Normal microarray and developmental delay — genomic testing strategy OSCE

Objectives

1. Explain what a normal chromosomal microarray does and does not exclude. [1]
2. Justify escalation to whole-exome or whole-genome sequencing with an honest yield. [2]
3. Conduct pre-test counselling on the variant of uncertain significance and the secondary-findings opt-out. [6] [10]
4. Build a plan for re-analysis and a definite review. [2]

Candidate brief

Twelve-minute station. The parents and their four-year-old son are present. The referral is global developmental delay. The microarray is normal. The parents have interpreted the normal result as reassurance that no genetic cause exists, and they are wary of more testing. [1]

Expected actions

• Acknowledge the parents' relief and gently correct the misinterpretation: a normal microarray excludes only the common copy-number causes. [1]
• Explain that microarray does not detect single-base spelling changes in genes or repeat expansions, so a genetic cause remains possible. [1]
• Introduce whole-exome or whole-genome sequencing as the next test, quoting an honest yield and the benefit of a trio approach. [2]
• Counsel on the variant of uncertain significance — a real finding whose meaning is not yet known — and on the secondary-findings opt-out. [6] [10]
• Set a definite review and explain that a negative result can be re-analysed as knowledge grows. [2]

Parent actor prompts

• "The doctor said the chromosome test was normal, so there is nothing wrong with him genetically. Why are you sending more tests?" [1]
• "What if this new test finds something else — something in me? I do not want to know that." [10]

Model communication lines

"The normal microarray is good news because it rules out the common large chromosome changes that cause developmental delay. But it is like checking the chapter headings of a book — it does not read the individual words. A spelling mistake in a single gene, or a different kind of change called a repeat expansion, would not show up on that test, and those are common causes of developmental delay too. So the normal result does not mean there is no genetic cause; it means we have not found it yet. The next test, exome or genome sequencing, reads the genes letter by letter, and it finds an answer in about a third of children in this situation. I would test you both as well, because comparing you helps us interpret the result. There are two things I want you to know before we go ahead. First, we may find a change whose meaning we are not yet sure of — we would not treat that as a diagnosis, and we would discuss it carefully. Second, the test can pick up unrelated findings, for example a gene linked to cancer risk in adults — you can choose whether to receive those, and there is no wrong answer. Whatever the result, I will book a time to go through it with you, and if it is negative we can re-analyse it in the future as our knowledge grows." [1] [2] [6] [10]

Marking

Pass: correctly explains what a normal microarray excludes and does not exclude; justifies escalation to exome or genome sequencing with an honest yield and the trio concept; counsels on the variant of uncertain significance and the secondary-findings opt-out without overwhelming the family; sets a definite review and offers re-analysis. [1] [2] [10] Fail: reassurance that a normal microarray excludes a genetic cause; offering sequencing without counselling on the variant of uncertain significance or secondary findings; or an open-ended wait with no review plan. [6]