Rare Disease 2 —
Training activity: 4

Details

Review referrals; analyse, interpret and report the results of testing for Prader-Willi syndrome.

Type

Developmental training activity (DTA)

Evidence requirements

Evidence the activity has been undertaken by the trainee​.

Reflection on the activity at one or more time points after the event including learning from the activity and/or areas of the trainees practice for development.

An action plan to implement learning and/or to address skills or knowledge gaps identified.

Reflective practice guidance

The guidance below is provided to support reflection at different time points, providing you with questions to aid you to reflect for this training activity. They are provided for guidance and should not be considered as a mandatory checklist. Trainees should not be expected to provide answers to each of the guidance questions listed.

Before action

What does success look like?

• How will you demonstrate your ability to triage referrals and perform targeted or chromosomal analysis for imprinting defects?
• What fundamental knowledge of methylation studies (e.g., MS-PCR, MS-MLPA) and copy number assays (e.g., array CGH) is required for PWS diagnosis?
• How will you ensure you have reviewed established diagnostic algorithms and national reporting guidelines for imprinting disorders?
• Which technical metrics (e.g., methylation ratios, signal strength) are essential to monitor for a safe, high-quality service?

What is your prior experience of this activity?

• How do you feel about embarking on this technically complex analysis with significant diagnostic implications for patients and families?
• What challenges do you anticipate, such as interpreting subtle methylation changes, identifying mosaicism, or integrating molecular and cytogenetic data?
• In which situations—such as findings contradicting the clinical phenotype—will you seek immediate advice from a senior specialist?
• How will you draw upon your existing knowledge of genomic imprinting and the parental origin of genetic material?

What do you anticipate you will learn from the experience?

• What insights do you hope to gain regarding the various genetic mechanisms (e.g., deletions, UPD, imprinting centre defects) leading to PWS?
• In what ways will this activity improve your ability to interpret genomic variants and communicate clinical implications to healthcare colleagues?

What additional considerations do you need to make?

• How will you prepare by reviewing epigenetic literature and previous PWS cases from departmental archives?
• How will you clarify the nuances of borderline or atypical methylation results?

In action

What are you doing?

• How are you currently approaching the specific analytical steps for Prader-Willi Syndrome (PWS) results?
• Why is the data you are reviewing—such as methylation studies or copy number assays—specifically relevant to investigating imprinting disorders?
• What decisions are you making in the moment as you evaluate data for evidence of abnormal imprinting, uniparental disomy (UPD), or microdeletions in the 15q11-q13 region?
• Which aspects of your practice feel intuitive, and which—such as ensuring the interpretation carefully considers parental origin—require more conscious effort?

How are you progressing with the activity?

• How effective are your current strategies in distinguishing between the different genetic mechanisms (deletions, UPD, or imprinting centre defects) that lead to PWS?
• How are you managing real-time challenges such as interpreting subtle methylation changes, identifying mosaicism, or handling results that deviate from expected patterns?
• In what ways do your findings align with your understanding of the imprinted genes within the 15q11-q13 region and their distinct clinical phenotypes?

How are you adapting to the situation?

• Which alternative or supplementary analyses, such as testing parental samples, are you considering for cases where it is difficult to differentiate between potential diagnoses?
• How are you identifying the point where you need to seek immediate support or guidance from a senior colleague or imprinting specialist regarding an atypical case?
• How are you ensuring that your real-time interpretation remains strictly within your professional scope of practice and aligns with established laboratory protocols?

On action

What happened?

• How would you summarise the key data and specific types of assays (e.g., MS-PCR, MLPA, or array CGH) involved in this PWS investigation?
• Which essential clinical details from the referral and specific laboratory results (e.g., indicative of PWS vs. Angelman Syndrome) were most significant to your findings?
• Did you identify any results suggestive of alternative imprinting defects or unusual findings that deviated from standard expectations?
• How did you feel while managing the technical and clinical complexity of this imprinting disorder investigation?

How has this experience contributed to your developing practice?

• How has your understanding of the different molecular mechanisms leading to PWS (e.g., 15q11-q13 deletions, UPD, or imprinting centre defects) developed through this activity?
• In what ways did you successfully resolve challenges, such as molecular results inconsistent with clinical presentation or difficulties in distinguishing between epigenetic defects?
• How did your ‘reflection-in-action’ (real-time decisions during analysis) influence the technical accuracy and outcome of the investigation?
• In what ways does mastering the interpretation of complex imprinting disorders relate to your requirements for post-programme practice as a Clinical Scientist?

What will you take from the experience moving forward?

• What specific areas, such as the nuances of the 15q11-q13 critical region or the clinical differentiation between PWS and AS, require further study?
• Which ‘next steps’—including reviewing diagnostic algorithms, attending specialist seminars, or discussing cases with experts—will you take to consolidate this learning?
• How will you adjust your future practice to be more attentive to specific result patterns or better utilise new resources for interpretation?
• What additional support, such as specialist imprinting databases or expert mentorship, have you identified as valuable for your ongoing professional development?

Beyond action

Have you revisited the experiences?

• Evaluate and re-evaluate your previous experiences of analysing and interpreting results for imprinting disorders like PWS/AS to determine how your understanding of these complex molecular mechanisms has evolved.
• Compare this experience with other training activities where you analysed epigenetic data or parent-of-origin effects to develop a more comprehensive understanding of non-Mendelian inheritance patterns.
• Revisit your reflections from a number of related activities as part of a module review to identify patterns in your learning or areas where your understanding has significantly deepened over time.
• Discuss specific cases with clinical colleagues to see if their perspective on the challenges of diagnosis and management has changed your own view of the situation.

How have these experiences impacted upon your current practice?

• Consider how your initial exposure to PWS/AS analysis has shaped your current approach to interpreting results for other disorders with potential epigenetic mechanisms.
• Are you now more likely to consider imprinting as a possible explanation for unusual inheritance patterns encountered in your routine practice?
• How have you applied the knowledge of imprinting in subsequent analyses or discussions, such as contributing more effectively to multidisciplinary team (MDT) meetings?
• How has your confidence in articulating complex genetic findings and their implications grown since this initial training activity?

How might these contribute towards your future practice?

• Can you now confidently explain the different genetic and epigenetic mechanisms leading to PWS and AS and the rationale for different testing approaches to healthcare professional colleagues?
• Identify future learning goals, such as staying informed about advancements in testing technologies for imprinting disorders or developing expertise in interpreting complex methylation patterns.
• Identify the transferable skills you have developed, such as clinical reasoning and diagnostic integration, which will be vital for your future career as a Clinical Scientist.
• Consider how this learning will support your preparation for observed ‘in-person’ assessments, such as Case-based Discussions (CBD) or Observed Communication Events (OCE) involving imprinting disorders.

Relevant learning outcomes

#	Outcome
# 1	Outcome Review referrals for patients referred for rare disease genomic testing.
# 2	Outcome Analyse, interpret and report results for diagnostic, presymptomatic and familial/carrier rare disease genomic testing.
# 3	Outcome Perform targeted analysis, whole genome analysis, and chromosomal analysis for patients referred for rare disease genomic testing.
# 4	Outcome Interpret genomic variants to investigate their clinical significance for patients referred for rare disease genomic testing.
# 7	Outcome Employ specialist knowledge of rare disease genomic testing to deliver a safe and high-quality service.
# 8	Outcome Demonstrate appropriate communication skills with healthcare professional colleagues to inform the clinical management of patients referred for rare disease genomic testing.