A Practical Guide to Chromosome Microarray Interpretation for Paediatricians

INTRODUCTION: Chromosome microarray (CMA) is a test commonly ordered by general paediatricians. It has diagnostic yield between 10%-15% in individuals with neurodevelopmental delay, autism and/or multiple congenital abnormalities. CMA identifies copy number variants (CNV) including deletions and duplications, which may be pathogenic, variants of uncertain significance or benign. Interpretation of the clinical significance of these results can prove challenging without a structured approach. Readily available practical guidelines are lacking. AIMS: We aim to equip the general paediatrician with a practical guide to determine the clinical relevance of a CMA result, and when a referral to clinical genetics is recommended. RESULTS: We discuss the clinical indications for CMA and anticipated diagnostic yield for different conditions. We provide an overview of pre-test counselling and an approach to discussing results. A table is provided to guide interpretation of results and management implications for differing CMA results including pathogenic CNVs, variants of uncertain significance, variants in neurosusceptibility loci, incidental findings or regions of homozygosity. We discuss the value of segregation studies, potential implications for future family planning, limitations of testing and indications for referral to clinical genetics or other specialists, and further genomic testing. CONCLUSION: Paediatricians are increasingly expected to understand the implications of common genetic tests. A practical approach to ordering and interpreting CMA will help address much of the complexity around these results and also streamline referrals to genetics.