Aims: Array comparative genomic hybridization (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. Although array CGH offers a high diagnostic
yield, the majority of patients tested do not show any copy number variations (CNV).
Our study aimed at both, enlarging the phenotype of chromosomal microaberrations and
delineating clinical criteria, which may help separating patients with from those
without CNV.
Methods: We performed a retrospective review of clinical and array CGH data of 342 children
with unexplained DD/ID. We compared these data with previously reported microaberrations
and compared the phenotypic features of patients with clinical significant CNV with
those of patients without any CNV.
Results: Array CGH detected CNVs in 21% (72/342) of patients. Approximately two thirds (45/72)
of CNVs represented well-known microaberration syndromes and unbalanced translocations,
corresponding to an overall diagnostic yield of 13% (45/342). Most of the remaining
CNVs were previously unreported and of uncertain clinical significance. Congenital
anomalies, especially heart defects, as well as primary microcephaly, short stature
and failure to thrive were clearly more frequent in children with chromosomal microaberrations
compared to children with normal array CGH results.
Conclusion: In patients with unexplained DD/ID, array CGH will more probably detect a significant
CNV if any congenital anomaly, especially a congenital heart defect, or a disturbance
of somatic growth, including primary microcephaly, acquired short stature, or poor
weight gain, is part of the patient's phenotype.
Developmental delay - intellectual disability - array CGH - CNV - chromosomal microaberrations
- microdeletion and microduplication syndromes
