Prenatal Genomics

Module details

Title

Prenatal Genomics

Type

Specialist

Module code

SLS420

Credits

10

Requirement

Compulsory

Aim of this module

This module will provide the trainee with knowledge and understanding of the role and application of genetic and genomic testing for prenatal testing, including screening and diagnosis and . It will also consider the potential impact of prenatal testing on the patient and their family.

 

Competencies

#	Learning outcome	Competency	Action
# 1	Learning outcome 1,5	Competency Choose the correct prenatal sample pathway for the sample received.	Action View
# 2	Learning outcome 1,2,3,5	Competency Perform the analysis and interpretation of rapid aneuploidy screening results.	Action View
# 3	Learning outcome 4,5	Competency Prepare full and accurate interpretive clinical reports for rapid aneuploidy testing.	Action View
# 4	Learning outcome 1,2,3,5	Competency Perform the analysis and interpretation of Prenatal Chromosomal Microarray.	Action View
# 5	Learning outcome 4,5	Competency Prepare full and accurate interpretive clinical reports for Prenatal Chromosomal Microarray testing.	Action View
# 6	Learning outcome 1,2,3,5	Competency Perform the analysis and interpretation of Prenatal Diagnosis for single gene mutations.	Action View
# 7	Learning outcome 4,5	Competency Prepare full and accurate interpretive clinical reports for Prenatal Diagnosis of single gene disorders.	Action View
# 8	Learning outcome 1,2,3,5	Competency Perform follow up genetic tests, to include directed FISH and karyotype analysis (generally regional specific assays).	Action View
# 9	Learning outcome 1,2,3,5	Competency Assist in the analysis and interpretation of Non-Invasive Prenatal Testing (NIPT).	Action View
# 10	Learning outcome 4,5	Competency Prepare full and accurate interpretive clinical reports for Non- Invasive Prenatal Diagnosis (NIPD).	Action View

Assessments

You must complete:

• 2 case-based discussion(s)
• 2 of the following DOPS/ OCEs:

Analyse and record results for single gene mutation analysis	DOPS
Analyse and record results of QF PCR data using fragment analysis software	DOPS
Set up FISH slide for aneuploidy detection	DOPS
Analyse FISH slide and record results	DOPS
Analyse results of a prenatal array using appropriate software package and record results	DOPS
Set up PCR for aneuploidy screen	DOPS
Set up PCR for targeted single gene mutation analysis	DOPS
Perform duty scientist checking of samples referred for aneuploidy screening	DOPS
Analyse results of NIPT	DOPS
Prepare a patient report for NIPT	DOPS
Prepare a patient report for aneuploidy screening	DOPS
Use bioinformatics tools to interpret clinical significance of a prenatal array result	DOPS
Participate in an MDT meeting with other healthcare professionals	OCE
Take a patient history can be undertaken in virtual patient environment	OCE
Discuss patient results with a healthcare professional telephone or in person	OCE

Learning outcomes

1. Apply an appropriate testing strategy (the right sample, the right test, for the right reasons) meeting all relevant KPIs (key performance indicators, however defined).
2. Analyse and interpret results of specific defined tests.
3. Identify and respond appropriately to results.
4. Compose fully interpreted clinical reports guided by current best practice guidance.
5. Act in accordance with the high level of laboratory risk associated with prenatal testing and within limits of their responsibilities.

Learning outcomes

1. Describe the principles of screening programmes and the difference between screening and diagnosis in the context of prenatal testing.
2. Explain the maternity clinical care pathway with respect to a strategy for prenatal testing and prenatal diagnosis of genetic and genomic disease.
3. Explain Rapid Aneuploidy screening and testing, including combined screening (biochemical and ultrasound scan) and the range of laboratory methods.
4. Explain prenatal diagnosis for genetic and genomic disease, including NIPT/D and invasive testing.
5. Discuss and debate the clinical, scientific, ethical and legal dimensions of prenatal diagnosis.
6. Recognise and describe the specific clinical risks associated with prenatal screening and testing, as well as the potential impact for the patient and their family.

