Paeds Cases · genetics-dysmorphology-and-metabolism
Normal microarray and developmental delay — genomic testing strategy OSCE
OSCE on counselling a family through a normal chromosomal microarray, justifying escalation to whole-exome or whole-genome sequencing, consent for the variant of uncertain significance and secondary findings, and the plan for re-analysis.
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MRCPCH ClinicalRACP DCE
Prompt
The parents of a four-year-old boy with global developmental delay attend clinic after a normal chromosomal microarray. They are anxious that 'there is nothing wrong genetically' and confused about why more testing is being suggested. Counsel them on what the normal result means, the next test, and the consent points.
Objectives
- Explain what a normal chromosomal microarray does and does not exclude. [1]
- Justify escalation to whole-exome or whole-genome sequencing with an honest yield. [2]
- Conduct pre-test counselling on the variant of uncertain significance and the secondary-findings opt-out. [6] [10]
- Build a plan for re-analysis and a definite review. [2]
References4ShowHide
- [1]Miller DT, Adam MP, Aradhya S, Biesecker LG, Brothman AR, Carter NP Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. American Journal of Human Genetics, 2010.PMID 20466091
- [2]Manickam K, McClain MR, Demmer LA, Biswas S, Kearney HM, Malinowski J Exome and genome sequencing for pediatric patients with congenital anomalies or intellectual disability: an evidence-based clinical guideline of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine, 2021.PMID 34211152
- [6]Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genetics in Medicine, 2015.PMID 25741868
- [10]Miller DT, Lee K, Abul-Husn NS, et al. ACMG SF v3.2 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG). Genetics in Medicine, 2023.PMID 37347242