Module - Paediatric Genomics (SLS421)

STP

Aim of this module

This module will provide the trainee with knowledge and understanding of the role and application of genetic and genomic testing in the diagnosis  and management of paediatric patients with rare inherited diseases, including the implications for other family members.

 The content for this module will focus on (as exemplars): newborns who present as dysmorphic, failure to thrive, ambiguous genitalia or who are hypotonic. those patients who have a clinical suspicion of Duchenne muscular dystrophy, spinal muscular atrophy, Prader-Willi and Angelman syndrome, fragile X syndrome, myotonic dystrophy, cystic fibrosis, disorders of sexual differentiation, children with developmental delay or delayed puberty.

Work-based learning outcomes


  1. Apply an appropriate testing strategy relevant to patients referred for paediatric disorders.
  2. Perform appropriate whole genome analysis for patients referred for paediatric genomic testing.
  3. Perform targeted testing for patients referred with paediatric genetic conditions.
  4. Investigate the clinical significance of variants using a range of bioinformatics tools, following current best practice guidelines.
  5. Interpret and report a range of genetic and genomic testing relevant to paediatric conditions, including the results of diagnostic testing which should encompass appropriate recommendations for patient management.

Work-based Competencies


Learning outcome Title Knowledge
1 1

Select the correct genetic test(s) for samples from patients referred with learning disability.

  • The principal referral reasons that would indicate testing for each of the conditions under investigation.
  • The clinical and scientific basis for the repertoire of genetic testing available to investigate the common range of clinical referrals.
  • Ethical issues associated with patient consent.
  • The clinical utility of genetic testing in patients with learning disabilities.
  • The overlapping and complex testing pipelines where patients referred with learning disability will often sit.
  • This analysis in the context of any previous genetic testing for the patient.
  • The use of this test for other referral reasons (e.g. FRAX).
  • How to recognise the implications of genetic mosaicism in this group of patients.
2 2,4,5

Perform and interpret whole genome analysis from patients with learning disabilities.

  • The technical pathway including its limitations and sensitivities, the essential requirement for good laboratory practice and the risks.
  • How to identify and describe the potential for error, how this is mitigated and its potential effects.
  • Best practice guidelines compared with laboratory practice and any differences between the two.
  • Clinical and scientific aspects of chromosome disorders.
  • The use of digital, light and fluorescent microscopy.
  • The use of ISCN.
  • Internal and external quality assurance (QA) for chromosome analysis.
  • Local laboratory procedures for recording results of chromosome analysis.
  • How to critically appraise relevant literature and databases.
  • The need for further genetic testing, e.g. fluorescence in situ hybridisation (FISH), chromosomal mircroarrays.
3 1,3,4,5

Select an appropriate reflex test and the interpretation within the context of the primary analysis.

  • The added value of targeted analysis (e.g. FISH, MLPA etc.)
  • The technical pathway including its limitations and sensitivities, the essential requirement for good laboratory practice and the risks.
  • How to identify and describe the potential for error, how this is mitigated and its potential effects.
  • Best practice guidelines compared with laboratory practice and any differences between the two.
4 2,3,4,5

Perform the analysis and interpretation of genomic dosage and targeted analysis for the detection of genome anomalies associated with learning disability.

  • The technical pathway including its limitations and sensitivities, the essential requirement for good laboratory practice and the risks.
  • Validation and verification of findings.
  • How to identify and describe potential for error, how is this mitigated and its potential effects.
  • Best practice guidelines compared with laboratory practice and any differences between the two.
  • Microarray data analysis and the use of relevant software.
  • Interpretation and classification of Copy Number Variation (CNVs) according to best practice guidance.
  • The added value of referring for further testing.
  • The counselling issues (e.g. incidental findings).
5 3,5

Interpret results from methylation studies for PWS/AS syndrome.

  • The technical procedure including its limitations and sensitivities, the essential requirement for good laboratory practice and the risks.
  • Identify and describe potential for error, how is this mitigated and its potential effects.
  • Best practice guidelines compared with laboratory practice and any differences between the two.
  • Internal quality parameters and use of interpretive software where applicable.
  • MLPA methodology for the assessment of methylation status.
6 4,5

Prepare full and accurate interpretative clinical reports for patients referred with learning disabilities.

  • How to recognise all tests have been completed to a satisfactory standard for the referral reason.
  • All information has been validated as correct.
  • Selection of correct report template for referral reason.
  • Recommendations for further referral (e.g. clinical genetics). Identify the requirements for any follow up testing, the testing methods available and the appropriate choice of test. Describe any limitations.
  • Use of correct scientific and clinical terminology.
  • Use of relevant databases and the literature in the interpretation of results.
  • Communication of complex scientific information to clinicians and patients.
  • Best practice guidelines compared with laboratory practice and any differences between the two.
  • How to identify pertinent EQA schemes; their role and practice, how these are incorporated into laboratory practice and ISO standards for lab participation in EQA schemes.
7 1,3,4,5

Select the correct genetic tests for patients referred with a suspected neuromuscular disorder.

