Array CGH in patients with developmental delay or intellectual disability: are there phenotypic clues to pathogenic copy number variants?

Clin Genet. 2013 Jan;83(1):53-65. doi: 10.1111/j.1399-0004.2012.01850.x. Epub 2012 Feb 21.

Abstract

Array comparative genomic hybridization (array CGH) is now widely adopted as a first-tier clinical diagnostic test in individuals with unexplained developmental delay/intellectual disability (DD/ID) and congenital anomalies. Our study aimed at enlarging the phenotypic spectrum associated with clinically relevant copy number variants (CNVs) as well as delineating clinical criteria, which may help separating patients with pathogenic CNVs from those without pathogenic CNVs. We performed a retrospective review of clinical and array CGH data of 342 children with unexplained DD/ID. The phenotypic features of patients with clinically significant CNV were compared with those without pathogenic CNVs. Array CGH detected pathogenic CNVs in 13.2% of the patients. Congenital anomalies, especially heart defects, as well as primary microcephaly, short stature and failure to thrive were clearly more frequent in children with pathogenic CNVs compared with children with normal array CGH results. Thus, we assume that in patients with unexplained DD/ID, array CGH will more probably detect a significant CNV if any of these features is part of the patient's phenotype.

MeSH terms

  • Adolescent
  • Child
  • Comparative Genomic Hybridization / methods*
  • DNA Copy Number Variations / genetics*
  • Developmental Disabilities* / diagnosis
  • Developmental Disabilities* / genetics
  • Failure to Thrive / genetics
  • Failure to Thrive / physiopathology
  • Female
  • Humans
  • Infant
  • Intellectual Disability* / genetics
  • Intellectual Disability* / physiopathology
  • Male
  • Microcephaly / genetics
  • Microcephaly / physiopathology
  • Phenotype
  • Retrospective Studies