Genetics 5-Prenatal Diagnosis of Genetic Diseases

Question 1

What is the nuchal scan

Answer 1

Done at 12 weeks
Uses of the Nuchal Scan: 
Date the pregnancy 
Multiple Pregnancies  
Major Foetal Abnormalities 
Early Miscarriage 
Assess risks of Down Syndrome and other chromosomal abnormalities

Question 2

Nuchal Translucency (NT)

Answer 2

10-14 weeks
Measure of the fluid at the back of the baby’s neck.
NT is usually below 3.5mm

Increased >3mm can indicate:
Chromosome Abnormalities - e.g. Down’s, Patau, Turner, Edwards NT + maternal age detects up to 75% of Down Syndrome - 5% false positive rate (combined test)
Birth Defects:
Cardiac Anomalies
Pulmonary Defects (e.g. diaphragmatic hernia)
Renal Defects
Abdominal Wall Defects (e.g. omphalocele)
Skeletal Dysplasia

Question 3

When is prenatal testing arranged?

Answer 3

Following abnormal findings at nuchal or mid-trimester scan.

Following results of combined test which give an increased risk of Down Syndrome.

If previous pregnancy affected with a condition e.g. Down Syndrome, Cystic Fibrosis

If the parent(s) is a carrier of chromosome rearrangement or genetic condition e.g. Duchenne Muscular Dystrophy, Huntingdon’s Disease

Family History of genetic condition

Question 4

Aims of Prenatal Testing

Answer 4

To inform and prepare parents for the birth of an effected child.

In utero treatment could be offered.

Aids management of the rest of the pregnancy

Allows parents to prepare for complications at or after birth.

To allow TERMINATION of an affected foetus.

Question 5

What types of prenatal tests

Answer 5

non invasive:
Ultrasound/mri

Minimally invasive:
Maternal blood test
Cell-free foetal dna

Invasive:
Chorionic Villus Sampling (CVS)
Amniocentesis

Question 6

What are the uses of non invasive scans?

Answer 6

Ultrasound
Early/dating scan (can be done from 5 weeks but best from 9 weeks)
Nuchal Translucency and nasal bone
High level/anomaly scan

Foetal MRI
20+ weeks
High level and anomaly scan can be diagnostic - showing cleft lip, limb deformity or cardiac problem.
It can also show soft markers for other problems.
Nasal Bone - soft marker - presence or absence can indicate Down Syndrome.
When taken alongside NT and maternal age, looking at the Nasal Bone increases the sensitivity of DS screening.

Foetal Cardiac Scans can show cardiac problems - only done if the other scans indicate potential problem.

Question 7

Uses of minimally invasive prenatal tests

Answer 7

Types of Maternal Serum Screening:
1st Trimester - 11-14 weeks - done alongside the NT measurement (looks for the presence of hCG (human chorionic gonadotrophin) and PAPP A (pregnancy associated plasma protein A)).
2nd Trimester - 16-20 weeks - done if they are booked in later in pregnancy - looks for hCG and PAPP A and AFP (alpha foetal protein) and uE3 (oestriol).

Question 8

What is cell free feotal dna testing

Answer 8

OFFERED PARTICULARLY IF THE BABY HAS A CHANCE OF HAVING AN X-LINKED CONDITION.
So only boys can be affected and girls can be carriers.
This testing is done to determine the sex of the baby.
A small amount of Foetal DNA will be in the maternal blood.
A blood test can be done to isolate that DNA and to look for the presence of the Y chromosome.
If the Y chromosome is present, you know the baby is male.
cffDNA is first detectable from 4-5 weeks but is more accurately detected around 9 weeks.

Uses of cffDNA Testing
Offered primarily when there is a sex-linked condition in the family to sex the pregnancy e.g. DMD
Blood Test - 9 weeks
Test detects SRY gene (sex-determining region Y) on the Y chromosome - determines whether the foetus is male or female.

Question 9

Describe Chorionic Villus Sampling (CVS)

Answer 9

11-14 weeks
1-2% Risk of Miscarriage
Transabdominal or Transvaginal
Chorionic Villus - part of the developing placenta - has the same DNA as the foetus
Gives an earlier result than amniocentesis - important for patients deciding on termination of pregnancy

Question 10

Describe Amniocentesis

Answer 10

16+ weeks
Takes sample of amniotic fluid which contains foetal cells
Up to 1% risk of miscarriage
Performed later than CVS
Performed by sticking a needle through the abdomen

Question 11

What type of test is done with the DNA sample from CVS or Amniocentesis?

Answer 11

Karyotype - done if there is a chromosomal abnormality in the family. E.g. if the parents are carriers of a balanced translocation.
Results in 2 weeks (dependent upon the cells growing)

QF-PCR (Quantitative Fluorescence PCR)
All prenatal samples have a QF-PCR test
Test for T13, T18 and T21 (and sex chromosomes if sex chromosome disorder is suspected)
Results: 24-48 hours

Question 12

If there is a known reproductive risk what are the options

Answer 12

Conceive naturally - no prenatal testing

Conceive naturally - have prenatal testing

Egg and/or Sperm Donors

Adoption

Choose not to have children

Pre-implantaion Genetic Diagnosis (PGD)

Question 13

What is the process for preimplantation genetic diagnosis

Answer 13

Stimulation of the ovaries - stimulate the ovaries to produce more eggs

Eggs are collected

Insemination - either by IVF (sperm and egg placed together in a culture dish) or ICSI (Intra-Cytoplasmic Sperm Injection - injection of a single sperm into each egg).

Fertilisation

Embryo Biopsy - once embryo gets to about 8 cells in size, a cell is removed by embryo biopsy.

Embryo Testing

Embryo Transfer - embryos that don’t have the genetic condition or are carriers are considered for embryo transfer (maximum 2 are transferred)

Pregnancy Test

Question 14

What is the Eligibility Criteria for PGD

Answer 14

Female partner is under 40

Female partner has BMI between 19 and 30

Both partners are non-smokers

No living unaffected children from the relationship

Known risk of having a child affected by a serious genetic condition

A licence is required from the HFEA for each genetic condition or indication

Eligible couples are usually funded for three rounds of PGD