1

• Breast lifetime: 70%
• Ovarian lifetime - 40%

BRCA 2

• Breast lifetime: 45%
• Ovarian lifetime - 15%

25% of inherited breast Ca is BRCA 1/2

1 in 20 people with breast Ca will be BRCA1/2 positive

Question 2

Describe the pattern of:
- PAPP-A
- AFP
- Oestriol
- HCG
- Inhibin A

In Down’s syndrome and Edwards (trisomy 18)

Answer 2

Down’s
- Low PAPPA
- Low AFP
- Low Oestriol
- High HCG
- High Inhibin A

Edwards - LOW EVERYTHING

Question 3

What is high AFP associated with in screening? If everything else is normal

Answer 3

Neural tube defects!

Question 4

What is MSS1

Answer 4

HCG
PaPP-A
NT

Question 5

What is MSS2

Answer 5

HCG
Oestriol
Inhibin A
AFP

Question 6

How common is Down’s syndrome?

What are the test results?

Answer 6

1:1000

Low PAPP-A, low AFP, low oestriol, high HCG, high inhibin A

Question 7

How common is Edward’s?

What are the screening test results?

Answer 7

1:6000

Everything low

Question 8

How common is Patau’s?

Answer 8

1:15000

Question 9

What is congenital adrenal hyperplasia?

What is the cause in most cases?

What does this result in biochemically?

INHERITANCE?

Answer 9

You have a deficiency of enzymes that regulate the steroid hormones in the adrenals.

Most cases - deficiency of 21-hydroxylase. This results in excess androgens and deficiency in mineralocorticoids

AUTOSOMEAL RECESSIVE

Question 10

Describe the management of beta thalassaemia in pregnancy

Answer 10

At the start:
- Folic acid 3 months prior to conception
- Cardiology assessment
- Biliary USS and Liver fibro scan
- Dexa scan

Throughout with scans:
- Early scan 7-9 weeks
- Monthly biometry from 24 weeks

Thromboprophylaxis:
- If splenectomy + plt >600 - ASA and LMWH
- If splenectomy OR plt >600 - ASA

Question 11

What is the timing window for the combined test?

Answer 11

11+2 - 14+1

Question 12

HNPCC:
- Inheritance pattern
- Risks of colon Ca/endometrial Ca

Answer 12

AD

Colon - 80%
Endometial - 40%

Question 13

What is the karyotype for kleinfelters

Answer 13

47XXY

Question 14

TURNER’s SYNDROME

How common?

Features?

Biochemistry:

What percentage of turner’s baby’s will miscarry?

Answer 14

Karyotype - 45XO

1:2500 females

Features
- Webbed neck
- Wide spaced nipples
- Heart problems: most common is bicuspid aortic valve
- Primary amoennorhoea

Biochemistry: high FSH and LH at puberty

> 95% will miscarry. Approx only 1% survive

10-15% of further trimester losses are thought to be secondary to Turner’s

Question 15

When should the guthrie test be performed?

What does it test for?

Answer 15

After 12 hours following delivery

Loads of things:
Phenylketonuria
MCCAD
Maple syrup urine disease
congenital hypothyroidism
CF
Galactosaemia

Question 16

When is amnio performed?
When is CVS performed?

Answer 16

Amnio - preferred test after 15 weeks

CVS - Usually 10-12th week

Question 17

Phenylketonuria

How common is it?

Inheritance pattern of PKU1 ?

When do you do the test?

What is the treatment?

Answer 17

1:14000

Test after 12 hours following birth

PKU 1 - AR

High concentrations of phenylalanine lead to high conc of by products starting with phenyl

Treatment - restriction of phenylalanine

Question 18

What is the phenotype for XYY?

Answer 18

‘Normal’ male!