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Semester 5 November > Genetics > Flashcards

Flashcards in Genetics Deck (33)
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Big 5 genetic defects

Congenital heart disease
NTDs
Hemoglobin disorders
Down's syndrome
G6PD deficiency

1

What does genetic risk increase with

Number of affected fam members
Frequency in population

2

Types of genes affected in NTDs

Folate metabolism ( not SA)
Other metabolic genes
Genes related to neural tube development (planar cell polarization pathway)
Neural plate bending (SHH)
Epigenetic

3

'Syndromic' NTD conditions

Downs
Triploidy

Meckel gruber (AR)
Curriano syndrome (AD)

4

Environmental factors in NTDs

Seasonal variation
Geographic variation
Nutritional
Twins
Teratogens (alcohol, anticonvulsant, hyperthermia)

5

Prenatal diagnosis of NTD

U/S
AFP
Maternal serum screen
Second trimester aneuploidy screening
Amnio = very rare

6

Congenital defect in platelet function

Von Willebrand disease (AD)

7

X linked recessive bleeding disorder

Haemophillia A or B

8

Why may females bleed in haemophilia

One X eg Turners syndrome
Both copies of gene
Skewered X inactivation pattern
Other X abnormalities

9

Congenital thrombosing disorders

Antithrombin 3 deficiency
Protein C and S def
Factor V Leiden
Prothrombin mutation

All autosomal dominant but reduced penetrance

10

Aetiology of NTDs

Isolated (familiality + environmental factors)
Spectrum of disorders (commonly meningomyelocoele and anencephaly)

11

Teratogens in NTD

Maternal IDDM
Anticonvulsants (valproate/ carbamazepine)
Alcohol
Hyperthermia

12

Outcome in prenatal diagnosis of NTD depends on..

Type and level of lesion
Associated findings
Post natal course (hydrocephalus / shunt complications)

13

Primary prevention of NTDs

Improve health, nutrition
Family planning
Rx chronic diseases eg DM, epilepsy
Avoid teratogens
Genetic counseling
PRECONSEPTUAL FOLATE

14

Folic acid doses

1 month before preg to 3 months after birth

400ug ''normal risk''
4mg previous NTD, affected parent, 2nd degree relative

15

Secondary prevention of NTDs

Identify woman at risk
U/S
Genetic counseling
Voluntary antenatal testing (if appropriate)
Access to voluntary TOP

16

Tertiary prevention of NTDs

Early/ accurate diagnosis
Intervention to avoid/ minimize complications
Medical/ surgical Rx
Rehab therapy
Psychosocial support

17

Congenital bleeding disorders

Rare AR deficiencies (eg factor Xl def - Ashkenazi Jews)(prothrombin/fibrinogen defs)
X linked recessive - Haemophilia
Congenital platelet defects - Von Willebrand Disease

18

Clinical presentation of haemophilia

Spontaneous bleeds into joints/muscles
Excessive bleeding after trauma or surgery

19

Management of haemophilia

Factor replacement (acute vs prophylactic)
Monitor for inhibitors
Supportive therapy eg physio
Genetic counseling

20

Problems with gene based therapy

Getting to target
Site of insertion
Effects of vector NB immune
Expression (how much, when, how long, control)
Timing of replacement

21

Why is gene therapy for haemophilia possibly possible

Small gene
Single target organ (liver)
Only small amount of clotting factor needed
Continuous production of factor
No effects on development

22

Haemophilia A is a def in..

Factor Vlll

23

Haemophilia B is a def in

Factor lX

24

Clinical presentation of thrombosing disorders

Venous thrombosis/ embolism
Pregnancy loss

25

When is a genetic disorder more likely in thrombosis

Young
No precipitant
Unusual site
Recurrent
Family history

26

Management of thrombosis

Anticoagulation
Avoid risk factors eg COC
Genetic counseling

27

What is Factor V Leiden

Substitution of amino acid (from A/G sub)
Abnormal factor V. Resistance to activated protein C. Less control over thrombin production.

28

Who do we test for low penetrance common mutations causing thrombosis

First unprovoked VTE
Recurrent VTE
Thrombosis in unusual sites (cerebral, mesenteric, portal, hepatic)
VTE in pregnancy
VTE associated with COC and HRT
FDR with VTE under 50yrs

29

Things to take into consideration in genetic counseling

- age
- parity
- social/cultural background
- religion
- support
- finances
- previous experience with disability