Prenatal genomic testing for USS detected fetal structural anomalies TOG 2023

Question 1

What proportion of FSA have a genetic or chromosomal abnormality?

Answer 1

50%
- Associated increased morbidity/mortaility

Question 2

What % of pregnancies are effected by fetal structural anomalies?

Answer 2

3-5%

Question 3

What proportion of underlying genetic or chromosomal abnormality can be detected with QF-PCR, G-banding karyotype and CMA (chromosomal microarray)

Answer 3

60%

Cumulative diagnostic yield 25%

Question 4

How can fetal DNA be obtained?

Answer 4

Invasive testing Amnio or CVS

Question 5

With invasive testing
- Risk of miscarriage
- Risk of maternal contrimation

Answer 5

• O.5%
  -1-2%

Question 6

Which test is normally 1st carried out>

Answer 6

QF-PCR (replaced FISH) to detect aneuploidy 13, 18, 21, sex chromosomes

Question 7

If QF-PCR detects aneuploidy 13, 18, 21, sex chromosomes, what test next?

Answer 7

G-banding karyotype ?inherited structural chromosomal rearrangement

Question 8

If QF-PCR negative, what next test?

Answer 8

Chromosomal microarray (CMA)

If:
(i) isolated nuchal translucency≥3.5 mm when thecrown-rump length measures from 45 mm to 84 mm (atapproximately 11+0weeks to 13+6weeks); (ii) one or moreFSAs identified on ultrasound scan; or (iii) fetuses with a sexchromosome aneuploidy that is unlikely to explain theultrasound anomaly (

3rd testing - NHS exome sequencing

Question 9

How to obtain DNA if NND?

Answer 9

Umbilical cord blood @ delivery

Fresh frozen skin, liver, spleen

Placental biopsy

Or PM fetal blood → NGS

Question 10

What is QF-PCR
average turnaround time

Answer 10

Markers to specific areas of chromosomes, amplified using DNA polymerase,

Detects aneuploidies

48 hours

Question 11

What is G banding karyotyping

Answer 11

Giemsa staining to visulaise number and macrostructure

GS - Mosaicism, polyploidy and re-arrangments

Will not detect microdelevtions

Question 12

What is chromosome mircoarray?

Average turn around time

Answer 12

Oligonucleotides probes -complimentry DNA sequences

Can detect microdeletions/duplications/loss of heterozygosity, copy number variant

Cannot detect balanced translocations, small deletions

10-14days

Question 13

Prenatally CMA has what % better diagnostic yield than QF-PCR/karyotype?

Answer 13

3.5-6%

Question 14

Most common copy number variant detected by CMA?

Answer 14

22q11.2 micro deletion (DiGeorge syndrome_

Question 15

Exone sequencing codes what proportion of the genetic code?

Answer 15

1% 30 million base pairs

Question 16

Additional Dx found in NGS?

Answer 16

Diagnostic genetic variant 8.5%
Uncertain significance 3.9%