Integration of chromosomal microarray into paediatric clinical care in Hong Kong

Abstract

Chromosomal microarray (CMA) has emerged as a major tool to identify unbalanced chromosomal aberrations in children and is recommended as the first tiered investigation for intellectual disability, autism spectrum disorders and multiple congenital anomalies. While the clinical interpretation and genetic counseling remain as ongoing challenge, data about potential downstream benefits and harms of CMA is lacking, especially in paediatric population. Our objective is to evaluate the clinical impact of CMA on medical management in children. In 2011-2012, we performed high resolution CMA using the NimbleGen 135k oligonucleotide array on 240 children in a university-affiliated paediatric unit in Hong Kong. By retrospective chart review, descriptive and multivariate analyses are performed to understand the association between CMA results and change in the medical management. The detection rate of pathogenic/probably pathogenic chromosomal aberrations is 20% in our cohort. While detailed analysis is underway, it is clear that CMA detects chromosomal changes missed by karyotype in some patients, while in others it provides significant information in addition. Importantly these findings can be medically actionable and/or have major implications for family members. The insights we have learned from some of our patients have wider implications for the medical community e.g. the recommendation of cardiac assessment for patients with 17p13.3 duplication (Eur J Med Genet 2012; 55(12):758-62) and renal surveillance for patients with Xq22.3 deletion (Esophagus, in press), and have resulted in publications in peer-reviewed journals. One family with a neurodevelopmental phenotype and a probably pathogenic CMA finding has decided not to receive any further information as the parents realised that 'knowing more may not be better'. The potential of CMA findings to impact, positively and negatively, on patients is tremendous and warrants careful evaluation. Our findings will be instructive in anticipating the impact of whole genomic analyses on medical management and downstream utilisation of health services.