Obstetric Genetics

Question 1

Why do patients come to an obstetric genetics clinic?

Answer 1

Have a family history and want info about risks to pregnancy;
Have abnormalities detected on scan- is this a genetic condition?;
Have abnormalities detected on a prenatal test - amniocentesis or CVS

Question 2

Autosomal dominant

Answer 2

Heterozygous with one copy of the abnormal gene affected

Question 3

Autosomal recessive

Answer 3

Homozygous with 2 copies of the abnormal gene are affected;
Equally transmitted by males and females;
Inherit 2 Germline mutations, one from each parent to develop the disease;

Question 4

X-linked recessive

Answer 4

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

Question 5

X-linked recessive inheritance

Answer 5

No male to male transmissions;
Female carriers are unaffected;
All men who inherit mutation are affected;
Appears to skip individuals;

Question 6

Common X linked recessive disorders

Answer 6

Duchenne muscular dystrophy;
Becker muscular dystrophy;
Haemophilia;
Red-green colour blindness;

Question 7

Duchenne muscular dystrophy

Answer 7

Most common and severe form of MD;
3-5 years;
Mild-moderate learning difficulties;
Waddling gait, positive Gower sign - difficulty rising from the floor, achieved by ‘climbing up the legs’;
Difficulty running and climbing stairs;
Gradual deterioration - loss of mobility, wheelchair bound;
Progressive muscle weakness;

Question 8

Common autosomal recessive disorders

Answer 8

Cystic fibrosis;

Hereditary haemochromatosis;

Question 9

Cystic fibrosis

Answer 9

1 in 2000;
Carrier freq: 1 in 25;
Autosomal recessive;
Progressive lung disease, pancreatic dysfunction, elevated sweat electrolytes;
Affects - respiratory tract, exocrine pancreas, intestine, male genital tract - complex multisystem disease

Question 10

Prenatal testing

Answer 10

Any test done in the anenatal period for the diagnosis of fetal disease;

Question 11

Types of prenatal tests

Answer 11

Morphological/Structural - ultrasound;
Biochemical - maternal or fetal;
Cytogenetic - karyotype;
Molecular genetic - cystic fibrosis;
Microbiological;
Histological;
Routine screening - structural anomalies — trisomy 21;

Question 12

Nuchal Translucency (NT) scan

Answer 12

Between 10-14 weeks gestation;
Thickness of NT measured by ultrasound scan in relation to crown-rump length;
Other anomalies may be detected;

Question 13

Causes of increased NT

Answer 13

Chromosomal - Down syndrome;
Major congenital heart disease;
Skeletal dysplasias;
Diaphragmatic hernia;

Question 14

As maternal age increases, the risk of Down syndrome…

Answer 14

Increases

Question 15

Biochemical serum screening

Answer 15

First trimester -
10-14 weeks gestation (with NT scan);
Accurate dating important to interpret results;
Free beta-human gonadotrophin;
Placenta-associated plasma protein A;
Detection rate of 90% but needs CVS/amnio;

Second trimester -
Alpha-fetoprotein;
Free beta HCG;
Oestriol;

Question 16

Reduced MSAFP levels indicate?

Answer 16

Down syndrome

Question 17

Elevated MSAFP levels indicate?

Answer 17

Neural tube defects;
Anterior abdominal wall defects;
Missed or threatened miscarriage;
Intra-uterine growth retardation;
Multiple pregnancy;
Congenital nephrotic syndrome

Question 18

Indications for targeted prenatal tests: from personal and family history

Answer 18

Family history of congenital structures abnormalities - neural tube defect;

Diagnostic tests: family history of chromosome abnormality;
Family history of a single gene disorder

Question 19

Abnormalities identified in pregnancy

Answer 19

Abnormal screening result;
Abnormal scan (structural, growth, limb shortening);

Question 20

Targeted tests - non invasive

Answer 20

Ultrasound scan - surveillance (eg. growth), 3D scan, Fetal echocardiogram;
Fetal MRI scan;
Molecular testing on fetal cells/ DNA in maternal blood for gender or other conditions;

Question 21

Targeted tests - invasive

Answer 21

CVS;
Amniocentesis;
Cordocentesis;
Fetal tissue biopsy - liver, muscle, skin;

Question 22

Chorionic villus sampling

Answer 22

11-13 weeks;
Transabdominal approach;
Chromosomes;
Direct prep - 1-2 days;
Long term prep - 2 weeks;
Good yield of fetal DNA for molecular tests;
1% miscarriage risk;

Question 23

Amniocentesis

Answer 23

15-16 weeks gestation;
Amniocytes derived from fetal tissues and amnion;
Both amniocytes and supernatant can be used for prenatal tests;
Chromosome analysis takes 2-3 week;
Low yield of fetal DNA;
1% miscarriage risk;

Question 24

Response to prenatal diagnosis

Answer 24

Current pregnancy:
Continue;
Terminate;

Future pregnancy:
No alteration in reproductive plans;
Prenatal screening/testing;
Restriction of family size/adoption;

Question 25

Preimplantation genetic diagnosis (PGD)

Answer 25

Process of testing embryos produced by IVF for inherited disorder; Suitable for couples at substantial risk of transmitting a serious genetic condition to their children - chromosome translocation, x linked disorders, single gene disorders;