  • The range of tests suitable for patients presenting with particular neuromuscular symptoms.
  • The genetic alterations and genes responsible for a range of neuromuscular disorders, e.g. B/DMD, DM and SMA.
  • The range of genetic testing relevant to diagnostic and carrier/predictive testing for neuromuscular disorders.
  • The distinction between in-frame and out of frame dystrophin mutations and the ability to interpret B/DMD testing results appropriately.
  • The use of linkage analysis (B/DMD and SMA) and the ability to evaluate the risks of recombination.
8 3,4,5

Perform dosage analysis on a patient sample referred for DMD or SMA and analyse the result of molecular testing using appropriate software.

  • Principles of the techniques, including limitations and sensitivity. 
  • Internal and external quality control.
  • The quality parameters for the test.
  • Use of suitable analysis software.
  • How to recognise samples that require repeat testing or that have failed testing.
  • Accurate recording of results of analysis following local laboratory protocols.
9 5

Perform simple Bayesian analysis to calculate carrier probability in BMD/DMD and SMA.

  • The importance of accurate pedigree construction.
  • Calculation of an a priori and a posterior risk to an individual in a pedigree of being affected with a disorder.
10 4,5

Prepare a range of full and accurate reports relevant to the referrals for testing of neuromuscular disorders.

  • How to recognise all tests have been completed to a satisfactory standard for the referral reason.
  • All information has been validated as correct.
  • Selection of correct report template for referral reason.
  • Recommendations for further referral (e.g. clinical genetics). Identify the requirements for any follow up testing, the testing methods available and the appropriate choice of test. Describe any limitations.
  • Use of correct scientific terminology.
  • Communication of complex scientific information to clinicians and patients.
  • Best practice guidelines compared with laboratory practice and any differences between the two.
  • How to identify pertinent EQA schemes; their role and practice, how these are incorporated into laboratory practice and ISO standards for lab participation in EQA schemes.
  • The calculation of residual probability following molecular testing where appropriate.
  • Use of relevant databases and literature in the interpretation of results.
11 3

Perform a PCR-based test to detect common CFTR mutations.

  • Principles of the technique, including limitations and sensitivity.
  • Internal and external quality control.
  • The quality parameters for the test.
  • Use of suitable analysis software.
  • How to recognise samples that require repeat testing or that have failed testing.
  • Accurate recording of results of analysis following local laboratory protocols.
12 4,5

Prepare a range of full and accurate interpretative clinical reports for paediatric patients referred for Cystic Fibrosis testing.

  • How to recognise all tests have been completed to a satisfactory standard for the referral reason.
  • All information has been validated as correct.
  • Selection of correct report template for referral reason.
  • Recommendations for further referral (e.g. clinical genetics). Identify the requirements for any follow up testing, the testing methods available and the appropriate choice of test. Describe any limitations.
  • Use of correct scientific and clinical terminology.
  • Use of relevant databases and literature in the interpretation of results.
  • Communication of complex scientific information to clinicians and patients.
  • Best practice guidelines compared with laboratory practice and any differences between the two.
  • How to identify pertinent EQA schemes; their role and practice, how these are incorporated into laboratory practice and ISO standards for lab participation in EQA schemes.
  • Implication of a positive result for other family members.

Work-based assessment


Complete 3 Case-Based Discussion(s)
Complete 3 of the following DOPS and/or OCEs
Type Title
DOPS Bisulphite modification and PCR to detect methylation
DOPS FISH analysis using microscopy
DOPS Processing samples for FISH
DOPS Karyotype by image analysis
DOPS Microarray analysis for a patient referred with learning disability
DOPS Analyse results of MLPA analysis
DOPS Interpret and report MLPA data
DOPS Sample preparation for array analysis
DOPS Use bioinformatics tools to interpret clinical significance of array result
DOPS Analyse the results of CF testing
DOPS Perform laboratory set up of CF test
DOPS PCR amplification of a triplet repeat
DOPS Analyse results of FMR1 gene analysis
DOPS Perform basic risk calculation
DOPS Prepare a clinical report for a paediatric patient referred with learning disability
DOPS Prepare a clinical report for a paediatric patient referred for cystic fibrosis
DOPS Prepare a clinical report for a paediatric patient referred with a neuromuscular disorder
OCE 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