Obstetric genetics

Question 1

Define autosomal dominant

Answer 1

Heterozygotes with one copy of the abnormal gene atr affected

Question 2

Define autosomal recessive

Answer 2

Homozygotes with two copies of the abnormal gene are affected

Question 3

Define X-linked recessive

Answer 3

Males with one copy of the abnormal gene on the X-chromosome are affected

Question 4

Features of X-linked recessive inheritance

Answer 4

No male-male transmission
Unaffected carrier females
All men who inherit the mutation are affected

Question 5

Examples of common x-linked recessive disorders

Answer 5

Duchenne muscular dystrophy
Haemophilia
Red-green colour blindness

Question 6

Duchenne muscular dystrophy

Answer 6

Most common and severe form of muscular dystrophy
Presentation at 3-5 years
1/3 have learning difficulties as well
Waddling gait
Difficulty running/climbing stairs
Gradual deterioration leading to loss of mobility
Cardiorespiratory failure eventually

Question 7

Features of autosomal recessive inheritance

Answer 7

To develop diseases, both germ line mutations must be inherited
Equally transmitted by males and females

Question 8

Common autosomal recessive disorders

Answer 8

Hereditary haemochromatosis
Cystic fibrosis
B-thalassaemia

Question 9

Cystic fibrosis - symptoms

Answer 9

Progressive lung disease
Pancreatic dysfunction
Elevated sweat electrolytes

Question 10

For a recessive condition with early onset, what is the chance of a patient being a carrier if they are unaffected but their sibling is

Answer 10

2/3

Question 11

Assumptions of hardy-Weinberg principle

Answer 11

Large randomly mating population
Relative proportion of different genotypes remains Constant
No outside influences
2 alleles for an autosomal condition

Question 12

what is the hardy Weinberg equation ?

Answer 12

Question 13

What types of conditions is the hardy-Weinberg principle used for ?

Answer 13

Autosomal recessive and X-linked

Question 14

What factors can disturb the hardy Weinberg principle

Answer 14

Non-random mating

consanguinity - relationships between close relative can increase carrier risk within a family

high mutation rate can affect the mutation-selection eqm

selection of geterozygote advantage

Question 15

Describe the ultrasound scans given as routine prenatal screening

Answer 15

Dating scan at 8+ weeks

• identifies whether pregnancy is singleton/multiple

unchallenged translucency (NT) scan at 10-14 weeks :

• thickness of neural tube measured

feral anomaly scan at 18-20 weeks :

Question 16

Causes of increased neural tube thickness

Answer 16

Down syndrome

major congenital heart disease

skeletal dysplasias

diaphragmatic hernias

Question 17

Describe the biochemical serum screening tests

Answer 17

First trimester:

• 10-14 weeks gestation (done at same time at NT scan)
• accuracy dating needed to interpret results
• free beta-human chorionic gonadotropin , placenta-associated plasma protein A assessed
• high detection rate but needs sample from placenta or amniotic fluid

second trimester if women book later in pregnancy :

• alpha-feta protein
• free beta-HCG
• estriol

Question 18

What conditions does an abnormal MSAFP assay indicate?

Answer 18

>>MSAFP levels = neural tube defect / anterior ab wall defect / risk of miscarriage / lack of growth / multiple pregnancy / congenital nephrotic syndrome

Question 19

Name the non-invasive targeted tests

Answer 19

Ultrasound scans - surveillance/3D scans/feral echocardiogram

foetal MRI scan

molecular testing of foetal cells or DNA in maternal blood

Question 20

Invasive targeted test

Answer 20

Chorionic villus sampling (placental sampling)

• usually carried out at 11-13 weeks
• transabdominal approach
• yields foetal DNA for molecular tests

amniocentesis (sampling of amniotic fluid):

• usually carried out at 15-16 weeks
• analysis takes several weeks ; low yield of foetal DNA

cardocentesis (foetal blood sampling )

foetal tissue biopsy - liver, muscle, skin

Question 21

Polygenic inheritance

Answer 21

Inheritance controlled by many genes with small additive effects

genes at many different loci contribute to the phenotype

no gene is dom/rec

gradation of phenotypes

Question 22

Multifactorial inheritance

Answer 22

Risk is higher if a child of the lower risk gender is affected

even when someone has a high genetic liability they will not be affected if the environment is favourable

Question 23

Common congenital malformations

Answer 23

Cleft lip and palate

congenital dislocation of the hip

congenital heart defects

talipes (clubbed foot)

pyloric stenosis (obstruction of opening to the small intestine)

Question 24

Adult onset disorders with multifactorial inheritance

Answer 24

Diabetes Mellitus (type 1)

epilepsy

glaucoma

ischaemia heart disease

rheumatoid arthritis