The identification of microdeletion syndromes and other chromosome abnormalities: Cytogenetic methods of the past, new technologies for the future

Abstract

Chromosome analysis is an important diagnostic tool in the identification of causes of mental retardation, developmental delay, and other developmental disabilities. Cytogenetic approaches have revealed the chromosomal basis of a large number of genetic syndromes. The recent use of microarray‐based comparative genomic hybridization (array CGH) has accelerated the identification of novel cytogenetic abnormalities. We present the results of array CGH in 8,789 clinical cases submitted for a variety of developmental problems. Of these cases, 6.9% showed clinically relevant abnormalities, 1.2% showed benign copy‐number variants (polymorphisms), 2.5% showed recurrent alterations of unclear clinical significance—many of which are likely to be polymorphisms—and 1.4% showed novel alterations of unclear relevance. Although cytogenetic methods, including array CGH, have great potential for identifying novel chromosomal syndromes, this high‐resolution analysis may also result in diagnostic challenges imposed on laboratories and clinicians regarding findings of unclear clinical significance.