Abstract

PURPOSE:

Array-based comparative genomic hybridization is increasingly being used in patients with learning disability, in addition to existing cytogenetic techniques. This paper reports the results of an evaluation of this emerging technology and discusses the challenges faced in conducting the evaluation.

METHODS:

Systematic review and meta-analysis of studies investigating patients with learning disability and dysmorphic features in whom conventional cytogenetic analysis has proven negative. Conventional indices of clinical validity could not be calculated, and we use an alternative, based on the extent to which array-based comparative genomic hybridization met its clinical objectives.

RESULTS:

Seven studies (462 patients) were included. The overall diagnostic yield of causal abnormalities was 13% (95% confidence interval: 10-17%; heterogeneity test statistic I = 0%), and the overall number needed to test was eight (95% confidence interval: 6-10). The false-positive yield of noncausal abnormalities ranged from 5% to 67%, although this range was only 5% to 10% in six of the studies.

CONCLUSION:

Although promising, there is insufficient evidence to recommend introduction of this test into routine clinical practice. A number of important technical questions need answering, such as optimal array resolution, which clones to include, and the most appropriate platforms. A thorough assessment of clinical utility and cost-effectiveness compared with existing tests is also required.