Authors' recommendations: Current guidelines for early assessment of DD/MR and for ASD recommend genetic evaluation for those cases that cannot be readily diagnosed from clinical characteristics or other specific tests. Conventional cytogenetic analysis (e.g., G-banded karyotype, specific FISH assays, and subtelomeric screening) has been routinely used for many years but has low resolution and low diagnostic yield. aCGH specifically detects CNVs, which account for the majority of genomic abnormalities currently detectable by conventional cytogenetic testing. aCGH does not detect balanced translocations or inversions, which account for a minority of clinically important genomic abnormalities. However, aCGH has shown that a substantial proportion of apparently balanced translocations by conventional methods contain submicroscopic deletions (i.e., are actually unbalanced). CGH arrays have the advantage of greatly improved resolution, which allows detection of smaller, clinically significant genomic abnormalities not detectable by conventional assays (improving diagnostic yield), and more exact locus definition of conventionally detectable abnormalities (improving information for genotype-phenotype correlation). While aCGH technology is relatively new, the results are conceptually similar to those obtained by conventional methods, and should be evaluated as an extension of those methods. The results of neither conventional cytogenetic evaluation nor of aCGH evaluation have been systematically studied for impact on patient outcomes other than diagnostic yield, which is an intermediate outcome. Impact of testing on the kinds of outcomes that matter to the patient and family has been directly addressed in very few studies. Thus, it is not possible to draw evidence-based conclusions regarding the clinical utility of aCGH genetic evaluation. The same may also be said of conventional cytogenetic evaluation. Expert consensus and clinical guidelines state that genetic information is of value because it establishes a causal explanation that is helpful to families. It is suggested that such genetic information avoids additional consultations and various types of diagnostic tests, assists with early and improved access to community services that may ameliorate or improve behavioral and cognitive outcomes, provides estimates of recurrence rates to better guide reproductive decision-making, and enables an understanding of prognosis and future needs. However, little evidence supports these outcomes. aCGH technology is rapidly evolving and different kinds of arrays with different capabilities of detecting genomic abnormalities are clinically available from different laboratories; it is up to the ordering physician to know the limits of the particular technology employed by the laboratory. Some have called for broader efforts to standardize protocols, define quality criteria for successful analysis, and develop reporting guidelines; in addition, a national multicenter trial to address accuracy, indications, and efficacy has been suggested. Currently, a consortium of scientists from academic cytogenetic laboratories have agreed to develop a uniform, evidence-based “Molecular Karyotype” and shared national database to accumulate data on pathogenic versus benign deletions and duplications in the human genome. Such cooperative efforts should lead to more comparable results across platforms, more complete databases to aid in individual results interpretation, more uniform reporting, and more rapid accumulation of genotype-phenotype correlation information for future reference.

Project Status: Completed

URL for project: http://www.bcbs.com/blueresources/tec/vols/23/acgh-genetic-evaluation.html

Year Published: 2008

English language abstract: An English language summary is available

Publication Type: Not Assigned

Country: United States

Organisation Name: BlueCross BlueShield Association

Contact Address: BlueCross BlueShield Association, Technology Evaluation Center, 225 North Michigan Ave, Chicago, Illinois, USA. Tel: 888 832 4321

Contact Name: tec@bcbsa.com

Contact Email: tec@bcbsa.com

Copyright: BlueCross BlueShield Association (BCBS)