Rare Disease 2 —
Training activity: 2

Details

Review referrals; analyse, interpret and report the results of testing for Spinal Muscular Atrophy (SMA) to include:

• Diagnostic testing
• Carrier/familial testing

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 are the intended outcomes of the training activity?

• How will this activity demonstrate your ability to triage referrals and perform targeted analysis for both diagnostic and carrier/familial cases?
• Do you understand the specific dosage analysis techniques used in your lab to assess SMN1 and SMN2 copy numbers?
• Are you familiar with the relevant national guidelines for SMA testing, including the criteria for defining carrier status?
• What specific metrics (e.g., probe ratios, standard deviations) will you monitor to ensure the data is robust for a clinical report?
• How does your interpretation—specifically the SMN2 copy number—directly inform modern clinical management and eligibility for modulator treatments?

What do you anticipate you will learn from the experience?

• What insights do you hope to gain regarding the genomic architecture of the SMN locus and the nuances of interpreting borderline or atypical dosage results?
• What do you already know about the genetic mechanisms underlying SMA (e.g., homozygous deletions vs. point mutations)?
• How do you anticipate this activity will improve your ability to communicate complex results to healthcare professional colleagues?

What actions will you take in preparation for the experience?

• What literature on SMA genetics, testing methodologies, and national recommendations for reporting will you consult?
• Have you planned to discuss previous cases, particularly those involving carrier testing or complex familial patterns?
• What potential difficulties do you anticipate, such as identifying carriers with two copies on one allele or managing urgent referrals for symptomatic infants?
• How do you feel about the professional responsibility of reporting results that have significant prognostic implications for the patient and recurrence risks for the family?
• Under what circumstances (e.g., an unusual dosage pattern or a rare variant in SMN1) will you seek immediate clarification or advice from a senior scientist to ensure you are working within your level of ability?

In action

What are you doing?

• How are you currently approaching the analysis of SMA targeted genomic dosage data?
• Why are the specific genes you are focusing on, such as SMN1 and SMN2, critical for this analysis?
• How are you determining copy numbers and identifying deletions or duplications in real-time?
• Which parts of the analysis feel intuitive, and which require conscious effort (e.g. applying best practice for complex carrier patterns)?

How are you progressing with the activity?

• How effective are your methods in identifying and characterising relevant dosage changes?
• How are you managing challenges like borderline copy number changes, potential ‘2+0’ carrier status, or distinguishing deletion/duplication types within the SMN locus?
• What insights are you gaining regarding the genomic architecture of the SMN locus as the data unfolds?
• How do your current findings connect to your existing knowledge of SMA inheritance and typical dosage alterations?

How are you adapting to the situation?

• Which alternative strategies, such as reviewing QC metrics or adjusting analysis parameters, are you considering for ambiguous results?
• How are you identifying the need for immediate clarification or advice on results that deviate from expectations?
• How are you ensuring your interpretation remains within your professional scope of practice and aligns with the clinical referral?
• In what ways is your interpretation accounting for the implications of dosage alterations on diagnosis, prognosis, and treatment options?

On action

What did you notice?

• How would you summarise the key aspects of the targeted genomic dosage analysis tasks you completed for SMA?
• Which specific referral reasons (diagnostic vs. carrier/familial) and clinical details most significantly influenced your final interpretation?
• What were your technical findings regarding the copy numbers of SMN1 and SMN2, and what range of results (e.g. homozygous deletions, single copies, multiple copies) did you encounter?
• Which unusual or unexpected dosage patterns did you identify that required you to adjust your initial analysis plan?

What did you learn from the activity?

• How has this activity enhanced your understanding of the genomic architecture of the SMN locus and the common alterations associated with SMA?
• What insights did you gain regarding the clinical significance of SMN2 copy numbers in relation to disease severity and modern treatment options?
• How successful were you in accurately determining carrier status, and what did you learn from resolving challenges such as complex dosage patterns or borderline results?
• In what ways did your ‘reflection-in-action’ influence the final accuracy and technical quality of your interpretation?
• How does mastering this targeted analysis contribute to your ability to provide a safe and high-quality service in your future post-programme practice?

What will you take from the experience moving forward?

• Do you require further practice in identifying specific types of deletions or interpreting results in the context of incomplete penetrance?
• What new strategies will you adopt for reviewing QC metrics or for troubleshooting borderline results in future SMA cases?
• Which specific ‘next steps’—including reviewing national guidelines or discussing cases with senior colleagues—will you take to consolidate your learning?
• What support or resources, such as specific dosage analysis platforms or databases, have you identified as necessary to further develop your expertise in this area?

Beyond action

Have you revisited the experiences?

• Revisit your previous interpretations of SMA dosage data. Have any national recommendations for SMA testing or reporting changed since you first completed this activity?
• Compare your SMA experience with other training activities that involve quantitative genomic data, such as copy number variant (CNV) analysis. What similarities or differences do you notice in the analytical and interpretative processes?
• Review your reflections on this training activity alongside other paediatric genetic disorders. What broad learning points have emerged regarding targeted genomic testing in paediatrics?
• Discuss challenging cases or unexpected findings with colleagues. Has their perspective offered new insights or alternative interpretations that you hadn’t previously considered?

How have these experiences impacted upon your current practice?

• Recognise how your initial experiences with SMA have contributed to your broader understanding of gene dosage effects. How has this foundation influenced your approach to interpreting results for other genetic conditions?
• Evaluate how you have applied these dosage analysis skills in subsequent training activities. Have you become more confident in identifying technical pitfalls or limitations of the assay?
• Consider how this learning supports your preparation for observed ‘in-person’ assessments, such as Case-based Discussions (CBD) or Direct Observations of Practical Skills (DOPS) related to paediatric genomics.

How might these experiences contribute towards your future practice?

• Can you now more effectively explain the technical principles behind dosage analysis and the clinical significance of various results (e.g., the impact of SMN2 copy number on prognosis) to others?
• Identify the high-level skills you are developing, such as clinical reasoning and technical troubleshooting, which will be vital for your future career.
• Identify clear next steps to stay current, such as keeping abreast of new technologies for dosage analysis or expanding your knowledge of other rare dosage-related 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.