Indicative content

Screening Programmes

• The clinical, scientific, ethical and social requirements for prenatal testing
• The organisation,   delivery    and   performance   of    the    national screening programme for aneuploidy and fetal anomaly
• The follow up pathways for screening programme positive cases

 Maternity Clinical Care Pathways for prenatal testing

• The context of prenatal testing within the maternity clinical care pathway
• Specific diagnostic methods appropriate for screen positive results including:
  • Rationale
  • Limitations
  • Best Practice Guidelines (BPG)
  • National guidance and/or strategy, for example, the National Fetal Anomaly Screening Programme
• Key performance indicators (KPIs) as currently offered in the UK
• An awareness of developing methods, including those offered elsewhere but not formally adopted in the UK

 Prenatal testing

All aspects of:

• Rapid Aneuploidy testing using current technology
• Prenatal Microarray
  • Validate and verify results
• Targeted mutation testing including:
  • suitability of platforms
  • sensitivity and specificity
  • follow up testing (which may include FISH or karyotyping or specific molecular testing for example)
  • the reason for the test, reasons for referral and the likely outcomes
  • the patient cohort
  • prior information required
  • the tissue for testing (blood, Chorionic Villus Sampling (CVS), amniotic fluid)
  • the potential for unexpected outcomes and how this is mitigated or dealt with
• Limitations of each of the above tests, including sensitivity and specificity including:
  • Mosaicism, and confined placental mosaicism
  • Maternal cell contamination
  • Polysomy
  • Allele drop-out
  • Twin pregnancies
• BPG and KPI for each of the tests listed above
• Result confirmation, when this is appropriate, by which method and at which time point (pre or post-natal)
• External Quality Assurance (EQA) schemes for each of the above tests
• Analysis of results, including identification of poor or substandard test performance and corrective action
• Interpret archived results based on older technologies and the implication and limitation of these results for the patient and family
• Awareness of the importance of turnaround time in the pathway of care

 Interpretation and reporting of results to include:

• Utilisation of appropriate validated algorithms which are likely to include critical appraisal of literature, laboratory and publicly accessible databases
• Classification of finding where appropriate (pathogenic, likely pathogenic )
• Clinical report writing
• Role of multi-disciplinary team (MDT) meetings to aid interpretation

 Non-invasive prenatal testing/diagnosis (NIPT/D)

• accessibility for pregnant women (NHS commissioned tests, private providers, research projects)
• technical principles
• diagnostic scope
• sensitivity and specificity
• incidental findings for the following purposes:
• fetal sexing
• familial single gene mutations
• Trisomy 21 and other aneuploidies
• other chromosome imbalance

 Ethical and legal considerations of prenatal diagnosis

• Consent for prenatal testing, storage of patient material and informed choice
• High risk nature of samples in relation to patient decision making
• Follow-up management including termination of pregnancy
• Legislation associated with pregnancy and the unborn fetus

Activities

• Observe obstetric ultrasound scans; critically reflect on your observation and discuss the possible outcomes and implications for patient care with your
• Observe CVS and /or Amniotic Fluid sampling; critically reflect on your observation and discuss the possible outcomes and implications for patient care with your
• Attend a fetal medicine genetics clinic or multidisciplinary team meeting (MDT) and identify the role and importance of the clinic or MDT for patient pathways and
• Shadow genetic screening co-ordinators and discuss with them their role, responsibilities and interaction with the genetics laboratory and national screening

 Gain experience of at least three of the following and reflect on their importance, application and impact on patient management:

• NIPT for aneuploidy detection
• Biochemical screening for aneuploidy
• PCR using excess material for rapid aneuploidy screening
• Chromosomal microarray on any DNA sample (pre or post-natal)
• FISH on any pre or post-natal sample
• Karyotyping on any pre or post-natal sample