title: The clinical impact of chromosomal microarray on paediatric care in Hong Kong.
abstract: OBJECTIVE
  To evaluate the clinical impact of chromosomal microarray (CMA) on the management of paediatric patients in Hong Kong.
  
  
  METHODS
  We performed NimbleGen 135k oligonucleotide array on 327 children with intellectual disability (ID)/developmental delay (DD), autism spectrum disorders (ASD), and/or multiple congenital anomalies (MCAs) in a university-affiliated paediatric unit from January 2011 to May 2013. The medical records of patients were reviewed in September 2013, focusing on the pathogenic/likely pathogenic CMA findings and their "clinical actionability" based on established criteria.
  
  
  RESULTS
  Thirty-seven patients were reported to have pathogenic/likely pathogenic results, while 40 had findings of unknown significance. This gives a detection rate of 11% for clinically significant (pathogenic/likely pathogenic) findings. The significant findings have prompted clinical actions in 28 out of 37 patients (75.7%), while the findings with unknown significance have led to further management recommendation in only 1 patient (p < 0.001). Nineteen out of the 28 management recommendations are "evidence-based" on either practice guidelines endorsed by a professional society (n = 9, Level 1) or peer-reviewed publications making medical management recommendation (n = 10, Level 2). CMA results impact medical management by precipitating referral to a specialist (n = 24); diagnostic testing (n = 25), surveillance of complications (n = 19), interventional procedure (n = 7), medication (n = 15) or lifestyle modification (n = 12).
  
  
  CONCLUSIONS
  The application of CMA in children with ID/DD, ASD, and/or MCAs in Hong Kong results in a diagnostic yield of ∼ 11% for pathogenic/likely pathogenic results. Importantly the yield for clinically actionable results is 8.6%. We advocate using diagnostic yield of clinically actionable results to evaluate CMA as it provides information of both clinical validity and clinical utility. Furthermore, it incorporates evidence-based medicine into the practice of genomic medicine. The same framework can be applied to other genomic testing strategies enabled by next-generation sequencing.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Victoria Q
authors.initials: VQ
authors.lastname: Tao
authors.affiliation: Department of Obstetrics and Gynecology, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
authors.forename: Kelvin Y K
authors.initials: KY
authors.lastname: Chan
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Yoyo W Y
authors.initials: YW
authors.lastname: Chu
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Gary T K
authors.initials: GT
authors.lastname: Mok
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Victorian Clinical Genetics Service, Murdoch Children's Research Institute, Royal Children's Hospital, Department of Paediatrics, University of Melbourne, Melbourne, Australia.
authors.forename: Tiong Y
authors.initials: TY
authors.lastname: Tan
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Wanling
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: So Lun
authors.initials: SL
authors.lastname: Lee
authors.affiliation: Department of Obstetrics and Gynecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Wing Fai
authors.initials: WF
authors.lastname: Tang
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Winnie W Y
authors.initials: WW
authors.lastname: Tso
authors.affiliation: Department of Obstetrics and Gynecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Elizabeth T
authors.initials: ET
authors.lastname: Lau
authors.affiliation: Department of Obstetrics and Gynecology, Queen Mary Hospital, Hong Kong Special Administrative Region, China.
authors.forename: Anita S Y
authors.initials: AS
authors.lastname: Kan
authors.affiliation: Department of Obstetrics and Gynecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Mary H
authors.initials: MH
authors.lastname: Tang
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: Department of Paediatrics and Adolescent Medicine, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China; Department of Obstetrics and Gynecology, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Brian H Y
authors.initials: BH
authors.lastname: Chung
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D000293:Adolescent; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D002675:Child, Preschool; D002658:Developmental Disabilities / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D019468:Disease Management; D019317:Evidence-Based Medicine; D005260:Female; D005820:Genetic Testing; D006723:Hong Kong; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010372:Pediatrics; D055815:Young Adult